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C.P. Belani
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ED 10 - Controversies in Stage IIIA Disease (ID 10)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 4
- Moderators:C.P. Belani, E. Vokes
- Coordinates: 9/09/2015, 14:15 - 15:45, 201+203
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ED10.01 - Staging and Decision Making in Patient Selection-Surgery (ID 1810)
14:20 - 14:40 | Author(s): K. Suzuki
- Abstract
- Presentation
Abstract:
There are two clinical trial investigating the role of surgery in stage IIIA NSCLC.
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ED10.02 - Multiple Modality Choices: Combinations, Sequences, Subsets (ID 1811)
14:40 - 15:00 | Author(s): K. Albain
- Abstract
- Presentation
Abstract not provided
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ED10.03 - Induction Chemotherapy as an Investigational Strategy (ID 1812)
15:00 - 15:20 | Author(s): W.E.E. Eberhardt
- Abstract
- Presentation
Abstract:
Introduction: Standard treatment of stage IIIA non-small-cell lung cancer consists of definitive concurrent chemoradiotherapy (CTx/RTx) protocols. Based on the broad heterogeneity of stage IIIA alone, there are selected patients (single mediastinal lymph node involvement, IIIA3 Robinson) where induction chemotherapy (CTx) followed by definitive surgery may be an alternative and valid approach preferably to test within prospective clinical trials with a close documentation of the toxicity/efficacy ratio. Patients and Methods: The medical literature (PUBMED) was reviewed looking for the search terms “induction chemotherapy“ and “stage III“ and “non-small cell lung cancer“. Furthermore large clincal trials were added that had been presented at important clinical conferences such as ASCO, WCLC and ESMO. Prospective phase-III clinical trials and prospective phase-II clinical trials were examined and cathegorized for efficacy and outcome parameters. We looked specifically for general patterns in the reporting of clinical trials results. Results: General outcome parameters for efficacy that have been reported were: 1) objective response rates 2) overall survival (median) 3) progression-free survival rates 4) complete resection rates (R0-resection) 5) pathological complete response rates (pCR) in the primary tumor and 6) pathological complete response rates (pCR) in the mediastinum. On the other hand important benchmarks for toxicity were 1) grade 3 and grade 4 maximum toxicity rates during induction 2) perioperative toxicity rates grade 3 and 4 3) treatment related death rates. Very few investigations have looked at patient reported outcome parameters such as symptom improvement or quality of life evaluation during the complete treatment protocol. Several groups have tried to improve outcome data by the use of 1) three-drug regimen as induction treatment 2) second- and third-generation platinum-based combinations 3) introduction of new molecular targeted agents (VEGF, EGF-R etc) especially looking closely at the pathological complete response rates induced by induction therapy 4) inclusion of different radiation schemas within a concurrent or sequential preoperative application protocols. Several reported trials have also tried to alternatively give a definitive CTx/RTx protocol with increased radiation doses and have not included a definitive surgical approach. These studies could not report data on pathological responses and some have alternatively looked at FDG-PET response to induction therapy as a surrogate marker for pathological response. Currently the treatment protocols with the highest reported pathological response (pCR) rates were based on cisplatinum and taxane (paclitaxel and docetaxel) combinations and induction protocols including concurrent cCTx/RTx regimen were those with the highest pathological efficacy in the mediatinum as well as in the primary tumor. Conclusions and Outlook: With the existing broad heterogeneity in patient selection within the different clinical studies performed it is currently difficult to give an overall recommendation about the most optimal treatment approach in this setting of stage IIIA NSCLC. Induction CTx could potentially serve as a backbone for including new treatment principles (eg. molecular targeted agents, immunotherapy, CTx/RTx protocols) into these multimodality treatment protocols and closely monitoring outcome by translational investigations and pathological response evaluations.
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ED10.04 - Case Presentation (ID 1813)
15:20 - 15:40 | Author(s): K. Kernstine
- Abstract
- Presentation
Abstract not provided
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MINI 15 - Chemotherapy Developments for Lung Cancer (ID 128)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 15
- Moderators:L. Crinò, C.P. Belani
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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MINI15.01 - A Phase I/II Study Evaluating the Combination of Resminostat and Docetaxel for Platinum-Pretreated NSCLC (ID 700)
16:45 - 16:50 | Author(s): A. Horiike, T. Takahashi, H. Nokihara, N. Yanagitani, H. Kenmotsu, Y. Fujiwara, Y. Tambo, S. Kanda, M. Nishio, T. Tamura
- Abstract
- Presentation
Background:
Resminostat, an oral hydroxamate-type inhibitor of class I and II histone deacetylases, has shown a broad spectrum of anti-tumor activity against human cancer cell lines, and synergetic or additive effects in combination with docetaxel in non-small cell lung cancer (NSCLC) cell lines. We initiated a phase I/II study to evaluate the safety and efficacy of combining resminostat and docetaxel in patients (pts) with NSCLC pretreated with platinum-based therapy. The purpose of the phase I portion was to evaluate dose-limiting toxicities (DLTs) in the first cycle, estimate the maximum tolerated dose (MTD) of resminostat when administered in combination with docetaxel, and determine the recommended dose (RD) for the phase II portion. Here, we report the results of the phase I portion.
Methods:
NSCLC pts with failure of a platinum-based therapy were eligible for the study. Patients were treated with docetaxel on day 1 and resminostat on days 1 to 5 every 21 days. Phase I was an open-label, 3+3 cohort, dose-escalation study. While the docetaxel dose was fixed at 75 mg/m[2], the resminostat dose was escalated from 400mg (Dose Level 1: DL1) to 600 mg (DL2). DLT was defined as follows: grade 4 thrombocytopenia, grade 4 neutropenia lasting >7 days, febrile neutropenia lasting >3 days, and any other clinically significant grade 3/4 non-hematological toxicity.
Results:
A total of 9 pts (DL1: 3 pts, DL2: 6 pts) were enrolled in the phase I portion: male/female, 6/3; median age, 60 yr (50-71 yr); histologically proven adenocarcinoma/squamous cell carcinoma, 7/2; performance status, 0/1 in 7/2 pts. No DLTs were observed at DL1 or DL2. The most frequent grade 3/4 adverse events in any cycle were neutropenia (8 pts, 88.9%), leukocytopenia (8 pts, 88.9%), and febrile neutropenia (4 pts, 44.4%). These events were transient and resolved prior to the next cycle. No pharmacokinetic (PK) interaction between resminostat and docetaxel was observed. A partial response was observed in 1 pts (DL1) and stable disease in 3 pts (DL2).DL1 N=3 DL2 N=6 PK parameters (Geometric Mean) Resminostat Docetaxel Resminostat Docetaxel C~max ~(ng/mL) 3,010 2,840 5,610 3,140 T~max ~(h) 1.78 1.00 1.47 1.03 AUC~inf~(h∙ng/mL) 11,800 3,030 25,500 3,280 t~1/2~ (h) 2.98 8.21 3.02 8.73
Conclusion:
The combination of resminostat and docetaxel was tolerable up to DL2 (docetaxel 75 mg/m[2], resminostat 600 mg); the MTD was not reached. Dose Level 2 was determined as the RD for the phase II portion of this study, which is currently ongoing.
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MINI15.02 - NEJ016: Phase II Study of CBDCA and Weekly PTX plus BEV Followed by BEV for Highly Selected Elderly Non-Squamous NSCLC Patients (ID 977)
16:50 - 16:55 | Author(s): O. Yamaguchi, S. Miura, M. Maemondo, A. Iwashima, T. Harada, S. Sugawara, K. Kobayashi, A. Inoue, T. Nakagawa, Y. Takiguchi, H. Watanabe, M. Seike, T. Ishida, M. Terada, A. Gemma, H. Yoshizawa
- Abstract
- Presentation
Background:
It is considered that there is a population of “fit-elderly” patients, but how to select this population is undetermined. Two-drug regimen consisted of carboplatin (CBDCA) + weekly paclitaxel (PTX) in elderly patients with non-small cell lung cancer (NSCLC) was reported to be active but to have 4.4% of toxic deaths. When considering to add bevacizumab (BEV) to the two-drug regimen, meta-analysis of BEV-related adverse events taught that congestive heart failure (CHF) and arterial thromboembolic events increased in elderly patients. In this phase II study, we employed exclusion criteria of having both congestive heart failure (CHF) and diabetes mellitus (DM), which relates to arterial thromboembolism.
Methods:
Elderly (≥70 years old) patients with chemotherapy-naive, stage IIIB/IV or recurrent non-squamous NSCLC, ECOG-PS 0-1, measurable target lesion, and adequate organ functions were eligible for this study. Pts with CHF (i.e. those with brain natriuretic peptide (BNP) ≥ 100 pg/ml and ejection fraction (EF) ≤ 50%) and with DM (i.e. those with HbA1c ≥ 7.0%) were excluded. Treatment included CBDCA at AUC 5 on day 1, PTX at 90 mg/m[2] on days 1 and 8, and BEV at 15 mg/kg on day 1 of each 21-day cycle for up to 4 cycles, followed by maintenance BEV.
Results:
Thirty-six eligible patients (14 male, 22 female; median age, 75 years) were enrolled between February 2012 and September 2014. Fifteen and 21 patients had ECOG-PS of 0 and 1, respectively. The median number of CBDCA + weekly-PTX + BEV treatment cycles received was 4, and that of BEV maintenance dosing was 5. Grade 3/4 non-hematological and hematological toxicities were observed in 13 (36.1%) and 20 pts (55.6%), respectively. The most common grade 3/4 AEs included neutropenia (52.8%), hypertension (11%), anemia (8.3%), and infection (8.3%). No fatal AE was observed. The response rate, the primary endpoint of this study, was 69.4% (95% CI = 51.9–83.7), and median progression free survival was 9 months.
Conclusion:
CBDCA + weekly PTX + BEV followed by BEV was a feasible and effective first-line regimen for selected elderly non-squamous NSCLC patients. BNP, EF, and HbA1c may aid in selecting “bevacizumab-fit” elderly patients. Clinical information: UMIN000006622.
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MINI15.03 - Phase I & II Studies of the Decitabine-Genistein Drug Combination in Advanced Solid Tumours (ID 1091)
16:55 - 17:00 | Author(s): E. Kassouf, M. Tehfe, M. Florescu, D. Soulieres, B. Lemieux, J.M. Ayoub, D. Charpentier, L. Yelle, L. Daigneault, P. Colin, R.L. Momparler, I. Plante, G. Lassonde, M.R. Charbonneau, N.J. Raynal, N. Blais
- Abstract
- Presentation
Background:
The combination of epigenetic drug decitabine with genistein, a natural isoflavone, produces synergistic responses in preclinical studies with particular activity shown in lung cancer cell lines. Our phase I dose-escalation study of decitabine with a fixed dose of genistein to treat advanced solid tumor was followed by a phase II study in advanced lung cancer patients.
Methods:
In phase I, decitabine was administered over 10-hours at increasing doses (60, 120, 240 mg/m[2]) with continuous administration of genistein 300 mg/day orally. The MTD was 120 mg/m[2] with neutropenia as DLT. Decitabine at 120 mg/m[2 ]and genistein produced plasma levels of 0.62±0.06 µM and 8.5±5.6 µM, respectively.
Results:
The drug combination was well tolerated and produced stable disease for more than 6 months (7-14 months) in 5/10 patients. One gastric cancer patient had a 50% reduction in tumor burden after 6 months of therapy. Stable disease was also achieved in patients with desmoplastic small round cell tumor, oncocytic carcinoma, follicular thyroid carcinoma and bladder cancer. The phase II study was focused on nine patients with non-small cell lung cancer refractory to 3-4 lines of therapy. Eight progressed within the first radiologic evaluation at week 6. One NSCLC patient remains on therapy with SD after 3 months of treatment. A total of 60 adverse events were reported during the study with all patients experiencing at least one AE. Grade 3 & 4 treatment related toxicities were observed in 6/9 patients (66%) : neutropenia (4) anemia (2) febrile neutropenia (1) and hypertension (1).
Conclusion:
This combination of genistein with decitabine was well tolerated in advanced patients with solid tumors. The activity of the combination seen in some patients with tumors of more indolent biology was modest in the phase II cohort of heavily pretreated NSCLC patients. The efficacy profile observed in this trial suggests that tumors with slower tumor kinetics might benefit more from this type of epigenetic therapy.
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- Abstract
- Presentation
Background:
Endostar [TM ](rh-endostatin, 7.5mg/m[2], 3-hour intravenous infusion (IV) daily for 14 days) was approved by Chinese FDA for treatment of advanced NSCLC in 2005. Considering continuous intravenous infusion (CIV) may be a more favorable way to deliver Endostar, we designed the phase I study to evaluate pharmacokinetics, tolerability and efficacy of Endostar CIV at different doses combined with pemetrexed and carboplatin in untreated advanced non-squamous NSCLC patients.
Methods:
In phase Ia, 19 patients were assigned to 4-6 cycles (21 days/cycle) of pemetrexed (500mg/m[2], day 1), carboplatin (AUC 5, day 1), and CIV Endostar from day 2 to day 21 at doses of 7.5mg (8 patients), 15mg (6 patients), 30mg (5 patients) /m[2]/d, respectively. Serum samples were obtained 0h、1h、2h、4h、8h、24h、48h、72h、96h、120h、122h、124h、128h、132h and 144h after the Endostar infusion. In phase Ib, another 21 patients received CIV Endostar at doses of 7.5mg (10 patients) or 15mg (11 patients) /m[2]/d with pemetrexed + carboplatin.
Results:
The AUC~0-120h~ of Endostar 7.5mg/m[2] CIV and 7.5mg/m[2] 3-hour IV daily were comparable (12.6±7.6 vs 13.3±8.8 ug/mL × hour). C~max~ (ng/ml) (7.5mg: 152.4±83.7; 15mg: 287.2±122.6; 30mg: 398.2±52.6) and AUC~0-120h~ (ug/mL × hour) (7.5mg: 12.6±7.6; 15mg: 21.2±10.8; 30mg: 33.4±8.5) were linear with dose. In phase Ia, the most common adverse events were anemia (78.9%, G3/4 10.5%), neutropenia (68.4%, G3/4 31.6%), thrombocytopenia (63.2%, G3/4 10.5%), LDH increase (47.4%), aminotransferase increase (42.1%), and supraventricular arrhythmia (26.3%). No grade 3 or 4 non- hematologic adverse event was observed. The incidence of supraventricular arrhythmia in 30mg cohort (40%) was higher than the other two cohorts. Thus 30mg cohort was excluded in Ib phase. Totally, 15 patients in 7.5mg cohort and 17 patients in 15mg cohort were evaluable for treatment response. The DCR and ORR were 80.0% and 60.0% in 7.5mg cohort, 94.1% and 76.5% in 15mg cohort, respectively.
Conclusion:
The pharmacokinetics of Endostar CIV and daily IV were comparable. At doses of 7.5mg and 15mg/m[2]/d, Endostar CIV was well tolerated with encouraging anti-tumor efficacy. Increasing dose of Endostar might lead to better response.
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MINI15.05 - Discussant for MINI15.01, MINI15.02, MINI15.03, MINI15.04 (ID 3344)
17:05 - 17:15 | Author(s): G.D.L. Lopes Júnior
- Abstract
- Presentation
Abstract not provided
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MINI15.06 - Impact of Three and Further Lines in Advanced Non-Small Cell Lung Cancer Patients According to Molecular Profile: A Retrospective Analysis (ID 2919)
17:15 - 17:20 | Author(s): E. Carcereny, T. Moran, M.D.L.L. Gil, I. Teruel, L. Vila, M. Hardy-Weber, A. Estival
- Abstract
- Presentation
Background:
There is little evidence supporting the efficacy of third-line systemic therapy in non-small cell lung cancer (NSCLC) patients (p) with advanced (a) disease, except for erlotinib, and its role is unclear in unselected population. Nonetheless, further-line chemotherapy(CT) is frequently offered in daily clinical practice. We retrospectively analyzed the clinical, pathological characteristics and outcomes of p with aNSCLC who received >3 CT regimens to identify subsets of patients more likely to benefit. The presence of underlying molecular alterations has also been evaluated.
Methods:
The study included data from all consecutive p diagnosed with aNSCLC in our Institution from January 2008 to December 2013. Median overall survival (mOS) and progression free survival (PFS) were evaluated with Kaplan-Meier curves and groups were compared using the Log-rank test. Variables analyzed included p tumor and treatment characteristics. Overall response rate(ORR) was calculated according to the RECIST criteria.
Results:
A total of 486 p were included .175 p (36%) received >3 lines (group3+). Table 1 summarized p characteristics. Group 3+included more females (35.4%vs22.8%; p= 0.0041),younger p (58.9vs61.9;p =0.0016), more never-smoker p (26.9%vs18%;p=0.015), less lung (10.9%vs22.2%;p= 0.0020) and heart (4%vs11.6%;p=0.0020) comorbidities, a higher proportion of molecular alterations (EGFR/ALK) (25.7%vs12.9%; p= 0.0005), more adenocarcinoma (68.6%vs55%;p=0.0045) and less brain metastasis (14.3%vs23.5%;p=0.018). ORR to first line was higher in group 3+ (45.8%vs 29%;p=0.0009). 82.3% non-squamous histology were tested for at least one molecular alteration. There were no differences in PFS between both groups. The mOS of p in group 3+ was longer [24.3 m vs. 7.7 m, p<0.0001)], including p with EGFR/ALK/ROS1 wild-type or unknown [21.6 m vs. 7.4 m, p<0.0001) ]. OS was also longer in the group 3+ harboring a molecular alteration [32.2 m vs 12.7m;p=0.0002]. In the univariate analysis the presence of a molecular alteration were related to longer PFS. In univariate analysis having received >3, female gender, age<65 and the presence of molecular alterations were associated with longer OS. In the multivariate analysis >3 therapeutic lines and the presence of molecular alterations were related to longer OS.
Conclusion:
P treated with >3 systemic treatments were more likely to respond better, progress later and live longer. This better prognosis could be related to the presence of molecular alteration. However p without or unknown molecular alteration could benefit from receiving subsequent lines.
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MINI15.07 - Prognostic Importance of Pretreatment Sodium Levels in Patients of NSCLC Treated with Pemetrexed-Platinum Doublet Chemotherapy (ID 2926)
17:20 - 17:25 | Author(s): M. Nookala Krishnamurthy, V. Gota, K. Doshi, B. Shriyan, A. Joshi, K. Prabhash, V. Noronha
- Abstract
- Presentation
Background:
A recent study has shown pretreatment sodium levels to be a predictive and prognostic marker in NSCLC patients treated with erlotinib. The objective of this study was to evaluate the prognostic impact of pretreatment sodium levels on progression free survival (PFS) and overall survival (OS) in patients of NSCLC treated with pemetrexed-platinum doublet chemotherapy.
Methods:
Stage IIIB/ IV NSCLC patients aged ≥ 18 years treated between January 2011 to November 2014 at our centre were included in this retrospective study. Patients received pemetrexed 500 mg/m[2] with either cisplatin 75 mg/m[2 ]or carboplatin (AUC 5) on day 1 of a 21 day cycle for 6 cycles followed by maintenance pemetrexed till progression. Electronic medical record (EMR) database of our hospital was used to retrieve demographic data, pretreatment sodium levels, PFS and OS data. LSS was defined as serum sodium < 136mEq/L. Survival analysis was performed using Kaplan-Meier curves and compared between LSS and normal serum sodium (NSS) groups using Log-Rank test and proportional hazard model.
Results:
Figure 1Data was available for 256 patients (M/F = 172/84) with median age of 53 (25-79) years. Majority had ECOG PS of 1 (0 = 34, 1 = 172, 2 = 44, 3 = 6). Stage IIIB = 24 (9%), stage IV = 232 (91%). Pretreatment LSS was observed in 75 (29%) patients while 181 (71%) had NSS. Median duration of follow-up was 17 months. Patients with NSS had significantly longer PFS (10.7 vs. 7.4 months; P < 0.05) and OS (17.6 vs. 13.4 months; P < 0.05) compared to LSS group. Cox-proportional hazard model has shown LSS was an independent prognostic biomarker for poor survival (P < 0.05).
Conclusion:
Pretreatment serum sodium level is an important prognostic marker in stage IIIB/ IV NSCLC patients. The simple possibility of testing coupled with low cost makes it an attractive marker to implement in clinical practice.
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MINI15.08 - A Phase II Study of Pemetrexed plus Carboplatin Followed by Maintenance Pemetrexed in Elderly Patients with Advanced Non-Squamous NSCLC (ID 2453)
17:25 - 17:30 | Author(s): M. Tamiya, A. Tamiya, H. Kaneda, K. Nakagawa, K. Goto, K. Yoh, H. Okamoto, T. Shimokawa, H. Tanaka, T. Abe, H. Daga, K. Takeda, T. Hirashima, S. Atagi
- Abstract
- Presentation
Background:
Non-small-cell lung cancer (NSCLC) accounts for >80% of all lung cancers, and the risk of lung cancer clearly increases with advancing age. Because of the progressive aging of population, the number of elderly patients with NSCLC is increasing and the desease is becoming an increasing public health problem worldwide. We previously reported a phase I study that recommended a dose of carboplatin (Cb, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m[2]) for elderly (≥75-years-old) patients with non-squamous NSCLC. Furthermore, PEM maintenance therapy, following the combination therapy, was also found to be well tolerated. Therefore, we conducted a multicenter phase II trial to evaluated the efficacy and safety of Cb (area under the curve = 5) plus PEM (500 mg/m[2]) followed by maintenance PEM for elderly (≥75-years-old) patients with non-squamous NSCLC.
Methods:
Treated patients received 4 courses of Cb plus PEM, followed by maintenance PEM, without showing disease progression or severe toxicities. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression free survival (PFS), response rate (RR), and safety.
Results:
Thirty four patients were enrolled between June 2012 and May 2013. All patients had an ECOG performance status 0 or 1, and adenocarcinoma. The median patient age was 77 years (75-84 years). Twenty four patients were male and ten patients were female. Three patients harbored activating epidermal growth factor recepter mutation (exon19 or 21). The median observation time was 22.7 months. In clinical outcome, the overall RR was 41.2%, and the disease control rate was 85.3%. No patient showed a complete response, 14 showed partial responses, 15 showed stable disease, 4 showed disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8%. The median PFS for all patients was 5.7 months (95% confidence interval, 3.3–8.5 months), whereas the median OS was 20.5 months (95% confidence interval, 7.8–25.4 months). The 1-year OS rate was 58.0%. In adverse events (total phase of this study), hematological adverse events ≥grade 3 were leucopenia (in 23.5% of patients), neutropenia (55.9%), anemia (35.3%), and thrombocytopenia (20.6%), and major non-hematological adverse events ≥grade 3 were febrile neutropenia (in 8.8% of patients), increased levels of aminotransferase (5.9%), infection (23.5%), and anorexia/fatigue (5.9%). There was 1 treatment-related death due to interstitial lung disease.
Conclusion:
The combination of Cb plus PEM followed by maintenance PEM was effective and reasonably well tolerated in chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC. This data was promising and valuable to conduct the phase III study compared with docetaxel (DOC) monotherapy in the first-line setting. Now, the phase III trial compared Cb plus PEM followed by maintenance PEM with DOC for chemotherapy-naïve elderly (≥75-years-old) patients with non-squamous NSCLC (JCOG1210/WJOG7813L: UMIN000011460) is ongoing and the result is warranted. Clinical trial information: UMIN000004810
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MINI15.09 - Bayesian Network Meta-Comparison of Maintenance Treatments for Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients (ID 636)
17:30 - 17:35 | Author(s): G. De Lima Lopes, P.S. Tan, S. Acharyya, M. Bilger, B. Haaland
- Abstract
- Presentation
Background:
Recent trials suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced NSCLC. However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis (NMA) of current evidence assessing relative efficacies of maintenance options in unselected populations, as well as in subgroups determined by EGFR mutation, histology, and response to induction.
Methods:
PubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analyzed in a Bayesian hierarchical model. The primary and secondary outcomes, Overall Survival (OS) and Progression Free Survival (PFS), respectviely, were evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratios with 95% credible intervals, in an unselected population, as well as by EGFR mutation status, histology, and response to induction. Secondary outcomes were overall survival (OS) and adverse events.
Results:
Twelve trials evaluating eight maintenance treatments in 3,850 patients were included in NMA. Selected maintenance treatments showed substantial PFS and OS benefits with probabilities ≥99% and ≥92% respectively of outperforming no maintenance. Results suggest the following strategy for optimal OS and PFS: (i) switch to or continue pemetrexed or switch to anti-EGFR TKI for nonsquamous patients, (ii) continue gemcitabine for squamous patients, (iii) switch to docetaxel or continue gemcitabine for responders to previous induction, and (iv) switch to or continue pemetrexed or switch to anti-EGFR TKI for patients with stable disease post-induction.
Conclusion:
Maintenance treatments improve PFS and OS in good performance status patients with stage IIIb/IV NSCLC not progressing after first-line chemotherapy. Benefits are optimized by targeting specific maintenance treatments to selected patient groups guided by histology and response to previous induction.
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MINI15.10 - Discussant for MINI15.06, MINI15.07, MINI15.08, MINI15.09 (ID 3345)
17:35 - 17:45 | Author(s): L. Crinò
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
Pemetrexed and cisplatin (P-C) has become the standard 1st line chemotherapy in NSCLC patients with wild-type EGFR. The recommended drugs in the 2nd line are docetaxel, docetaxel plus ramucirumab, gemcitabine or EGFR TKIs. Gemcitabine and vinorelbine have good clinical efficacies and low toxicity profiles, so this two drug combination therapy is challenged for their clinical efficacy as 2nd line treatment. The optimal 2nd line chemotherapy following failure of 1st line P-C treatment in advanced NSCLC patients with wild-type EGFR is not yet defined. Therefore, we evaluated the optimal 2nd line chemotherapy in P-C non-responders with advanced NSCLC.
Methods:
We conducted a retrospective analysis of patients with stage IIIB or IV NSCLC who had been treated with P-C as a first line treatment from February 2010 to May 2014. Patients who had EGFR mutation or were on pemetrexed maintenance therapy were excluded. We compared the progression free survival, overall response rate and adverse effects of each regimen.
Results:
Among 110 patients, 52 were eligible for the study. 28 received EGFR TKI (gefitinib or erlotinib); 13 received docetaxel monotherapy; 11 received gemcitabine-vinorelbine (G-V) combination therapy. Median age was 64.5, 61 and 63 years, respectively. All patients showed adenocarcinoma type histology except two in docetaxel and G-V group with large cell type histology. Best response rates were 15.4% in docetaxel group, 18.1% in G-V group and 11% in EGFR TKIs group. Median progression free survival time was 62 days(95% CI 54-70) in EGFR TKIs group, 63 days (95% CI 30-96) in docetaxel group, and 83 days (95% CI 55-111) in G-V group (P=0.17). In pairwise comparisons, p-value was 0.54 for EGFR TKI versus docetaxel group, 0.08 for TKI versus G-V group, and 0.23 for docetaxel versus G-V group. There were no difference in progression-free survival and response rate among the groups. There was a higher rate of grade 3/4 neutropenia in the Docetaxel group.
Conclusion:
Despite the absence of statistical significance, there was a trend that G-V combination therapy had longer progression-free survival outcome compared to EGFR TKI or Docetaxel groups. G-V as well showed better toxicity profiles compared to Docetaxel group. A larger study is required to confirm the efficacy of cytotoxic chemotherapy, especially G-V, as a second line treatment in EGFR mutation negative NSCLC patients.
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MINI15.12 - Satisfaction with Therapy and the Relation with Quality of Life in Patients with Advanced NSCLC Receiving Chemotherapy (ID 2253)
17:50 - 17:55 | Author(s): S. Visser, M. De Mol, C. Cheung, N. Van Walree, J. Van Toor, B.L. Den Oudsten, B. Stricker, J.G. Aerts
- Abstract
- Presentation
Background:
In advanced non-small cell lung cancer (NSCLC) decisions regarding palliative treatment are based on tumor response, increasingly combined with patient reported outcomes, especially quality of life (QoL). However, considering treatment decisions in this manner ignores patients’ own opinion about (change in) QoL. A more patient-oriented view regarding therapy could offer valuable information in the process of shared decision-making about treatment initiation or continuation with chemotherapy. We assessed patients’ satisfaction with the received chemotherapy using the Cancer Therapy Satisfaction Questionnaire (CTSQ) in relation with QoL during treatment.
Methods:
In a prospective observational multi-center study, patients with stage IIIB or IV NSCLC receiving pemetrexed (PEM)-based chemotherapy as first or second line treatment were enrolled. Prior to and after four cycles of chemotherapy, patients completed the WHO Quality of Life-BREF (WHOQoL-BREF) and EORTC-Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), which both contain one item measuring overall QoL on a 1-5 and 1-7 scale, respectively. After four cycles patients also completed the CTSQ, which consists of 16 items scored on a 1-5 scale and is divided in three domains, including the domain satisfaction with therapy (SWT). Linear transformation of the domain score results in a score range 0-100, with a higher score representing a better treatment satisfaction. Items of special interest were Question 7 (Q7) “Chemotherapy was worth taking even with side effects”, Question 16 (Q16) “If given the choice again, would you decide to take this chemotherapy treatment” and Question 2 (Q2) “Chemotherapy would cure the cancer”. From all patients tumor response measurements were obtained according to RECIST 1.1.
Results:
Of the 88 patients receiving four cycles of PEM-based chemotherapy, 65 patients completed the WHOQoL-BREF, EORTC-QLQ-30 and the CTSQ. The majority of these patients had stage IV NSCLC (87.7%) and received PEM-based therapy as first line treatment (92.3%). Treatment resulted in stable disease (53.8%), partial response (40.0%) and progressive disease (6.2%). Eighteen patients often (13.8%) or always (13.8%) expected chemotherapy would cure the cancer. During therapy, overall QoL measured by WHOQoL-BREF increased (1.3±0.6), remained stable (0±0) and decreased (-1.4±0.7) in respectively 15 (23.1%), 30 (46.2%) and 20 (30.8%) patients. The SWT domain score (77.5±12.3 vs. 83.8±13.1) and single item scores Q7 (4.1±0.9 vs. 4.4±0.8) and Q16 (4.4±0.7 vs. 4.5±0.6) in patients with decrease vs. increase of overall QoL did not differ significantly between the groups (p> 0.05). Change in overall QoL measured by the EORTC-QLQ-C30 related to SWT, Q7 and Q16 showed similar results.
Conclusion:
Despite a decrease of QoL during chemotherapy, patients still consider the treatment as worth taking and would decide to receive the chemotherapy again. Since the majority of patients understand that the treatment has no curative intentions, it is unlikely that the satisfaction with treatment only reflects false expectations of cancer cure. Our results represent a group of patients who mainly established disease stabilization, which could have influenced our findings. In shared decision-making on palliative treatment, patients’ QoL cannot be used as a single decision criterion because it does not reflect patients’ satisfaction with treatment. This study is funded by ZonMw, the Netherlands
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MINI15.13 - An Evaluation of Chemotherapy Regimens in an Unselected Population of NSCLC Patients (ID 2314)
17:55 - 18:00 | Author(s): A.A. Badawy, S. Bae, S.C. Grant
- Abstract
- Presentation
Background:
Randomized clinical trials have demonstrated the benefits of chemotherapy in carefully selected NSCLC patients. How generalizable these results are to the general population of NSCLC patients, who often have multiple comorbidities that would have rendered them ineligible for licensing trials, is unresolved.
Methods:
The outcomes of unselected patients with stage IV NSCLC who did not participate in a clinical trial and who were treated with standard chemotherapy regimens (paclitaxel/carboplatin; gemcitabine/carboplatin; pemetrexed/carboplatin; paclitaxel/carboplatin/bevacizumab) as first line therapy between 2002 and 2012 at a tertiary teaching hospital were compared to the reported outcomes observed in the licensing trials supporting the use of these drug regimens.
Results:
Results are summarized in Table 1 Patients treated with three-weekly paclitaxel plus carboplatin at recommended dosages had a median progression free survival of 4.9 months for patients responding to this regimen and an overall survival of 13.1 months for responders vs 9.2 months for non-responders. In patients’ treated with gemcitabine plus carboplatin on a three or four week cycle the median progression free survival was 4.8 months for patients responding to the regimen and overall survival of 13 months for responders vs 8.9 months for non-responder group of patients. For patients receiving pemetrexed plus carboplatin the median progression free survival was 7.1 months for patients responding to the regimen with an overall survival of 15.5 months for responders vs 5.9 months for non-responders. Those patients’ treated with paclitaxel plus carboplatin plus bevacizumab the median progression free survival was 7.3 months for patients responding to treatment and overall survival was 16.7 months vs 14.6 months for those patients who did not respond to this regimen as initial treatment. Table I: Patient demographics and results for each regimenpaclitaxel and carboplatin N=105 Gemcitabine and carboplatin N=35 pemetrexed and carboplatin N=26 paclitaxel and carboplatin and bevacizumab N=28 Age 70> 15.2% 31.4% 26.9% 25.0% < 70 84.8% 68.6% 73.1% 75.0% Gender Male Female 64.8% 35.2% 51.4% 48.6% 57.7% 42.3% 60.7% 39.3% Smoker 89.2% 91.2% 84.6% 71.4% ECOG 0 12.6% 12.1% 8.7% 23.1% 1 68.9% 63.6% 47.8% 76.9% 2 17.5% 24.2% 43.5% 0.0% 3 1.0% 0.0% 0.0% 0.0% PFS (months) 4.9 4.8 7.1 7.3 OS (months) PR PD 13.1 9.2 13 8.9 15.5 5.9 16.7 14.6
Conclusion:
Progression free survival in an unselected population of NSCLC patients was similar to that reported in clinical trials supporting the approval of these drugs and regimens. The present analysis provides further support for the use of combination chemotherapy in patients with stage IV NSCLC, including those who would have been ineligible for many clinical trials due to comorbidities. Further analysis is ongoing.
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MINI15.14 - The Role of Breath Sampling in Monitoring Response to Treatment in Lung Cancer (ID 2551)
18:00 - 18:05 | Author(s): I. Nardi Agmon, M. Abud-Hawa, O. Liran, N. Gai-Mor, M. Ilouze, A. Onn, J. Bar, R. Navon, D. Shlomi, H. Haick, N. Peled
- Abstract
- Presentation
Background:
The current available method to monitor response to treatment in lung cancer patient is by Computerized Tomography (CT) scans. However, time intervals between consecutive CT scans might be too long to allow early identification of treatment failure. The aim of this study is to examine the use of breath sampling as a tool for monitoring response to anti-cancerous treatment in patients with advanced lung cancer.
Methods:
In a prospective study, repeated exhaled breath samples were collected from patients with advanced lung cancer before and under systemic therapy. VOCs[1] profiles were determined by GC-MS[2] and nanomaterial-based array of sensors and correlated with response to therapy, assessed by CT scans as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). [1] Volatile Organic Compounds [2] gas-chromatography/mass-spectrometry
Results:
One hundred forty three breath samples were collected from 39 patients with stage III/IV lung cancer. GC-MS anaylsis identified 3 VOCs as significantly indicating PR/SD samples. One of them was also significantly discriminated between PR/SD and PD. Further, the NA-NOSE signals were able to alarm per a change in tumor response across therapy, i.e. indicating lack of further response to therapy, or developement of resistance to therapy. PR/SD was detected in a sensitivity of 93%, specificity of 85% and accuracy of 89% and ppositive/negative predictive values (PPV; NPV) of 86% and 92% respectively. PD was detected with 100% specificity and 92% accuracy, but the sensitivity was only 28%. The PPV and NPV were 100% and 91%, respectively. The achieved results indicate high reliability in predicting a progression of the disease and detecting patient's lack of response to treatment (i.e., PD).
Conclusion:
Breath analysis may serve as a serogate marker for response to systemic therapy in lung cancer. Such a monitoring tool can provide the oncologist with a quick and simple method to identify patient's response to anti-cancerous treatment in shorter intervals than currently available by CT scans.
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MINI15.15 - Discussant for MINI15.11, MINI15.12, MINI15.13, MINI15.14 (ID 3547)
18:05 - 18:15 | Author(s): P.J. Hesketh
- Abstract
- Presentation
Abstract not provided
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Author of
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HOD 01 - Highlights of the Previous Day: Treatment of Advanced, Localized and LocoRegional Disease and Small Cell, Thymoma, Mesothelioma (ID 240)
- Event: WCLC 2015
- Type: Highlights of the Day
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 07:00 - 08:00, Four Seasons Ballroom F1+F2
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HOD01.03 - Treatment of LocoRegional Disease (ID 3394)
07:30 - 07:45 | Author(s): C.P. Belani
- Abstract
Abstract not provided
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MINI 29 - Meta Analyses and Trial Conduct (ID 156)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:D. Morgensztern, M. Redman
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 2a-3b
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MINI29.01 - Squamous Cell Carcinoma of Lung in the United States: Analysis of the National Cancer Database (NCDB) (ID 2747)
18:30 - 18:35 | Author(s): C.P. Belani
- Abstract
Background:
Lung squamous cell carcinoma (SCC) is the second most common histological sub type of lung cancer and accounts for about 30% of all non-small cell lung cancers (NSCLC). We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the epidemiology, patterns of care, outcomes and temporal changes in incidence of SCC.
Methods:
The NCDB was queried from 1998 to 2011 for SCC using ICD-O-3 codes. Temporal changes in incidence were estimated in intervals (1998-1999, 2000-2003, 2004-2007, 2008-2011). The univariate association with covariates between SCC and other subtypes of NSCLC was assessed using Chi-square test or ANOVA. The univariate (UV) and multivariable analysis (MV) with OS were conducted by Cox proportional hazards model and log-rank tests. All statistical analyses were conducted using SAS Version 9.3.
Results:
A total of 435,358 pts with SCC were included in the analysis and accounted for 28% of all NSCLC pts in NCDB. Pt characteristics: median age 70 (18-90 yrs); males 64%; whites 87%; academic centers 27%; metro locations 78%; government insured 72%; Charlson/Deyo comorbidity score (CDS) 0 in 55% and ≥2 in 15%, and stage III/IV- 34/31%. Chemotherapy was used in 39% of pts, radiation in 46% and surgery in 32%. Approximately 19% of the pts did not receive any of the three treatments. Incidence of SCC decreased over time (35%, 28%, 26%, 27%) vs. increasing trend in non-SCC (65%, 72%, 75%, 72%); p<0.001). The trend was similar across all races and sex. SCC was associated with a higher co-comorbidity burden than non-SCC across all stages (CDS 0: 55% vs. 62%; CDS 1: 31% vs. 27%; CDS ≥2: 15% vs. 11%; p<0.001). SCC was associated with inferior 5 yr survival vs. non-SCC in all stages (stage I- 30% vs. 41%, stage II- 16% vs. 21%, stage III- 8.5% vs.10%, stage IV- 1.9% vs. 2.5% respectively; p<0.0001). The 1 yr survival in stage IV SCC is 19.6% vs. 22.2% in non-SCC (p<0.0001). Males had worse survival (HR 1.11 (1.09-1.13; p<0.001). Pts at community centers had worse survival vs. academic centers (HR 1.27 (1.23-1.30; p<0.001). An increasing trend in chemotherapy use was observed (31% in 1998 to 43% in 2011) vs. a decreasing trend in use of radiation (52% in 1998 to 46% in 2011) and surgery (32% in 1998 to 27% in 2011). Chemotherapy was received by 48% of patients with stage IV SCC. Chemotherapy use across other stages: 0/I- 18%, II- 46%, III- 60%. Males were more likely to receive any treatment (OR 1.12 (1.08-1.15); p<0.001). Pts that received any treatment had significantly better 5 year survival than those who did not receive any (20.3% vs. 3.3%, p<0.0001)
Conclusion:
SCC accounted for 28% of all cases of NSCLC in the United States, was associated with higher comorbidities and a significantly worse survival compared to non-SCC of the lung. Chemotherapy was used in only 48% of pts with stage IV SCC.
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ORAL 05 - Surgery (ID 97)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:P. Van Schil, F.(. Kong
- Coordinates: 9/07/2015, 10:45 - 12:15, 201+203
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ORAL05.05 - Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis (ID 2962)
11:48 - 11:59 | Author(s): C.P. Belani
- Abstract
Background:
Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the optimal approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society.
Methods:
The NCDB was queried from 2003-2011 for NSCLC pts diagnosed with stage IIIA-N2 disease and treated with chemotherapy and radiation (CRT). Data was extracted on patient demographics, tumor pathology, treatments and outcomes. Three cohorts of pts were studied - CRT only/no surgery (NS), CRT + lobectomy (L) and CRT + pneumonectomy(P). The univariate and multivariable analyses (MV) were conducted using Cox proportional hazards model and log rank tests. All analyses were performed using SAS Version 9.3.
Results:
A total of 29,584 pts were included in this analysis: NS-91.7%, L-7%, and P-1.5%. Pt characteristics: median age 66 years (yrs); males 56%; whites 86%; academic centers 27%; metro locations 78%; government insured 63%; Charlson/Deyo comorbidity score 0 in 66%. Pts < 60 yrs were more likely to receive TT- L (47%), P (60%) vs. NS (29%); p<0.001. Pts in academic centers were more likely to get TT than NS (42% vs. 25%). On MV analysis, L and P had significantly better survival vs. NS: HR 0.43 (0.38-0.48) and HR 0.57 (0.46-0.71) respectively; p <0.001. The median survival of L, P and NS were 44.5 m vs. 25.6 m vs. 15.7 m (p<0.001) and 5- year survival rates (SR) were 44% vs. 33% vs. 14% respectively. 30-day mortality was higher in P vs. L [7% vs. 2.6%; OR 0.26(0.16-0.45); p<0.001]. Pts with <2 lymph nodes (LN) had better survival than pts with >2 LNs in L (50% vs. 37%; 60m vs. 38.8m) but worse in NS (13.8% vs.16.4%; 15.3m vs.18.5m). On MV analysis of LNs, L had better survival than NS: HR 0.4 (0.35-0.46) in <2 LN pts and HR 0.56 (0.46-0.69) in ≥2 LN pts; p<0.001. In pts with <2 LN, L had better survival than P (60m vs. 25.5m; p<0.0001). L and P had better SR than NS in all ages: 48% vs.37% vs. 19% in ≤60 yrs; 42% vs. 30% vs.14% in 61-70 yrs, 36% vs.19% vs. 10% in >70 yrs.
Conclusion:
TT was utilized in less than 10% of pts with stage IIIA-N2 disease, suggesting high degree of pt selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.01 - A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin-Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients (ID 600)
10:45 - 10:56 | Author(s): C.P. Belani
- Abstract
- Presentation
Background:
The two most commonly used chemotherapy regimens deployed concurrently with thoracic radiation (RT) for patients with unresectable IIIA and IIIB non-small cell lung cancer (NSCLC) are carboplatin/paclitaxel (CP) and cisplatin/etoposide (CE). Because there are no prospective comparisons of these two regimens in this setting, we conducted a systematic review of published trials to compare outcomes and toxicities between CE and CP.
Methods:
Studies which enrolled stage III patients receiving RT with CP or CE were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase I, enrolled less than 10 pts, or included surgical resection. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2) software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), response rate (RR) and toxicities. Two-tailed T-test with a significance level of 0.05 was used for all comparisons.
Results:
3194 patients were included from 32 studies in the CE arm, and 3789 patients from 51 studies in CP. Baseline characteristics of patients on the CE arm versus CP arm were: median age 61 vs. 63 years, male 67.6% vs. 78%, squamous histology 39% vs. 40%, and median radiation dose 62 Gy vs. 63 Gy. There was no significant difference in response rates between CE and CP (65% vs. 56%, p =0.6), respectively. There was no significant difference in median progression free survival (11.5m vs. 9.3m p =0.2), overall survival (19.8m vs. 18.4m, p=0.48), 1-year survival rate (66% vs. 65%, p=0.8), or 3-year survival rate (31% vs. 25%, p=0.4) for CE vs. CP. CE was associated with higher grade 3/4 hematological toxicities than CP, such as neutropenia (53% vs. 23% p<0.0001), thrombocytopenia (14% vs. 6% p=0.001), anemia (16% vs. 8% p=0.06), as well as grade 3/4 nausea/vomiting (20% vs. 9% p=0.018), while rates of grade 3/4 pneumonitis and esophagitis were similar.
Conclusion:
CE and CP regimens were associated with comparable efficacy when used with concurrent radiotherapy for stage III unresectable NSCLC pts. The toxicity profile favored the CP regimen.
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ORAL 33 - ALK (ID 145)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:S. Gadgeel
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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ORAL33.03 - Updated Efficacy/Safety Data From the Phase 2 NP28761 Study of Alectinib in ALK+ NSCLC (ID 1261)
17:07 - 17:18 | Author(s): C.P. Belani
- Abstract
- Presentation
Background:
ALK gene rearrangements occur in approximately 3–6% of patients with non-small-cell lung cancer (NSCLC). Crizotinib has demonstrated efficacy in ALK+ NSCLC, however many patients experience systemic and/or central nervous system (CNS) disease progression within one year of treatment. Alectinib, a CNS-penetrant and highly selective ALK inhibitor, has shown preclinical activity in the CNS (Ou, et al. JTO 2013) and clinical efficacy in crizotinib-naïve (Ohe, et al. ASCO 2015) and pre-treated (Ou, et al. ASCO 2015; Gandhi, et al. ASCO 2015) ALK+ NSCLC patients. We will present updated efficacy and safety outcomes from the phase II NP28761 study (NCT01871805).
Methods:
North American patients ≥18 years of age with ALK+ NSCLC (by FDA-approved FISH test), disease progression following first-line crizotinib, and ECOG PS ≤2 were enrolled. Patients received oral alectinib (600mg) twice daily until progression, death or withdrawal. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) using RECIST v1.1. Secondary endpoints included investigator-assessed ORR; progression-free survival (PFS); quality of life (QoL); CNS response rate; disease control rate (DCR); and safety.
Results:
At data cut-off (24 October 2014), 87 patients were enrolled in the intent-to-treat population. Median age was 54 years; 74% had received prior chemotherapy; 60% of patients had baseline CNS metastases, of whom 65% (34/52) had prior brain radiation therapy. Median follow-up was 20.7 weeks. ORR by IRC was 48% (95% CI 36–60); median PFS was 6.3 months (Table 1). In patients with measurable CNS lesions at baseline (n=16), IRC CNS ORR was 69% (95% CI 41–89) and CNS DCR was 100% (complete response, 13%; partial response, 56%; stable disease, 31%). In patients with measurable or non-measurable CNS disease (n=52), IRC CNS ORR was 39% (95% CI 25–53) and 11 patients (21%) had complete CNS responses. The most common grade ≥3 AEs were elevated levels of blood creatine phosphokinase (8%), alanine aminotransferase (6%) and aspartate aminotransferase (5%); no GI toxicities leading to treatment withdrawal were reported. Clinically meaningful improvements were seen in EORTC QLQ-C30 items, including Global Health Status. Figure 1
Conclusion:
Alectinib (600mg twice daily) was well tolerated and demonstrated clinical efficacy in patients with ALK+ NSCLC disease who had progressed on prior crizotinib. A clinical benefit with alectinib was also observed in patients with CNS lesions at baseline. These data are preliminary; updated efficacy and safety data from a cut-off date of 27 April 2015 will be presented.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-063 - Dynamic Change of Fatigue for East-Asian Patients in the JMEN Trial (ID 843)
09:30 - 09:30 | Author(s): C.P. Belani
- Abstract
Background:
In the JMEN trial (Ciuleanu et al., Lancet 374:1432-1440, 2009), patients with advanced non-squamous non-small cell lung cancer (NSCLC) derived a benefit from pemetrexed maintenance therapy after platinum-based initial therapy by extending survival, delaying disease progression, and maintaining overall quality of life (QoL). However, fatigue was the most common physician-reported toxic effect in the pemetrexed treated group. We conducted a post-hoc analysis to investigate the dynamic change of fatigue in overall population and East-Asian (EA) patients treated on the JMEN trial.
Methods:
This analysis was performed in the overall safety population (N=656) and the EA subgroup safety population (N=152) mainly from China, Taiwan, and Korea including squamous and non-squamous NSCLC patients. The Common Terminology Criteria for Adverse Events (version 3.0) was used for summary of the AE incidence rates by cycle and AE severity reported by investigator. The Lung Cancer Symptom Scale (LCSS) was used to evaluate patients’ QoL. Worsening of fatigue was defined as an increase of 15 mm or more from baseline on a 100 mm scale in LCSS reported by the patients. The percentage of patients with worsening fatigue was also summarized by cycle. The time to worsening of fatigue symptom was analyzed using Kaplan-Meier method and Cox proportional model.
Results:
In the EA population drug-related fatigue (grade 1-4) occurred more frequently in pemetrexed arm compared with placebo arm (30.4% vs 16.0%, p=0.075). The grade 3/4 drug-related fatigue was rare in both arms (1 event reported in each arm). For both overall and EA populations, the fatigue incidence by cycle during the maintenance treatment with pemetrexed did not increase during subsequent cycles (Figure 1A, B). The percentage of patients who experienced worsening of fatigue based on the patients-reported LCSS scores was also comparable between the two arms in the overall and EA populations (Figure 1C, D). EA Patients in the pemetrexed arm experienced a numerically longer median time to worsening of fatigue compared to EA patients in the placebo arm, although the difference is not statistically significant (5.95 months vs. 3.91 months, HR= 0.84, 95% confidence interval [CI]: 0.51-1.37, p= 0.471). Figure 1
Conclusion:
These analyses suggest that despite a higher incidence of grade 1/2 drug-related fatigue compared with placebo, pemetrexed maintenance treatment for EA patients with advanced NSCLC will not impair patient-reported QoL.
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P2.01-068 - Androgen Deprivation Therapy for Prostate Cancer Associated with Improved Survival in Non Small Cell Lung Cancer: A SEER-MEDICARE Analysis (ID 2743)
09:30 - 09:30 | Author(s): C.P. Belani
- Abstract
Background:
Cancer of the prostate and lung are most commonly diagnosed in the elderly. Aberrant female sex hormone signaling has been well-described in NSCLC. The impact of androgen deprivation therapy (ADT) on non-small cell lung cancer (NSCLC) outcome has, however, not been well studied.
Methods:
We employed the linked SEER-MEDICARE database to assess the potential impact of ADT on NSCLC. We analyzed data from patients diagnosed with NSCLC between 1985 and 2005 and registered in the SEER-MEDICARE database. Patients were categorized into three groups: prostate cancer diagnosis followed by NSCLC (PL), NSCLC followed by prostate cancer (LP) and NSCLC only (L). Demographic and survival outcomes were compared between these groups. The impact of sequence of cancer diagnosis and ADT on survival post NSCLC diagnosis was assessed within the PL group using logistic regression model. Cox proportional hazards models were employed to estimate the effect of ADT and stage of prostate cancer on survival with adjustment for significant prognostic factors.
Results:
A total of 417630 patients were included in this analysis; male/female (56.4%/43.6%); Race: White (84.0%), Black (9.0%), Asian (2.1%), Hispanic (1.0%), others (3.0%); Stage: I (17.4%), II (2.9%), III (33.6%) and IV (46.1%). The majority of the patients were in the L group (96.3%), followed by PL (2.9%) and LP (0.8%). Patients in the LP group had the best 12-month survival rates (84.5%), followed by L (44.4%) and PL (40.1%). Analysis within the PL group showed an inverse correlation between stage of prostate cancer diagnosis and interval of time to NSCLC diagnosis: 54.8, 54.1, 62.1 and 59.3 months for stage I, II, III and IV prostate cancer, respectively. Prostate cancer patients exposed to ADT had a shorter interval to lung cancer diagnosis (48.3 vs. 52.7 months; p < 0.001). On multivariate analysis, patients exposed to ADT had a higher median survival (10 months vs. 9 months; p < 0.001) and reduced risk of death (HR:1.11; 95%CI:1.05-1.18), p <0.001).
Conclusion:
ADT therapy for prostate cancer was associated with improved survival for subsequent NSCLC diagnosis. Our result supports systematic exploration of ADT as a treatment strategy for NSCLC.
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P2.01-089 - A Phase 1b/2 Randomized Study of PEGPH20 in Combination with Docetaxel in Hyaluronan High NSCLC Patients Treated with Platinum Chemotherapy (ID 1705)
09:30 - 09:30 | Author(s): C.P. Belani
- Abstract
Background:
Patients with advanced non-small cell lung cancer (NSCLC) progressing after 1[st] line platinum containing doublet chemotherapy +/- targeted therapy for EGFR mutations and EML4-ALK fusion genes have limited therapeutic options. Extracellular components such as hyaluronan (HA) make up the tumor microenvironment (TME) and may limit access of chemotherapeutic agents to the cell as a result of increased interstitial pressure and decreased blood flow. PEGPH20 (PEG) decreases HA and restores blood flow. In animal models of NSCLC, PEG + docetaxel (Doc) significantly prolonged survival compared to Doc alone. These results are consistent with results in previous studies in pancreatic adenocarcinoma (PDA). In a Phase 1b trial of the combination of PEG + gemcitabine in Stage IV pts with PDA whose tumors were HA-high pts had higher ORR, PFS and OS compared to pts with HA-low tumors.
Methods:
This is an ongoing Phase 1b/2 open-label, randomized study of the addition of PEG to docetaxel (PDoc) compared to docetaxel (Doc) in pts with Stage IIIB/IV NSCLC having been treated with at least 1[st] line platinum containing chemotherapy. The Phase 1b portion of the study will determine the maximum tolerated dose (MTD), dose limiting toxicity and recommended Phase 2 dose for two schedules of PEG; one given every 21 days with Doc and the second dosed 2X per week with Doc. Up to 40 subjects are expected to be enrolled in the Phase 1b dose escalation. Once MTDs are determined the second portion of the Phase 1b will accrue approximately 10 patients whose tumors are HA-high to determine which schedule will go forward in Phase 2. The Phase 2 will randomize 188 patients in a 1:1 fashion to receive PDoc or Doc stratified by histology and prior targeted therapy. The primary endpoint of the Phase 2 portion is PFS. This is the first clinical trial evaluating PEGPH20 in NSCLC. The trial is currently accruing to the dose finding portion of the Phase 1b. ClinicalTrials.gov Identifier: NCT02346370
Results:
not applicable
Conclusion:
not applicable
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P2.01-096 - Randomized, Double-Blind, Placebo-Controlled Trial of Evofosfamide (TH-302) in Combination with Pemetrexed in Advanced ns-NSCLC (ID 659)
09:30 - 09:30 | Author(s): C.P. Belani
- Abstract
Background:
Tumor hypoxia is associated with chemo- and radioresistance and is a prevalent characteristic in tumors of patients with non-small cell lung cancer (NSCLC). Evofosfamide (previously known as TH-302) is a hypoxia-activated prodrug designed to release the bis-alkylating DNA crosslinker bromo-isophosphoramide mustard (Br-IPM) when reduced in severe hypoxia. In a Phase 1/2 study (NCT00743379) that included a single arm evofosfamide in combination with pemetrexed in 18 patients with relapsed/refractory non-squamous NSCLC, median PFS was 7.0 months and median OS was 14.9 months. Response in 15 evaluable patients: 6 partial responses (4 confirmed), 6 stable disease and 3 progressive disease. The most common adverse events were fatigue, anemia, stomatitis and nausea.
Methods:
An international, multicenter, randomized, double-blind, placebo-controlled trial was initiated to evaluate evofosfamide in combination with pemetrexed versus placebo and pemetrexed as a potential second-line treatment for patients with non-squamous NSCLC (NCT02093962). Approximately 440 patients will be enrolled with histologically confirmed stage IIIB or IV NSCLC with non-squamous histology, measurable disease according to RECIST 1.1, and ECOG performance status 0-1. Eligible patients have recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance. EGFR-activating and ALK rearrangements status must be known, and if identified, patients must have received a targeted kinase inhibitor. Evofosfamide (400 mg/m[2]) or matched placebo is administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m[2]) is administered by IV infusion 2 to 4 hours after evofosfamide administration on Day 1. Overall survival (OS) is the primary endpoint; secondary endpoints include safety, progression-free survival and RECIST response rate. The study design has 85% power to detect a 40% improvement in OS with a one-sided alpha of 0.025. The first patient was enrolled in June 2014; recruitment is ongoing.
Results:
not applicable
Conclusion:
not applicable
