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R. Feld
Moderator of
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MINI 17 - WT EGFR, Angiogenesis and OMD (ID 131)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 15
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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- Abstract
- Presentation
Background:
We have proposed that synergistic epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-chemotherapeutic interaction in lung cancer cells has 3 essentials: no platinum, cells not or no more sensitive to EGFR-TKI, and using a synergistic chemo partner, e.g., pemetrexed (P) (Tsai, et al. Lung Cancer 82:305, 2013).
Methods:
GENIUS study (NCT01579630) was a phase II, multicenter, randomized, open-label prospective trial comparing maintenance G/P versus P in patients with metastatic lung adenocarcinoma (mLADC) harboring no sensitizing EGFR mutations (sEGFRm) detected by high sensitivity methods following a 4-cycle P/Platinum induction therapy in frontline setting. Patients with no disease progression (PD) were 1:1 randomized to receive P (500 mg/m[2], 3-week cycle) ± G (250 mg, daily) until PD or treatment failure, and stratified by study site and response. The primary endpoint was progression free survival (PFS) by both independent radiologist review (IRR) and investigator assessment (IA), secondary endpoints included time to treatment failure (TTF), overall survival (OS), safety and toxicity profile.
Results:
Between 03/2011 and 11/2013, 55 patients were randomized, G/P 26, P 29. Baseline characteristics were balanced between arms (age 57; female 42%; never smoker 55%; ECOG1 91%; ≥2 metastatic sites 38.2%; ALK+ 16%). Median follow-up was 20.4 mo. Median cycle of treatment was G/P 9.5 (range 1-32) and P 4 (2-21). Median PFS was substantially longer for G/P than P, both by IRR (3 deemed as PD at randomization were excluded; n = 25 v 27): 8.4 v 3.8 mo; HR [95% CI] 0.42 [0.23-0.79]; p = 0.0057, and by IA: 8.7 v 2.9 mo; HR 0.38 [0.21-0.70], p = 0.0013. Response with induction therapy, age, and smoker had interactions with treatment for PFS. Median TTF: 7.0 v 2.9 mo; HR 0.46 [0.25-0.83], p = 0.0085. OS was also better for G/P than P by IRR (undefined v 29.3 mo; HR 0.44 [0.20-0.97]; p = 0.037) and IA (undefined v 21.7 mo; HR 0.46 [0.22-0.97]; p = 0.038). There were more treatment-related diarrhea, liver and skin toxicities on G/P v P, but generally mild. Two G/P patients were off-study due to liver toxicity.
Conclusion:
This proof of concept ph 2 study first demonstrated survival benefit of EGFR-TKI plus chemo in the maintenance phase of frontline treatment for patients with mLADC harboring no sEGFRm. This strategy deserves phase III study to confirm.
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MINI17.02 - SWOG 0709: Randomized Phase II Trial of Erlotinib vs. Erlotinib plus Carboplatin/Paclitaxel in Patients (Pts) with Advanced Non-Small Cell Lung Cancer (NSCLC) and Impaired Performance Status (PS2) as Selected by Serum Proteomics (ID 658)
16:55 - 17:00 | Author(s): P. Lara Jr., J. Moon, P.J. Hesketh, M. Redman, S. Williamson, F.R. Hirsch, P.C. Mack, D.R. Gandara
- Abstract
- Presentation
Background:
Advanced NSCLC pts with Zubrod PS2 are often excluded from clinical trials and platinum-based therapy. In SWOG 0341, erlotinib in PS 2 pts yielded progression-free (PFS) and overall survival (OS) of 2.1 and 5 months respectively. In a trial of erlotinib versus carboplatin/paclitaxel in PS2 pts (Lilenbaum, JCO 2008), PFS for erlotinib and chemotherapy were 1.9 and 3.5 months, respectively. Early reports suggested a potential role for serum proteomics in predicting erlotinib benefit beyond that of EGFR mutational status. We therefore conducted a prospective trial of erlotinib +/- chemotherapy in NSCLC pts with PS2 enriched by serum proteomics (Veristrat assay).
Methods:
Metastatic NSCLC pts with PS2, acceptable end-organ function, and “good” classification by serum proteomics were randomized to either Arm A (erlotinib 150 mg orally QD) or Arm B (erlotinib 150 mg orally QD on days 2-16 plus carboplatin AUC 5 IV day 1 and paclitaxel 200 mg/m2 IV day 1 x 4 cycles, followed by erlotinib 150 mg orally QD). Cycle length was 3 weeks. Arm B agents were “pharmacodynamically separated” to mitigate potential antagonism. The arm with superior observed median PFS would be selected for further evaluation, but only if ≥ 3 months. A sample size of 98 pts was based on a variety of assumed PFS probabilities for each arm. The trial was prematurely closed after the FDA determined midway through accrual that an IDE application was required for the proteomics assay; however SWOG had limited resources available for such filing.
Results:
Of 156 pts screened, 83 (59%) were classified as “good” by serum proteomics. 59 of 83 pts (60%) met trial eligibility and were randomized. Treatment-related grade 4 adverse events were seen in 2 pts in Arm A (thrombosis, hypomagnesemia) and 5 pts in Arm B (neutropenia -5, febrile neutropenia-1, leukopenia -1), with no treatment related deaths. Figure 1
Conclusion:
In Zubrod PS2 pts with advanced NSCLC and “good” classification by serum preoteomics, pharmacodynamically-separated erlotinib plus chemotherapy had better observed median PFS/OS versus erlotinib alone and surpassed the protocol-specified benchmark of PFS >= 3 months required for further study. Updated data will be presented.
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MINI17.03 - Prognostic and Predictive Value of the VeriStrat Classifier in Chemo-Naive NSCLC Patients Treated with Erlotinib or Placebo (TOPICAL Trial) (ID 699)
17:00 - 17:05 | Author(s): S. Lee, S. Nash, Y. Ngai, A. Hackshaw
- Abstract
- Presentation
Background:
National Comprehensive Cancer Network Guidelines recommend using VeriStrat, a blood proteomics test to determine using erlotinib instead of chemotherapy as second-line treatment for patients with non-small cell lung cancer (NSCLC). However, VeriStrat has not been evaluated in a first-line setting within a randomized trial.
Methods:
TOPICAL was a double-blind randomised placebo-controlled trial, for 670 chemotherapy-naive NSCLC patients (stage IIIb/IV) considered unsuitable for chemotherapy, mainly due to poor performance status (ECOG ≥2) or co-morbidities. They were randomized to receive best supportive care plus oral placebo or erlotinib (150mg/day) until disease progression/toxicity. Although there was no overall survival (OS) benefit among all patients, patients on erlotinib who developed first-cycle rash had improved OS, compared to placebo: hazard ratio (HR 0.76), p=0.006; unlike those without rash (HR 1.30, p=0.017). Pre-treatment serum samples were available for 477 of 670 (70%) TOPICAL patients. They were sent as anonymised aliquots to Biodesix for VeriStrat testing.
Results:
VeriStrat testing classified 52% (250/477) as having good outcomes, 46% (221) poor outcomes, and 6 unknown. In all patients, VeriStrat classification was associated with OS (good vs. poor: HR=0.58, 95%CI 0.47-0.73; P<0.0001) and PFS (HR=0.72; 95% CI 0.53-0.97; P=0.002), after allowing for gender, histology, stage, treatment and first-cycle rash (unadjusted HRs were similar, as were those ignoring rash). In all erlotinib patients, median OS was 4.9 (good) vs. 3.1 months (poor); HR=0.63, 95% CI 0.47-0.85, p=0.002. The corresponding results among all placebo patients were: 5.3 (good) vs. 2.9 months (poor), HR=0.53, 95% CI 0.39-0.73, p<0.001. Similar results were found for PFS: median 3.1 (good) vs. 2.2 (poor) months (HR=0.72; 95% CI 0.53-0.96, P=0.027) for erlotinib patients; and 2.8 vs. 2.4 months for placebo patients (HR=0.72, 95% CI 0.53-0.97, p=0.033). Among all patients, VeriStrat was not predictive: OS HR for erlotinib vs. placebo was 1.02 (95% CI 0.79-1.31) in the ‘good’ group, and 0.86 (95% CI 0.66-1.12) for ‘poor’; interaction p-value=0.38. Corresponding PFS HRs were 0.86 (95% CI 0.67-1.10) and 0.84 (95% CI 0.65-1.10); interaction p-value=0.92. VeriStrat was also not predictive when allowing for first-cycle rash (Table 1). However, among patients who had rash, those with ‘good’ classification had longer OS (p<0.001) and PFS (p=0.001) than those classified as ‘poor’. Figure 1
Conclusion:
Our large randomized trial among NSCLC patients considered unsuitable for chemotherapy shows that VeriStrat status was prognostic for OS and PFS; but it was not predictive for OS nor PFS, in relation to erlotinib vs. placebo as first-line treatment.
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MINI17.04 - Erlotinib in 2nd Line in Advanced Squamous NSCLC: Final Results of the Pepita Cohort (ID 822)
17:05 - 17:10 | Author(s): A. Vergnenegre, O. Molinier, I. Monnet, C. Audigier-Valette, N. Girard, P.J. Souquet, F. Blanchon, F. Bonnetain, H. Saal, J. Néaume, C. Lamour, M. Wislez
- Abstract
Background:
Erlotinib in 2[nd] line improves survival in patients with recurrent/progressive NSCLC, is also active in squamous cell NSCLC, as reported in a BR.21 study subgroup. So far, no prospective non interventional study has specifically evaluated patients with this histological subtype treated with erlotinib. We present the final results of PEPITA cohort.
Methods:
PEPITA is a French multicenter, prospective cohort study assessing erlotinib modalities of use in daily practice in squamous NSCLC. The primary endpoint was progression-free survival (PFS); secondary endpoints included patients’ characteristics, overall survival (OS), safety and quality of life. EGFR mutation was tested in 41 patients (28.5%) reason why exploratory analyses assessing EGFR genotyping and smoking status were also performed.
Results:
Between June 2012 - May 2013, 152 patients were included and 146 patients were analyzed for efficacy; median follow-up was 5.31 months (0.03-17.65).
* 2 patients without EGFR mutation status Efficacy and genotyping results were:Patients characteristics at baseline Efficacy population (n=146) EGFR tested (n=41) EGFR not tested* (n=103) p-value Mean age (±SD), years Men 67.7 (±8.6) 90.4% 67.4 (±8.9) 87.8% 67.8 (±8.6) 92.2% 0.79 0.52 ECOG PS 0/1 ECOG PS 2/3 17.5% / 43.8% 33.6% / 5.1% n=39 20.5% / 56.4% 23.1% / 0 n=96 16.7% / 38.5% 38.5% / 6.3% 0.09 Current smoker Former smoker Never smoker 28.8% 63.7% 7.5% 24.4% 63.4% 12.2% 31.1% 63.1% 5.8% 0.39 Comorbitities : Cardiovascular Endocrinological Pulmonary 63.0% 23.3% 19.9% 65.9% 22.0% 19.5% 62.1% 23.3% 20.4% 0.68 0.86 0.91
*[95% CI] In the safety population (n=152 patients), 158 adverse events (AEs) were reported in 70 patients (46.1%), including 48 grade ≥ 3 AEs in 31 patients (20.4%). The most frequent AEs related to erlotinib were skin rash (all grades [23,7%], grade ≥ 3 [5,2%]) and diarrhea (all grades [11,8%], grade ≥ 3 [2.0%]); 19 serious adverse events (SAEs) were reported in 12 patients (7.9%), including 16 grade ≥ 3 SAEs in 10 patients (6.6%). There were 6 SAEs leading to death (3.9% patients), but none SAE was related to erlotinib.EGFR mutation not tested n=103 EGFR mutation tested n=41 Non-smoker n=11 Smoker/Ex-smoker n=135 Efficacy population n=146 PFS Event (progression or death) 95 (92.2%) 34 (82.9%) 8 (72.7%) 123 (91.1%) 131 (89.7%) Median (months) 2.8 [2.3;3.2]* 4.4 [2.9;5.8]* 3.3 [0.7;ND]* 3.0 [2.7;3.5]* 3.0 [2.7;3.5]* Survival rates at 12 months 7.0% [3.1;13.1]* 10.7% [3.1;23.6]* 27.3% [6.5;53.9]* 6.3% [2.9;11.6]* 8.0% [4.2;13.4]* OS Event (progression or death) 79 (76.7%) 22 (53.7%) 6 (54.5%) 96 (71.1%) 102 (69.9%) Median (months) 5.5 [4.0;6.4]* 9.1 [4.4;ND]* 8.0 [1.6;ND]* 5.8 [4.5;7.1]* 5.8 [4.7;7.1]* Survival rates at 12 months 22.4% [14.5;31.3]* 37.1% [20.9;53.5]* 43.6% [14.7;69.9]* 24.8% [17.2;33.0]* 26.3% [18.9;34.3]*
Conclusion:
PEPITA is the first non-interventional study assessing modalities of use in daily practice of patients with stade IIIb/IV squamous NSCLC treated in 2[nd] line with erlotinib. This final analysis show similar efficacy and safety results to those observed in clinical trials. Clinical profile may drive EGFR genotyping.
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MINI17.05 - Discussant for MINI17.01, MINI17.02, MINI17.03, MINI17.04 (ID 3350)
17:10 - 17:20 | Author(s): R. Soo
- Abstract
- Presentation
Abstract not provided
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MINI17.06 - Subgroup Analysis of East Asian Patients in the Phase III REVEL Trial (ID 729)
17:20 - 17:25 | Author(s): J. Kang, K. Park, J. Kim, E.K. Cho, J. Shih, A.H. Zimmermann, P. Lee, E. Alexandris, T. Puri, M. Orlando
- Abstract
- Presentation
Background:
The REVEL trial demonstrated that second-line treatment with ramucirumab (RAM) plus docetaxel (DOC) significantly improved overall survival (OS) compared to placebo (PBO) plus DOC in the intent-to-treat (ITT) population (N=1253) of patients with stage IV non-small cell lung cancer. The REVEL trial also significantly improved progression-free survival (PFS) and objective response rates (ORRs). Results from the East Asia (EA) subgroup (Taiwan and Korea) analysis are presented.
Methods:
Subgroup analyses were performed in the EA ITT population, which consisted of all patients who were randomized in Taiwan (n=27) and Korea (n=62). Endpoints evaluated in the EA subgroup were OS, PFS, ORR, and safety. OS and PFS were analyzed using the Kaplan-Meier method and Cox proportional hazard model. Response was compared using the Cochran-Mantel-Haenszel test. ClinicalTrials.gov number NCT01168973.
Results:
In the 89 ITT EA patients, median OS was 15.44 months for the RAM plus DOC arm (n=43) and 10.17 months for PBO plus DOC arm (n=46) (HR: 0.762, 95% CI: 0.444–1.307). Median PFS was 4.88 months for the RAM plus DOC arm and 2.79 months for the PBO plus DOC arm (HR: 0.658, 95% CI: 0.408–1.060). The ORRs were 25.6% (95% CI: 13.5–41.2) in the RAM plus DOC arm and 9% (95% CI: 2.4–20.8) in the PBO plus DOC arm. Approximately two years after the enrollment of the first patient, in May 2012, the independent data monitoring committee recommended a reduction in the dose of DOC from 75 mg/m[2] to 60 mg/m[2] for newly enrolled EA patients, based on a higher incidence of neutropenia and febrile neutropenia associated with 75 mg/m[2] in EA patients compared to non-EA patients. This amendment resulted in a reduction in the toxicity associated with the original treatment regimen (Table). Table: Select grade ≥3 treatment-emergent adverse events, regardless of causality, by treatment arm and DOC dose in EA patients
Data are n (%). *Consolidated term.Preferred term RAM plus DOC (75 mg/m[2]) (n = 32) PBO plus DOC (75 mg/m[2]) (n = 33) RAM plus DOC (60 mg/m[2]) (n = 11) PBO plus DOC (60 mg/m[2]) (n = 13) Any 31 (96.9) 26 (78.8) 6 (54.5) 7 (53.8) Neutropenia* 26 (81.3) 24 (72.7) 6 (54.5) 5 (38.5) Febrile neutropenia 14 (43.8) 4 (12.1) 0 1 (7.7)
Conclusion:
Although not statistically powered to demonstrate significant improvement, the improved OS, PFS, and ORR observed in the EA subgroup treated with RAM plus DOC is consistent with the treatment effect observed in the overall ITT population in the REVEL trial. A dose reduction in DOC from 75 mg/m[2] to 60 mg/m[2] was associated with an improved safety profile and a reduction in the incidence of febrile neutropenia in the EA subgroup.
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MINI17.07 - Efficacy of Nintedanib/Docetaxel after Bevacizumab, Pemetrexed or Taxanes Therapy (ID 1521)
17:25 - 17:30 | Author(s): D. Heigener, M. Reck, A. Mellemgaard, S. Orlov, M. Krzakowski, J. Von Pawel, M. Gottfried, I. Bondarenko, S. Novello, J. Douillard, J. Barrueco, U. Von Wangenheim, R. Kaiser, J. Bennouna
- Abstract
- Presentation
Background:
Nintedanib is a triple angiokinase inhibitor of receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor and fibroblast growth factor. The randomized, placebo-controlled, Phase III LUME-Lung 1 study (NCT00805194; 1199.13) investigating nintedanib/docetaxel was the first trial of an antiangiogenic agent to demonstrate significant overall survival (OS) benefit in previously treated patients with non-small cell lung cancer (NSCLC) of adenocarcinoma histology; nintedanib/docetaxel is approved in the European Union for the treatment of patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after 1[st]-line chemotherapy. Here we report LUME-Lung 1 data from the adenocarcinoma population who received 1[st]-line chemotherapy containing bevacizumab, pemetrexed or taxanes.
Methods:
In LUME-Lung 1, 1314 patients with Stage IIIB/IV recurrent NSCLC received either nintedanib/docetaxel or placebo/docetaxel. Primary endpoint was centrally assessed progression-free survival (PFS); OS was a key secondary endpoint. Prior treatment with anti-VEGF agent bevacizumab was a stratification factor. Analyses of the adenocarcinoma population (n=658) according to prior treatment with bevacizumab (n=45 in either arm), pemetrexed (1[st]-line [n=126] or maintenance [n=27]) or taxanes (n=142) were performed to determine if 1[st]-line regimens could influence subsequent outcomes for nintedanib/docetaxel.
Results:
Patient characteristics were generally well-balanced across prior-treatment subgroups. For the adenocarcinoma population, there was no interaction between 1[st]-line treatment with bevacizumab, pemetrexed or taxanes and treatment outcome with nintedanib/docetaxel. Independent of pretreatment, nintedanib/docetaxel-treated adenocarcinoma patients had an OS benefit (Table). In the overall patient population, efficacy outcomes for these subgroups were also similar regardless of prior treatment. Furthermore, there was no significant effect on nintedanib/docetaxel outcomes for the few adenocarcinoma patients who received maintenance pemetrexed. The adverse event (AE) profile for nintedanib/docetaxel in each subgroup was consistent with that reported for the adenocarcinoma population in LUME-Lung 1, with diarrhea and reversible liver enzyme elevations among the more frequently reported AEs. Among patients who received nintedanib/docetaxel, there was no difference between prior-treatment subgroups in the frequency of AEs commonly associated with the prior treatment, such as hypertension with bevacizumab, mucositis with pemetrexed and peripheral neuropathy with taxanes.
Conclusion:
In LUME-Lung 1, regardless of whether a patient with NSCLC of adenocarcinoma histology received 1[st]-line chemotherapy containing bevacizumab, pemetrexed or taxanes, subsequent treatment with nintedanib/docetaxel led to improved OS.Table: OS results in patients with NSCLC of adenocarcinoma tumor histology stratified by ± prior 1st-line bevacizumab, pemetrexed or taxanes treatment
BEV, bevacizumab; CI, confidence interval; HR, hazard ratio; N/D, nintedanib/docetaxel; NSCLC, non-small cell lung cancer; OS, overall survival; PEM, pemetrexed; Pl/D, placebo/docetaxel; TAX, taxanes.No BEV BEV No PEM PEM No TAX TAX N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D Patients, n 298 315 24 21 261 271 61 65 245 271 77 65 Median OS, months 12.6 10.6 14.9 8.7 13.4 10.8 12.0 8.0 12.2 10.3 15.1 11.6 HR (95% CI) 0.85 (0.71–1.01) 0.61 (0.31–1.20) 0.83 (0.68–1.00) 0.79 (0.53–1.18) 0.86 (0.71–1.05) 0.75 (0.51–1.11) Interaction p-value p=0.24 p=0.90 p=0.61
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MINI17.08 - Tumor Growth Over Time with Nintedanib/Docetaxel or Placebo/Docetaxel in Adenocarcinoma NSCLC: Analysis From the LUME-Lung 1 Study (ID 1405)
16:45 - 16:50 | Author(s): M. Reck, H. Buchner, M. Gottfried, S. Novello, A. Mellemgaard, B. Gaschler-Markefski, R. Kaiser, J. Douillard
- Abstract
Background:
Nintedanib (N; Vargatef[®]), a triple angiokinase inhibitor, is approved in the EU in combination with docetaxel (D) for the treatment of patients with advanced NSCLC of adenocarcinoma histology (ACH) after 1[st]-line chemotherapy. In the randomized, placebo-controlled, Phase III LUME-Lung 1 study (NCT00805194; 1199.13), N+D significantly improved overall survival (OS; secondary endpoint) vs D in patients with ACH (median OS: 12.6 vs 10.3 months (m); HR: 0.83 [95% CI: 0.70–0.99]; p=0.0359) and in patients who progressed either during or within 9 m of 1[st]-line therapy (time[T]<9m) (median OS: 10.9 vs 7.9 m; HR: 0.75 [95% CI: 0.60–0.92]; p=0.0073). We explored the impact of on tumor growth over time as a treatment effect of N+D, with a specific focus on early progressors (T<9m) and patients who had progressive disease as best response to 1[st]-line therapy (PD-FLT).
Methods:
Tumor growth was evaluated using all available tumor measurements. Mixed-effects models were used to quantify the non-linear individual relationships between time from randomization and tumor burden, measured as the sum of longest diameter of target lesions (SLD) and assessed by independent central review (RECIST 1.0). Analyses were conducted for the entire population of patients with ACH, T<9m and PD-FLT.
Results:
Estimated mean baseline SLD was 82.5 mm in all patients with ACH, 88.3 mm in T<9m and 98.1 mm in PD-FLT. N+D showed a significant reduction of tumor growth over time (p<0.0001) in patients with ACH compared to D. Treatment difference at 6 months (SLD D group – SLD N+D group) for patients with ACH was 9.7 mm. This treatment difference was even more pronounced in the T<9m group (16.8 mm) and in patients with PD-FLT (19.7 mm). Tumor growth over time for N+D showed a non-linear J-shaped curve, indicating a decline in SLD at the beginning of treatment, which was maintained over time followed by a linear increase (see Figure for curves for the T<9m group). This relationship was consistently observed between populations. For patients treated with D, a linear increase in SLD from baseline over time in all ACH patients, T<9m and PD-FLT was observed. Figure 1
Conclusion:
In the LUME-Lung 1 study, N+D significantly decreased tumor burden and decelerated tumor growth over time compared to D in all patients with ACH and in the groups of patients with the poorest prognosis.
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MINI17.09 - Discussant for MINI17.06, MINI17.07, MINI17.08 (ID 3351)
17:30 - 17:40 | Author(s): T. John
- Abstract
- Presentation
Abstract not provided
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MINI17.10 - Oligometastatic Non-Small-Cell Lung Cancer and Unresectable Primary Tumor: Safety and Efficacy of Radical Treatment (ID 2669)
17:40 - 17:45 | Author(s): S. Marin, C. Salvador Coloma, J. Garde-Noguera, Ó. Juan Vidal, J. Garcia Sanchez, C. Escoin, J. Hidalgo, R.A. Albino, A. Llombart Cussac
- Abstract
- Presentation
Background:
Metastatic non-small cell lung cáncer (NSCLC) is associated with a poor prognosis, and palliative chemotherapy is the mainstay of treatment. However, long-time survival has been observed in oligometastatic patients treated with locally ablative therapies to all sites of tumoral disease. Oligometastatic NSCLC with unresectable primary tumor at diagnosis represents a therapeutic challenge, and nowadays there is limited evidence about the benefit of the treatment with radical intention of both primary tumor and metastases.
Methods:
Retrospective study of patients with oligometastatic (3 or less lesions, in a unique location) and unresectable NSCLC treated with radical chemo-radiotherapy at primary tumor and with surgery or stereotactic radiation therapy to the metastases. We have done a systematic review of clinical histories from NSCLC advanced patients diagnosed between October 2011 and March 2015. The aim of our study is to analyze the safety and efficacy of this treatment strategy in terms of response rate, progression free survival (PFS) and overall survival (OS).
Results:
Twenty-three patients met inclusion criteria. Median age 57 year, eighteen male (78,3%) and ECOG (0-1) 95,7%. Histology: 15 adenocarcinoma (65,2%), 5 squamous carcinoma (5%), and 3 (13%) others. All patients had unresectable mediastinal lymph nodes infiltration. Location of metastases included the brain (n=12, 52.2%), lung metastases (n=6, 26,1%), bone metastases (n= 3, 13%), adrenal (n=1, 4,3%) and lymph node (n=1, 4,3%). Chemotherapy: 9 CDDP-Pemetrexed (39,1%), 9 CDDP-Vinorelbina (39,1%), 3 Carboplatin-paclitaxel, 1 CDDP-Gemcitabina (4.3%), 1 CDDP-Docetaxel (4.3%). Ten patients (43.5%) received sequential thoracic radiotherapy and 12 (52.2%) concomitant. Metastases treatment: 12 stererotactic radiation (52.2%), 7 external radiotherapy (30, 4%), 3 surgery (13%), 1 radiofrequency (4.3%). Toxicity: four patients (17,39%) developed G3 toxicity (2 hematological, 1 pneumonitis, 1 esophagitis). Median follow up was 15 months, median OS 18 m, median PFS 11 months. The 1-year OS were 73.9%, 2-year OS 21,7% and 3-year OS 8.7%.
Conclusion:
Radical treatment of oligometastatic and unresectable NSCLC patients is a safe therapeutic strategy. Despite the limited data and the small numbers of our study, it could be contemplated as an effective therapeutic alternative for selected patients.
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MINI17.11 - Results of Radical Local Treatment of Non-Small Cell Lung Cancer Patients with One or Two Synchronous Metastases (ID 581)
17:45 - 17:50 | Author(s): M. Kwint, H. Peulen, S. Burgers, K. Hartemink, M. Verheij, J. Belderbos
- Abstract
- Presentation
Background:
Stage IV non-small cell lung cancer (NSCLC) patients are considered incurable and mainly treated with palliative intent. The overall survival (OS) and disease free survival (DFS) of this patient group is considered as poor. The purpose of this study was to investigate the OS and DFS of NSCLC patients, diagnosed with synchronous oligometastatic disease treated with curative intent of the intrathoracic disease as well as the metastases.
Methods:
Patients treated between 2008 and 2014 were included in this retrospective cohort analysis. Main inclusion criteria were: synchronous presentation of NSCLC and oligometastatic disease at diagnosis, and multidisciplinary consent on a radical treatment of both the intrathoracic disease and the metastases. Besides systemic treatment. The intrathoracic disease was radically irradiated (> 55 Gy biological effective dose) or resected. Treatment of the metastases consisted of: radical/stereotactic radiotherapy, surgical resection or radiofrequency ablation (RFA).
Results:
A total of 56 patients, 31 men and 25 women, were included. The mean age was 61 years (range 36-79) and all were in good condition (WHO 0-1). Most patients had a solitary metastasis (brain (22), bone (17), adrenal gland (6), lymphe node (3), liver (2), soft tissue (1), pulmonary (1), thyroid gland (1) and breast (1)). Two patients had 2 metastases (liver and bone / pleural and bone). The intrathoracic tumor stage,ignoring M-status, was IA in 3 patients, IB in 2 patients, IIA in 8 patients, IIB in 4 patients, IIIA in 24 patients and IIIB in 15 patients. Fifty patients were treated with radiotherapy and 4 patients had a surgical intervention for the primary tumor; 2 patients only received systemical treatment for the intrathoracic disease. Fifty patients received chemotherapy (89%), of which 5 (10%) concurrent with the radiotherapy of the intrathoracic disease and 45 (90%) sequential. The metastases were treated with ablative/stereotactic radiotherapy (45), surgical intervention (2), only systemical treatment (5), combination of surgical intervention and radiotherapy (3) and RFA (1). The mean follow-up was 21 months (range 4-69). Forty-one (73%) patients developed recurrent disease of whom 29 (52%) died. Only 8 (20%) recurrences occurred within the irradiated area. Most recurrences where brain (13) and pulmonary metastases (11). For the whole group, the median DFS was 14 months (range 2-69, 95% CI 11-17) and the median OS was 32 months (range 4-69, 95% CI 16-48). The 1- and 2-year OS was 86% and 58%, respectively. The 1- and 2-year DFS was 66% and 30%, respectively.
Conclusion:
Radical local treatment of a highly selected group of NSCLC patients in good condition presenting with synchronous oligometastatic stage IV disease (maximum 2 metastases) resulted in excellent local control, and also in favorable long-term DFS and OS.
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MINI17.12 - Survival Analysis of Stage IV NSCLC with Synchronous Isolated Metastasis in a Large Retrospective Cohort (ID 752)
17:50 - 17:55 | Author(s): M. Duruisseaux, M. Perrin, M. Giaj Levra, L. Sakhri, P. Brichon, J. Villa, D. Hoffmann, P. Guillem, D. Moro-Sibilot, A.C. Toffart
- Abstract
- Presentation
Background:
Stage IV Non-Small Cell Lung Cancer (NSCLC) is considered as an incurable disease with median survival of 6 to 12 months. Palliative platinum based chemotherapy is the standard therapy. It has been suggested that patients with one synchronous isolated metastasis (SIM) suitable for local therapy have longer survival.
Methods:
Database of the Multidisciplinary Thoracic Oncology Group of our centre was retrospectively screened from 1993 to 2012. Consecutive NSCLC of any stage were included. Median overall survivals (OS) between stage III and stage IV (SIM and non SIM) were compared with log-rank test. For the multivariate analyses Cox models were performed.
Results:
4917 patients were registered, 85 were excluded because of missing data. Among the study population, 1335 (27.6%) patients were stage III NSCLC, 1483 (31%) non SIM stage IV and 109 (2%) SIM stage IV. SIM site were mainly brain (n=70, 64%) and adrenal gland (n=16, 15%). Clinical and histological data differed substantially between each stage (Table 1). Median OS was significantly longer in SIM stage IV compared to non-SIM stage IV (18 [IQR, 9-33] months vs 6 [IQR, 2-13] months respectively, p-value<10[-4]) and not significantly different between SIM stage IV and stage III (14 months [IQR, 6-31], p-value=0.05). In multivariate analysis (Table 2), we still observed that median survival of SIM stage IV and stage III were not significantly different (p-value= 0.47).Figure 1 Figure 2
Conclusion:
OS of SIM stage IV is remarkably improved compared to non SIM stage IV, and comparable to stage III. This data supports aggressive treatment in the subgroup of SIM stage IV.
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MINI17.13 - Prognosis of Stage III NSCLC Patients Presenting with Isolated Brain Failure after Definitive Concurrent Chemoradiotherapy (ID 1338)
17:55 - 18:00 | Author(s): E. Topkan, B. Akkus Yildirim, O.C. Guler, Y. Ozdemir
- Abstract
Background:
We retrospectively investigated the survival outcomes of stage III non-small-cell lung cancer (NSCLC) patients presenting with isolated brain failures (IBF) after definitive concurrent chemoradiotherapy (C-CRT) and treated with whole brain radiotherapy (WBRT) ± stereotactic radiosurgery (SRS) or surgery.
Methods:
A total of 162 patients with stage III NSCLC who were treated with platinum based C-CRT between January 2007 and December 2012 and presented with proven IBF with/without locoregional failures were included in this retrospective analysis. All patients received WBRT of 20-30 Gy (3-4 Gy/fx) ± SRS of 16-22 Gy or surgery. The primary and secondary end points were overall survival (OS) and identification of factors associated with longer survival.
Results:
Median follow-up was 12.7 months from the IBF diagnosis.IBF occurred at median 7.8 months (range: 1.7-46.4) from the commencement of C-CRT.WBRT was the sole local intervention in 78 patients whereas 55 and 29 patients received additional SRS or surgery mostly prior to WBRT. Median and 3-year survival rates were 11.7 months and 20.4%, respectively. In univariate analysis, controlled primary (20.3 vs. 6.4 months; p<0.001) and absence of extracranial metastasis development during follow-up (23.3 vs. 10.6 months; p<0.001) were determined to be significantly associated with longer OS times, which also retained their independent significance in multivariate analysis. Addition of SRS or surgery was related with better brain control rates but not OS in overall population. However, in patients presenting with ≤3 brain lesions and controlled lung primary the addition of SRS or surgery to WBRT was associated with significantly superior OS times than WBRT alone (25.8 vs. 8.2 months; p<0.001).
Conclusion:
Present results demonstrated that controlled lung primary and absence of extracranial metastasis development during follow-up period were the factors positively associated with longer OS after WBRT ± SRS or surgery in stage III NSCLC patients presenting with IBF after platinum based C-CRT.Additionally, our results suggested superior survival with addition of SRS or surgery to WBRT in patients with 1-3 brain lesions and controlled lung primaries.
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- Abstract
Background:
The effectiveness of pulmonary metastasectomy for non-small cell lung cancer(NSCLC) is controversial. The aim of this study is to report the overall survival after pulmonary metastasectomy for NSCLC and to determine prognostic factors for survival.
Methods:
Between June 2003 and July 2007, 39 patients underwent pulmonary metastasectomy in single center. Data from first time of pulmonary metastasectomy were included and data from more than second time of pulmonary metastasectomy were excluded.
Results:
There were 24 men and 15 women, and the median age at pulmonary metastasectomy was 64.0 years. The median recurrence free time from initial pulmonary resection to pulmonary metastasectomy was 18.5 months. The overall 5-year survival rate was 67.2%. In univariate analysis, ager under 70 years, recurrence free time over 24 months, adenocarcinoma and normal CEA level were prognostic factors for overall survival. Gender, initial TNM stage, operation type of pulmonary metastasectomy, number and size of pulmonary nodule and distance from nodule to margin were not associated with overall survival.
Conclusion:
In selected patients, pulmonary metastasectomy for NSCLC may confer a good survival. It appears reasonable that such patients should be considered as surgical candidates.
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MINI17.15 - Discussant for MINI17.10, MINI17.11, MINI17.12, MINI17.13, MINI17.14 (ID 3352)
18:05 - 18:15 | Author(s): M.L. Johnson
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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MINI05.13 - Treatment of EGFR/ALK-Driven Non-Small Cell Lung Cancer (NSCLC) Brain Metastases: Impact of First-Line Whole Brain Radiotherapy on Outcome (ID 1251)
17:55 - 18:00 | Author(s): R. Feld
- Abstract
- Presentation
Background:
Brain metastases (mets) in EGFR/ALK-driven NSCLC are common, and frequently pose treatment dilemmas. Effective systemic therapy with tyrosine kinase inhibitors (TKIs) controls extracranial disease in up to 70% of patients, but often radiotherapy is required for intracranial control. As whole brain radiation (WBRT) may be associated with neurocognitive toxicity, we aimed to evaluate the impact of molecularly targeted therapy and stereotactic radiotherapy (SRS) for EGFR/ALK-driven NSCLC on intracranial disease control with and without WBRT.
Methods:
This retrospective analysis included patients treated with EGFR/ALK-positive NSCLC at Princess Margaret Cancer Centre from 1998-2015, with brain mets at lung cancer diagnosis or during treatment/follow-up. Demographic data were collected from electronic patient records. Time to intracranial progression (TTIP) and overall survival (OS) were calculated from date of diagnosis of brain mets, using the cumulative incidence function and Kaplan-Meier methods respectively; differences between groups were tested with Gray’s or log-rank test.
Results:
From 1998-2015, 162 patients with brain mets from EGFR/ALK-driven NSCLC were identified: 138 in the EGFR cohort, 23 in the ALK cohort and one included in both cohorts for analysis, whose tumour carries both an EGFR mutation and ALK rearrangement. Table 1 contains clinical characteristics and treatment details. In the EGFR cohort, initial brain mets treatment consisted of systemic therapy alone in 19 patients (17 TKI, 2 chemotherapy), SRS +/- surgery in 27 patients and WBRT +/- SRS/surgery in 88 patients. 1-year intracranial progression rates were 26%, 32% and 12%, respectively, and median TTIP was 18, 16 and 40 months [p=0.12]. Median OS was 26, 27 and 34 months respectively [p=0.49]. In the ALK cohort, initial brain mets treatment consisted of systemic therapy alone in 4 patients (1 TKI, 3 chemotherapy), SRS/surgery alone for 4 patients and WBRT +/- SRS/surgery for 15 patients. 1-year intracranial progression rates were 50%, 50% and 13%, respectively, and median TTIP was 18, 14 and 69 months [p=0.028]. Median OS was 35 months, not reached and 51 months, respectively [p=0.75]. Multivariable analysis for the whole group showed that age [p=0.021], number of brain mets [p=0.012] and extracranial control [p=0.008] were significantly associated with OS, but not WBRT [p=0.61].
Conclusion:
In this cohort of patients with brain mets from EGFR/ALK-driven NSCLC, patients treated with WBRT trended to longer TTIP. Although not statistically significant, our data also show a trend towards longer survival in patients who received WBRT. These observations require further validation in this patient population.EGFR (N=139) ALK (N=24) Median Age (Range) 59(29-86) 53(31-77) Female Sex 93(67%) 15(62%) Ethnicity Asian Caucasian Other 58(42%) 63(45%) 18(13%) 7(29%) 13(54%) 4(17%) Smoking Never Smoker Former/Current Smoker Unknown 108(77%) 30(22%) 1(1%) 19(79%) 5(21%) 0 ECOG PS (Diagnosis) 0 1 2-4 66(48%) 67(48%) 6(4%) 7(29%) 14(58%) 3(13%) Brain Mets at Stage IV diagnosis 93(67%) 13(52%) Number of Brain Mets 1 2-4 5+ N/A 32(23%) 39(28%) 62(45%) 6(4%) 9(38%) 6(24%) 9(38%) 0 Symptomatic Brain Mets No Yes 78(56%) 61(44%) 16(67%) 8(33%) Initial Brain Mets treatment WBRT WBRT+SRS/Surgery SRS+/-Surgery Systemic Therapy None 71(51%) 17(12%) 27(19%) 19(14%) 5(4%) 13(54%) 3(12%) 4(17%) 4(17%) 0
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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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MINI29.12 - Patients with Advanced Non-Small Cell Lung Cancer: Are Research Biopsies a Barrier to Participation in Clinical Trials? (ID 663)
19:35 - 19:40 | Author(s): R. Feld
- Abstract
- Presentation
Background:
The evolution of targeted therapy in non-small cell lung cancer (NSCLC) has led to growing complexity of clinical research and a heightened expectation of clinical benefit for participants. Clinical trials in NSCLC increasingly require mandatory tumour samples or research biopsies, both potential barriers for trial participation. We assessed the impact of performing research biopsies in advanced NSCLC on clinical trial enrollment.
Methods:
We conducted a retrospective chart review of patients with advanced NSCLC evaluated for systemic therapy clinical trials at the Princess Margaret Cancer Center from January 2007 to March 2015.
Results:
Of 55 clinical trials reviewed, 38 required tumor samples for enrolment. Six mandated fresh tumor biopsies, whereas archival samples were permitted for 32 trials. All studies were linked to investigational therapy except one trial of molecular profiling not linked to an investigational treatment. Confirmation of a pre-specified biomarker was required in 23 trials in order to receive investigational treatment. Trial participation was offered to 640 patients at 940 unique study encounters, with some patients enrolling in multiple trials. Of 549 encounters where study treatment was offered, 60% proceeded to receive study treatment. Those considering trials without mandatory tissue requirements were more likely to proceed to study enrolment than those considering trials with these requirements (83% vs. 55%, p<0.0001). Those considering trials permitting use of archival tissue were more likely to begin study treatment than those considering trials mandating fresh research biopsies (59% vs. 38%, p=0.0007). For trials requiring current tumour samples, 127 research biopsies were performed. Participants proceeded to study treatment in 51% of these encounters. Study treatment was not offered for the remaining encounters due to lack of the pre-specified biomarker (28%), insufficient biopsy tissue (6%) or non-biopsy related exclusion criteria (15%). Among all 549 trial encounters, the most common barriers to trial enrollment included lack of the pre-specified biomarker (35%), withdrawal of consent (20%), other study exclusion criteria (16%), insufficient biopsy tissue (10%), deteriorating clinical status (10%) and death (5%). Of 391 encounters for the molecular profiling trial, 72% successfully completed molecular profiling. Twenty-two percent had insufficient tissue for analysis and 3% died prior to completion of molecular profiling.
Conclusion:
With the evolution of personalized medicine, a growing number of NSCLC trials require tumour tissue for treatment eligibility. This has emerged as a significant barrier to clinical trial enrollment. Potential solutions include routine tissue banking at diagnosis, facilitating use of available diagnostic samples (e.g. fine needle aspirates) for trials, development of circulating DNA assays for trials, and more resources for timely tissue acquisition.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-044 - EGFR and ALK Status Influence Health Utility and Global Quality of Life Scores in Patients with Metastatic Lung Cancer (ID 1613)
09:30 - 09:30 | Author(s): R. Feld
- Abstract
Background:
EGFR mutations and EML4-ALK rearrangements play important roles in prognosis and response to treatment. While extending survival is a main goal of treatment, improving symptoms, well-being, and quality of life is an equally important priority.
Methods:
At Princess Margaret Cancer Centre, a cross-sectional study evaluated 224 outpatients with metastatic lung cancer who completed demographic and EQ5D-3L questionnaires generating health utility scores (HUS, 0-1) and a visual analogue scale (VAS) slider (0-100). Patients rated their ECOG performance status (0-4), and described their health over the last month from 1 (excellent) to 5 (poor). Results were correlated with clinical and demographic data. Our objective was to compare HUS and global quality of life by mutational status. Patients with EGFR mutations and ALK rearrangements were enriched through targeted enrolment, while patients with neither alteration were selected randomly from the same outpatient clinics.
Results:
94 patients (42%) had an EGFR mutation, 23 (10%) an ALK rearrangement and 107 (48%) had neither (“wildtype”) in their tumor. Participation rate was 87%. Characteristics of the populations were as expected, with higher rates of never smokers in patients with EGFR or ALK alterations (p<0.0001), greater proportion of Asians (p=0.0004), and higher proportion of adenocarcinoma (p<0.0001). Current systemic treatment differed among groups, as the majority of patients with driver mutations were receiving targeted agents at the time of assessment (77% EGFR and 65% ALK vs 7% wildtype). Conversely, wildtype patients were more likely on chemotherapy (6% vs 17% vs 38%) or not on treatment (17% vs 17% vs 47%, p<0.0001). Patients filled questionnaires on average 25 months after initial diagnosis of lung cancer. Patients with EGFR mutations (97%) or ALK rearrangements (100%) were more often ECOG performance status 0-1 at the time of diagnosis of stage IV disease than wildtype individuals (86%, p=0.02). For quality of life analysis, we regrouped the patients with EGFR/ALK alterations (n=117). Their mean HUS was better than for wildtype patients (0.80 vs 0.71, p=0.0003), their mean VAS slider was higher (66.9 vs 60.8, p=0.0381) and their mean self-rated ECOG scores was better (0.90 vs 1.26, p=0.022).
Conclusion:
In a clinical population, patients with metastatic lung cancer harboring EGFR and ALK alterations report superior HUS and global quality of life scores when compared with patients without these molecular changes, during the course of their therapy. This is reflected in higher proportion of patients on active therapy, particularly with molecularly targeted agents, and with improved self-reported performance scores. Health utility values used in economic analyses of metastatic lung cancer patients in clinical practice should be specific for different mutations.
