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M. Ahn
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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: 2
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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MINI05.04 - Survival Outcome Assessed According to Tumor Burden & Progression Patterns in Patients with EGFR Mutant NSCLC Undergoing EGFR-TKIs (ID 886)
17:00 - 17:05 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Mutations in the epidermal growth factor receptor (EGFR) are associated with a marked therapeutic response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). However, clinical predictors of the survival benefit of EGFR-TKI treatment in NSCLC with EGFR activating mutations have not been well elucidated. Therefore, this study evaluated clinical predictors of survival outcome in patients with EGFR mutant NSCLC who were treated with EGFR-TKIs. Mutations in the epidermal growth factor receptor (EGFR) are associated with a marked therapeutic response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). However, clinical predictors of the survival benefit of EGFR-TKI treatment in NSCLC with EGFR activating mutations have not been well elucidated. Therefore, this study evaluated clinical predictors of survival outcome in patients with EGFR mutant NSCLC who were treated with EGFR-TKIs.
Methods:
A total of 224 patients with EGFR-mutant lung adenocarcinomas that were treated with EGFR-TKIs were retrospectively reviewed. Treatment outcomes were evaluated based on clinical factors, number of metastasis site and progression patterns.
Results:
The clinical factors associated with reduced progression-free survival (PFS) and overall survival (OS) by univariate analysis were ECOG performance status (PS) ≥ 2, intra- and extrathoracic metastasis, presence of extrathoracic metastasis, high number of metastasis sites, metastasis to liver or adrenal gland at baseline, and rapid progression of primary tumor at the time of progressive disease (PD). In multivariate analysis, factors that remained significantly associated with shorter PFS were ECOG PS ≥ 2 (Odds ratio [OR] 2.189 [95% CI, 1.374 – 3.437]; P < 0.001) and rapid progression of primary tumor at PD (OR 1.800 [95% CI, 1.059 – 3.058]; P = 0.030).
Conclusion:
Thus, tumor burden, expressed as the number of metastasis sites at the time of EGFR-TKI treatment, and rapid progression of primary tumor at PD are predictive of inferior survival in patients with lung adenocarcinoma with activating EGFR mutations.
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MINI05.06 - A Phase Ib/II Study of Afainib plus Nimotuzumab in Non-Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib (ID 667)
17:15 - 17:20 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Afatinib (A) is a potent irreversible EGFR TKI and nimotuzumab (N) is a humanized anti-EGFR mAb. In this phase Ib/II study, we aimed to assess the safety and activity of A plus N in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib.
Methods:
Major inclusion criteria were advanced NSCLC with activating EGFR mutation or disease control for at least six months with previous gefitinib or erlotinib therapy. In the phase Ib study using classic 3+3 dose escalation method, patients were treated with A 40mg/d or 30mg/d in combination with N 100mg/w or 200mg/w. One cycle was composed of 4 weeks of treatment. In the phase II study, patients were treated with A plus N in the level of RP2D defined in the phase Ib study.
Results:
Overall, fifty pts were enrolled and treated: 13 in phase Ib and 37 in phase II. At the starting dose level (A 40mg/d + N 100mg/w), one out of 6 pts experienced end-of-cycle 1 DLT (G3 diarrhea), and the dose was up to the next level of A 40mg/d + N 200mg/w. Out of 6 pts at this level, 2 pts experienced DLTs (G3 diarrhea and G3 neutropenia, respectively), and RP2D was accordingly determined as A 40mg/d + N 100mg/w. In the whole treatment duration of the phase II, there was no treatment related death and 10 pts (20%) experienced any grade 3 adverse event, including diarrhea and skin rash. Out of evaluable 50 pts in the phase Ib/II study, the response rate was 36% (18 achieved partial response out of 50) and the median PFS was 4.4 months (95% CI:3.2-5.5 months).
Conclusion:
A and N showed an acceptable safety profile and promising antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib.
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.06 - AZD9291 in Pre-Treated T790M Positive Advanced NSCLC: AURA Study Phase II Extension Cohort (ID 943)
17:15 - 17:20 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
AZD9291 is an oral, potent, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), selective for both EGFR-TKI-sensitizing (EGFRm) and T790M resistance mutations. The Phase I AURA study was a dose escalation/expansion study in patients with EGFRm positive advanced non-small cell lung cancer (NSCLC) who had progressed after EGFR‑TKI treatment. The 80 mg once daily (qd) dose was chosen for further evaluation in a Phase II extension cohort of the AURA study, and in an additional Phase II study (AURA2). Here we report efficacy and safety of AZD9291 from the AURA study Phase II extension cohort (NCT01802632) in patients pre-treated with EGFR-TKI and with centrally confirmed T790M positive advanced NSCLC.
Methods:
Eligible patients had measurable disease, World Health Organization performance status (WHO PS) 0 or 1, and acceptable organ function; stable brain metastases were allowed. A mandatory tumor sample was taken after disease progression on the most recent line of therapy, for prospective confirmation of T790M positive status by central laboratory testing (cobas™ EGFR Mutation Test). Patients received AZD9291 at 80 mg qd until disease progression. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 (assessed by independent central review, ICR). Secondary objectives included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), investigator-assessed ORR, and safety. Planned enrollment was 175 patients to give an estimate of the ORR with 95% CI within ±8%. Data cut-off was January 9, 2015 after all patients should have undergone the second tumor assessment.
Results:
201 patients were dosed in the extension cohort of the study; two patients without measurable disease at baseline by ICR were excluded from the evaluable-for-response set. By central testing, EGFR mutation subtypes were: T790M, 98%; Ex19del, 71%; L858R, 25%; other, 3%. Median age was 62 years; female, 66%; Asian, 57%; WHO PS 0/1/2, 34%/66%/1%; second/≥third-line, 30%/70%. At the data cut-off, median treatment exposure was 4.9 months and 168 patients remain on treatment. ORR by ICR was 58% (115/199; 95% CI 51, 65) and DCR was 92% (95% CI 87, 95). ORRs were similar across lines of therapy (second-line, 59.0% [36/61] vs ≥third-line, 57.2% [79/138]). Investigator-assessed ORR was 68% (137/201; 95% CI 61, 75). Median DoR and median PFS have not been reached (maturity 2% and 21%, respectively). The most common all-causality adverse events (AEs) were diarrhea, 41% (0.5% Gr≥3) and grouped rash terms 37% (0.5% Gr≥3); 42 (21%) patients experienced Gr≥3 AEs. Interstitial lung disease grouped terms were reported in five (2.5%) patients, one of which was fatal (0.5%) and considered possibly causally related to AZD9291 by the investigator. Eight patients (4%) discontinued treatment due to an AE. Updated results from a later data cut-off will be available for presentation.
Conclusion:
In the AURA study Phase II extension cohort, AZD9291 80 mg qd demonstrates clinical activity, manageable tolerability, and a low discontinuation rate in patients with centrally confirmed EGFR T790M positive advanced NSCLC that has progressed on or after EGFR‑TKI treatment. These data provide further validation of the results from the Phase I study cohorts.
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MINI16.09 - Design, Execution, and Preliminary Biomarker Results from Paired Tumor Biopsy Cohorts of the AZD9291 AURA Trial (ID 941)
17:30 - 17:35 | Author(s): M. Ahn
- Abstract
Background:
Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) exhibits sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib; however, acquired resistance eventually develops in most patients. The most common mechanism of TKI resistance is a second-site mutation in the EGFR kinase domain, T790M. AZD9291 is an oral, potent, irreversible EGFR-TKI with potency against both T790M resistance and sensitizing EGFR mutations. In the ongoing Phase I AURA study (NCT01802632), AZD9291 induced durable responses in patients with acquired resistance to EGFR-TKIs. We report results of paired biopsy cohorts of the AURA trial, reviewing modulation of key molecular biomarkers of AZD9291 activity in patient tumor samples.
Methods:
Two cohorts of patients on the AURA trial were consented for collection of paired tumor biopsies. These patients had a pre-study tumor biopsy with T790M positive tumor status confirmed by central laboratory EGFR testing (Cobas™ EGFR Mutation Test). Following 8 to 15 days of once daily AZD9291 treatment (80 or 160 mg), a post-dose tumor biopsy was obtained. Baseline and post-dose tumor tissue was processed for routine histology and pathologic evaluation. More than 100 viable tumor cells per sample were required for subsequent biomarker scoring. Formalin-fixed paraffin-embedded tumor biopsies were profiled by immunohistochemistry with a suite of key pathway and tumor-relevant markers (phospho[p]-EGFR, pERK, pAKT, pS6, PD-L1, CD8). Matching plasma pharmacokinetic samples were also obtained for PK-PD correlations.
Results:
As of February 2015, 58 potential patients with an evaluable baseline biopsy were identified as candidates for post-dose biopsy collection. Sixteen of these patients did not proceed to an on-study biopsy as the identified lesions had regressed too substantially or were no longer considered suitable for re-biopsy, one patient was medically excluded from re-biopsy, and one patient’s sample was not available. In total, 40 patients supplied matched pre- and on-treatment biopsies. As of March 2015, paired tumor samples were available for QC from 26 of these 40 patients. Ten of these 26 biopsy specimens subsequently failed QC due to inadequate tumor content, leaving 16 paired tumor samples available for biomarker analyses, of which five have thus far been evaluated. AZD9291 treatment resulted in the inhibition of EGFR pathway components in the majority of post-treatment tumor biopsies. Tissue biomarker analyses are ongoing and updated data on evaluable biopsy pairs will be reported at the time of the congress.
Conclusion:
The completion of a paired biopsy cohort within the AURA trial was challenging due to the rapid onset of anti-tumor effects of AZD9291. Approximately 29% (17/58) of potentially eligible patients were unsuitable for the post-dose biopsy procedure due to tumor regression and 38% (10/26) of available post-dose biopsies were found to contain too little tumor for analysis. In the evaluable tumor pairs, pharmacodynamic modulation of the EGFR pathway was evident. Further biomarker analyses, including evidence of modulation of immune system markers, may help inform future combination strategies.
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MINI 26 - Circulating Tumor Markers (ID 148)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:M. Macmanus, C. Aggarwal
- Coordinates: 9/09/2015, 16:45 - 18:15, 205+207
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MINI26.11 - Longitudinal Monitoring of EGFR Mutations in Plasma of EGFR Mutant NSCLC Patients Treated with EGFR TKIs: Korean Lung Cancer Consortium (ID 1130)
17:40 - 17:45 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Detection of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) patients is mainly based on tissue biopsy, which is invasive and time consuming. Furthermore, there is still a need for serial monitoring of EGFR mutations and detection of EGFR tyrosine kinase inhibitors (TKIs) resistance. We hypothesized that plasma-based EGFR mutation analysis may be feasible for monitoring response to EGFR TKIs and could be used to predict the resistance.
Methods:
From January 2012 to October 2014, 200 EGFR mutant NSCLC patients were enrolled and treated with EGFR TKIs (141 patients for gefitinib, 46 patients for erlotinib, and 13 patients for afatinib). Plasma samples were prospectively obtained every 2 months from baseline until disease progression. The longitudinally collected plasma samples (n = 368) from 81 patients who progressed were analyzed using droplet digital PCR (ddPCR). We identified an association between serial EGFR mutant titers in plasma cell-free DNA (cfDNA) samples and the patient’s clinical response to EGFR TKIs.
Results:
Of a total 58 baseline cfDNA samples available for ddPCR, 43 (74%) samples demonstrated same mutation in the matched tumors (i.e. sensitivity: 70.8% (17/24) for L858R vs 76.5% (26/34) for exon 19 deletions). The concordance rate of plasma with tissue results of EGFR mutation was 88% for L858R and 86% for exon 19 deletion, respectively. Of the 54 patients with both before and after treatment plasma samples, 40 patients showed a dramatic decrease of mutant copies (greater than 50%) in blood in the first 2 months after treatment. We also found the secondary mutation (T790M) emerged in 28 patients around 3~13 months after treatment and in 4 patients before the treatment. Elevated circulating mutations (L858R/ex19/T790M) can be detected in 5 patients before disease progression as determined by CT scan.
Conclusion:
These results suggest that ddPCR is an appropriate method for determining plasma-based EGFR mutation status and may aid in monitoring response to EGFR TKIs and early detection of EGFR TKIs resistance.
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MINI 30 - New Kinase Targets (ID 157)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K. Park, M. Villalona
- Coordinates: 9/09/2015, 18:30 - 20:00, Four Seasons Ballroom F3+F4
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MINI30.11 - Efficacy and Safety of Dovitinib in Advanced Squamous Cell Lung Cancer with FGFR1 Amplification: A Single-Arm, Phase II Study (ID 666)
19:30 - 19:35 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
FGFR1 amplification is one of the most common potential driving oncogenes in squamous cell carcinoma (SCC), which accounts for 20% of non-small cell lung cancer (NSCLC) squamous cell carcinoma. This phase II study evaluated the efficacy and toxicity profile of dovitinib, an orally active FGFR (fibroblast growth factor receptor) inhibitor, in advanced SCC patients.
Methods:
Patients with histological confirmed advanced squamous cell NSCLC and previously treated with at least one cytotoxic chemotherapy were enrolled from April 2013 to December 2014. All patients had FGFR1 gene amplification more than 5 copies by fluorescent in situ hybridization (FISH). Each 7-day treatment cycle consisted of dovitinib 500mg orally administration on days 1 to 5 and 2 days off. Primary endpoint was overall response rate and secondary endpoints included PFS, OS and toxicity.
Results:
All 26 patients were male with the median age of 68 years (range, 52 – 80). Most patients were ever smokers (96%) and had good ECOG (0-1) performance status (85%). The median number of dovitinib treatment cycles administered was 2.5 (range, 1-12). The overall response rate (ORR) was 11.5% (95% CI, 0.8 – 23.8) and disease control rate (DCR) was 50% (95% CI, 30.8 – 69.2). There were three partial responses (PR) and ten stable diseases (SD). Duration of response in 3 patients who achieved PR was 4.5+, 5.1+ and 6.1months. After the median follow-up duration of 15.7 months (range, 5.8 – 25.6 ), the median overall survival (OS) was 5.0 months (95% Confidential Interval, 3.61 – 6.39) and progression-free survival (PFS) was 2.9 months (95% CI, 1.54 – 4.26). Grade 1/2 fatigue (69%) and anorexia (85%) were most commonly reported adverse events and 12 patients (46%) required dose reduction of dovitinib.
Conclusion:
Dovitinib treatment a showed modest efficacy in advanced squamous cell lung cancer patients with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in SCC should be warranted.
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MINI 31 - ALK (ID 158)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:S. Malik, I. Ou
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 1a-1f
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MINI31.02 - Real-World Characteristics and Outcomes for ALK+ NSCLC in Korea (ID 535)
18:35 - 18:40 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Clinical trials have shown superior efficacy of ALK inhibitors compared with chemotherapies for patients diagnosed with ALK+ non-small cell lung cancer (NSCLC). In Korea, crizotinib was approved for ALK+ NSCLC in 2011 but is not yet reimbursed. The objective of this study was to describe real-world patient characteristics, ALK testing and treatment patterns, and survival among Korean patients diagnosed with locally-advanced or metastatic ALK+ NSCLC.
Methods:
A retrospective patient chart review was conducted in two major cancer centers in Korea. Participating physicians (N=4) reviewed patient charts and reported patient characteristics, ALK testing and treatment patterns, and survival of patients diagnosed with ALK+ locally-advanced or metastatic NSCLC. ALK inhibitor treatment duration and overall survival (OS) were estimated using Kaplan-Meier analyses.
Results:
In late 2014, 55 ALK+ NSCLC patients were identified for this study. The median follow-up time among these patients was 24.8 months. The median age at locally advanced or metastatic NSCLC diagnosis was 60 years (interquartile range: 52 - 67); 53% of patients were female, 51% were never-smokers, 2% were former smokers, 33% were current smokers, 15% had unknown smoking status, and 98% were diagnosed with adenocarcinoma. At primary diagnosis, 67% of patients had metastatic disease. ALK rearrangement was confirmed by fluorescent in situ hybridization (78%) or immunohistochemistry (22%). 27% of patients had their ALK rearrangement detected more than three months after their locally-advanced or metastatic diagnosis. The majority of patients received initial systemic chemotherapy; only 13% received an ALK inhibitor in the first-line, and 62% received an ALK inhibitor by the end of follow-up. Out of 30 patients who received crizotinib, 83% discontinued (median duration of 6.3 months) and 13% died while still on crizotinib. Of those who discontinued, 32% switched to chemotherapy, 16% switched to a different ALK inhibitor, and 52% received no further antineoplastic therapy. After discontinuing crizotinib, the median OS was 4.3 months.
Conclusion:
In this study of locally-advanced or metastatic ALK+ NSCLC patients in Korea, OS was poor following discontinuation of crizotinib with a median survival of 4.3 months. Additionally, many patients had delays in receiving ALK testing. Among patients who failed crizotinib treatment, over half received no further antineoplastic therapy. These findings suggest the need to provide timely access to ALK testing and effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.
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MINI31.13 - Symptoms and QOL with Ceritinib in ALK+ NSCLC Patients with/without Brain Metastases (ID 1655)
19:40 - 19:45 | Author(s): M. Ahn
- Abstract
Background:
In the pivotal ASCEND-1 study, ceritinib, an anaplastic lymphoma kinase inhibitor (ALKi), showed clinical activity in patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC), including in patients with brain metastases (BrM). Here, patient-reported outcomes (PROs) from the recently reported ASCEND-2 study (NCT01685060) are described for chemotherapy- and ALKi-pretreated patients with ALK+ NSCLC with and without baseline BrM
Methods:
In ASCEND-2, adult patients with ALK+ NSCLC previously treated with chemotherapy and an ALKi (crizotinib) received oral ceritinib 750 mg daily. PROs were assessed at baseline and Day 1 of treatment cycles 2, 3, and every two cycles thereafter (1 cycle=28 days), using the Lung Cancer Symptom Scale (LCSS) and EORTC quality of life and lung cancer surveys (QLQ-C30 and QLQ-LC13, respectively). Data were analyzed by presence/absence of baseline BrM. Data beyond cycle 9 are not reported due to small sample sizes.
Results:
All 140 patients enrolled (median age [range] 51 [29–80] years; 50.0% male), had received ≥2 antineoplastic regimens and 100 (71.4%) had BrM at baseline. At data cutoff (13 August 2014), median follow-up was 11.3 months. PRO questionnaire compliance was at least 91.2% up to cycle 9. In the overall patient population, investigator-assessed disease control rate (DCR) was 77.1% and median duration of response (DOR) 9.7 months. Investigator-assessed whole-body DCR [95% confidence interval (CI)] in patients with and without baseline BrM was 74.0% [64.3, 82.3] and 85.0% [70.2, 94.3], respectively, while DOR [95% CI] was 9.2 [5.5, 11.1] and 10.3 [7.4, 16.6] months, respectively. Analysis of PROs data demonstrated that treatment with ceritinib improved lung cancer symptoms in patients with and without baseline BrM (Figure). QLQ-LC13 outcomes were broadly consistent with those of LCSS. In general, mean global quality of life (QLQ-C30) was maintained on treatment for both patient subgroups, with mean change from baseline in QLQ-C30 global health status ranging from -3.06 to +7.25 in patients without baseline BrM and -2.83 to +3.55 in those with baseline BrM. Figure 1
Conclusion:
In patients with ALKi-pretreated ALK+ NSCLC who received prior chemotherapy and ceritinib, clinical efficacy was demonstrated and cancer symptoms were mostly improved, with health-related quality of life generally maintained regardless of presence or absence of baseline BrM.
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ORAL 11 - Clinical Trials 1 (ID 100)
- Event: WCLC 2015
- Type: Oral Session
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:A.K. Nowak, F. Detterbeck
- Coordinates: 9/07/2015, 10:45 - 12:15, 702+704+706
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ORAL11.06 - A Prospective Phase II Study of Cisplatin and Cremorphor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors: Can 18F-FDG PET/CT Play a Role? (ID 2221)
11:39 - 11:50 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
We conducted a prospective phase II study of cisplatin plus Cremorphor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors (TETs) in order to determine the efficacy and tolerability of the combination.
Methods:
Patients were treated with cisplatin (70 mg/m[2]) and Genexol-PM (230 mg/m[2]) every three weeks for a maximum of six cycles. The primary end point of this study was objective response rate (ORR), and secondary end points included toxicity, progression-free survival (PFS), overall survival (OS), correlation between early [18]F-FDG PET/CT response and PFS, and correlation between baseline FDG uptake and histology.
Results:
Forty-two patients with unresectable thymoma (n=14) or thymic carcinoma (n=28) were enrolled. The median age was 59 years (range, 25-77) and 30 (71%) patients were male, and 39 (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range 1-6). For 40 assessable patients, the ORR was 62.5% (95% confidence interval [CI] 47.6-77.4) with rates of 46% (95% CI 23.3-76.9) for advanced thymoma (n=13) and 70% (95% CI 52.0-82.1) for thymic carcinoma (n=27). With a median follow-up of 15.5 months, the median PFS was 9.8 months (11.4 months for thymoma vs. 8.1 months for thymic carcinoma, with median follow-ups of 16.1 vs. 15.5 months, respectively). The two-year OS was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Sixteen (38%) patients experienced grade 2 hypersensitivity reactions. There was no correlation between early PET response and PFS, but tumor histology (thymoma vs. thymic carcinoma) was correlated with SUV~max~ before chemotherapy.
Conclusion:
These data suggest that the combination of cisplatin and Genexol-PM is highly effective and tolerable for the treatment of unresectable TETs, especially in patients with thymic carcinoma.
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ORAL 16 - Clinical Care of Lung Cancer and Advanced Biopsies (ID 115)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J.W. Neal, Q. Zhou
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2a-3b
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ORAL16.05 - Retrospective Analysis of ctDNA EGFR Mutations in the Phase III, Randomized IMPRESS Study (ID 2106)
11:28 - 11:39 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
The majority of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer respond to first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs, e.g. gefitinib) but nearly all eventually acquire resistance. The most common mechanism of acquired resistance is a second-site mutation in the EGFR kinase domain, T790M. The phase III, double-blind IMPRESS study evaluated the efficacy and safety of continuing gefitinib plus pemetrexed/cisplatin versus placebo plus pemetrexed/cisplatin in patients with acquired resistance to first-line gefitinib. Study results did not support the continuation of gefitinib after disease progression (by RECIST criteria) when platinum-based doublet chemotherapy is used as second-line therapy. Here we report the results of a retrospective biomarker analysis of plasma circulating free, tumor-derived DNA (ctDNA) from patients in IMPRESS, including T790M profiling, to help understand the IMPRESS clinical trial outcome.
Methods:
Plasma samples for ctDNA isolation were collected at baseline and discontinuation from 151 randomized, non-Chinese patients in IMPRESS (58% of overall IMPRESS population). ctDNA levels of T790M, L858R, and Exon19 deletions were detected using both a quantitative emulsion (BEAMing) digital PCR assay (Sysmex[®]) and a qualitative QIAGEN[®] Therascreen ARMS assay (baseline only). Local EGFR tumor tissue (diagnostic) results were available for 133/151 patients. Mutation concordance rates between tissue and baseline plasma results, and comparisons between the two plasma detection methods, were calculated.
Results:
Baseline ctDNA EGFR mutation results were obtained for >99% (150/151) of patients. Using BEAMing, sensitivity and specificity between baseline plasma EGFR sensitizing mutations and local EGFR tumor tests were 78% (69/89) and 98% (42/43), respectively, for Exon19 deletions, and 82% (31/38) and 97% (91/94) for L858R. The T790M detection rate in baseline plasma samples using BEAMing was 56% (84/150). The Therascreen ARMS assay demonstrated a significantly reduced T790M detection rate of 13% (20/150). Likewise, the sensitivity of the Therascreen ARMS assay with respect to tissue for EGFR sensitizing mutations was also reduced compared with BEAMing: Exon 19: 54% (48/89), L858R: 47% (18/38), though the specificity remained near 100%. In the 97 evaluable plasma samples collected at discontinuation, T790M was detected by BEAMing in 52% (50/97) of patients. When compared with matched baseline plasma, 11 patients had newly acquired T790M mutation at discontinuation while T790M reverted to undetectable in 14 patients. Full plasma profiling data from the complete IMPRESS clinical study population (including 108 patients from China) and correlative analyses of plasma EGFR mutation status with clinical outcome (progression-free survival, overall survival, objective response rate) will be presented.
Conclusion:
In IMPRESS, T790M was detectable with BEAMing digital PCR in the baseline ctDNA samples of 56% of evaluable patients, a rate comparable to similar mutation analyses in this same second-line, EGFR-TKI-failed setting. EGFR mutation detection in plasma using the Therascreen ARMS assay demonstrated comparable specificity to BEAMing but reduced sensitivity. The T790M detection rate afforded by the BEAMing technology will allow for a comprehensive assessment of correlations between clinical outcome in IMPRESS and EGFR mutational status.
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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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ORAL17.08 - Gefitinib/Chemotherapy vs Chemotherapy in EGFR Mutation-Positive NSCLC Resistant to First-Line Gefitinib: IMPRESS T790M Subgroup Analysis (ID 3287)
12:01 - 12:12 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Exon 20 T790M mutation is the most common cause of acquired resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). The IMPRESS study (NCT01544179; Phase III, double-blind IRESSA[TM ]Mutation Positive Multicentre Treatment Beyond ProgRESsion Study; Lancet Oncology: in press) reported no statistically significant difference in progression-free survival (PFS; primary endpoint) between gefitinib plus cisplatin/pemetrexed (cis/pem) (G) vs placebo plus cis/pem (P) in patients with acquired resistance to first-line gefitinib (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.65–1.13; p=0.273; median PFS 5.4 months in both arms) and other secondary endpoints. Among the subgroup analyses performed for IMPRESS, the most noticeable difference was observed by T790M status as tested via plasma circulating free tumor-derived DNA (ctDNA).
Methods:
Patients (age ≥18 years [Japan ≥20 years], chemotherapy-naïve, locally advanced/metastatic NSCLC with an activating EGFR mutation, prior disease progression on first-line gefitinib) from 71 centers (Europe/Asia Pacific) were randomized to G or P (gefitinib 250 mg/day or placebo, plus cis 75 mg/m[2]/pem 500 mg/m[2]). For biomarker analysis, consenting randomized patients provided 10-mL blood samples (at Visit 1 [baseline], 4, 6; then every 6 weeks and at discontinuation) from which to obtain ctDNA. ctDNA levels of EGFR mutations, including T790M, were detected using a quantitative emulsion (BEAMing) digital PCR assay (Sysmex[®]) conducted at a central laboratory (positivity defined as ≥0.02% mutant DNA fraction).
Results:
Data are reported for plasma samples from baseline visits (serial data will be available in the future). Blood samples were available for all 261 randomized patients, of whom T790M status was known for 247 (93.2%): T790M mutation-positive n=142 (57.5%; G=81, P=61) and T790M mutation negative n=105 (42.5%; G=46, P=59). Median PFS for the T790M mutation-positive subgroup was 4.6 vs 5.3 months for G and P, respectively (HR 0.97, 95% CI 0.67 to 1.42, p=0.8829). Median PFS for the T790M mutation-negative subgroup was 6.7 vs 5.4 months for G and P, respectively (HR 0.67, 95% CI 0.43 to 1.03, p=0.0745). See Table for additional study endpoints.
Conclusion:
Following acquired resistance to first-line gefitinib, these data suggest there were two distinct patient populations defined by T790M genotype. For plasma T790M-positive, gefitinib should not be continued when platinum-based doublet chemotherapy is used as second-line therapy. For plasma T790M-negative, continuation of gefitinib in combination with platinum-based doublet chemotherapy may offer clinical benefit, which would require further confirmation in a prospective randomized study.IMPRESS subgroup populations (plasma) T790M mutation-positive N=142 T790M mutation-negative N=105 ORR, % (G vs P) 28.4 vs 39.3 p=0.282 37.0 vs 27.1 p=0.171 DCR, % (G vs P) 81.5 vs 77.0 p=0.5175 93.5 vs 83.1 p=0.0895 OS, HR (95% CI)* 2.16 (1.26, 3.82) p=0.0067 0.83 (0.36, 1.85) p=0.6644 Plasma BEAMing PCR (compared with tumor), % (n/N) Exon 19 Deletions L858R Sensitivity 73.8 (124/168) 81.6 (62/76) Specificity 96.7 (89/92) 95.3 (161/169) Concordance 81.9 (213/260) 91.0 (224/247) *OS immature, follow up ongoing G: gefitinib plus cisplatin/pemetrexed; P: placebo plus cisplatin/pemetrexed ORR, objective response rate; DCR, disease control rate; OS, overall survival
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ORAL 31 - PD1 Axis Inhibition (ID 143)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J. Weiss, B. Luey
- Coordinates: 9/09/2015, 16:45 - 18:15, Four Seasons Ballroom F1+F2
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ORAL31.02 - Pembrolizumab for NSCLC: Immune-Mediated Adverse Events and Corticosteroid Use (ID 3032)
16:56 - 17:07 | Author(s): M. Ahn
- Abstract
- Presentation
Background:
Pembrolizumab is a humanized monoclonal antibody against PD-1 that has demonstrated robust antitumor activity and a manageable safety profile in patients with advanced malignancies, including NSCLC. Similar to other immune checkpoint inhibitors, immune-mediated toxicities have been observed with pembrolizumab. We characterized the incidence of potentially immune-mediated adverse events (AEs) and the use of systemic corticosteroids for their management in patients with NSCLC treated with pembrolizumab in the phase 1 KEYNOTE-001 trial (ClinicalTrials.gov, NCT01295827).
Methods:
550 patients with advanced NSCLC received pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or 10 mg/kg every 2 weeks (Q2W). Potentially immune-mediated AEs were derived from a prespecified list and considered regardless of attribution to study treatment by the investigator. High-dose corticosteroid use was defined as an initial dose of ≥40 mg/day prednisone or equivalent. Low-dose corticosteroid use was defined as an initial dose of <40 mg/day prednisone or equivalent.
Results:
71 (12.9%) patients experienced ≥1 immune-mediated AE, including 17 (3.1%) who experienced grade 3-4 events, 1 (0.2) who died because of an immune-mediated AE (pneumonitis), and 14 (2.5%) who discontinued pembrolizumab because of immune-mediated AEs. The median time to onset of the first immune-mediated AE was 104 days (range, 2-393 days). Immune-related AE incidence was similar in patients treated with pembrolizumab 10 mg/kg Q2W and Q3W. The most common immune-mediated AEs were hypothyroidism, pneumonitis, and infusion-related reactions (Table). Pneumonitis was the most common grade 3-4 toxicity. Excluding hypothyroidism, 74.2% of immune-mediated AEs had resolved at the time of data cutoff. Of the 71 patients who experienced immune-mediated AEs, 30 (42.2%) received corticosteroids: 20 received high dose, 10 low dose. The highest incidence of corticosteroid use was for pneumonitis (84.2%) and colitis (80.0%) (Table). The duration of initial steroid use ranged from 1 to 129 days. Analyses related to the impact of steroid use on pembrolizumab efficacy are ongoing and will be available for presentation. Figure 1
Conclusion:
Potentially immune-mediated AEs, particularly those of grade 3-5 severity, are relatively infrequent in patients with advanced NSCLC treated with pembrolizumab. As evidenced by the low rate of pembrolizumab discontinuation, most immune-mediated events were managed by temporary pembrolizumab interruption and corticosteroid use.
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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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ORAL33.08 - Discussant for ORAL33.05, ORAL33.06, ORAL33.07 (ID 3372)
18:01 - 18:11 | Author(s): M. Ahn
- Abstract
- Presentation
Abstract not provided
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-037 - PD-L1 Expression in Surgically Resected Thymic Epithelial Tumor (ID 1488)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
Blockade of the immune checkpoint programmed death receptor ligand-1 (PD-L1)/PD-1 pathway has recently shown clinical activity across many tumor types. PD-L1 protein expression by immunohistochemistry (IHC) is emerging as a predictive biomarker of response to these therapies. Hence, we studied PD-L1 expression in a thymic epithelial tumor (TET).
Methods:
Of the patients who previously underwent resection of TET at Samsung Medical Center between January 2000 and January 2013, 220 patients who had available tissue block for immunohistochemistry were included. Formalin-fixed paraffin embedded tumor samples were stained with murine monoclonal antibody (clone h5H1) to human PD-L1. PD-L1 staining was classified based on intensity and moderate or strong intensity in 5% or more of tumor tissues was considered as positive PD-L1 expression.
Results:
The median age was 52 years (range, 18-81), and 57.7% of patients were male. WHO histologic type was mostly B2 (N=96, 43.6%), followed by C (N=48, 21.8%), B3 (N=47, 21.4%) and neuroendocrine tumor (N=17, 7.7%). R0 resection was possible in 193 patients (87.7%). Positive PD-L1 expression was observed in 83 samples (37.7%). PD-L1 expression and histologic type was significantly correlated, with high PD-L1 expression in histologic type B2/B3/C (7.1% vs. 42.4% in type A/AB/neuroendocrine tumor vs. type B2/B3/C; P<0.001). PD-L1 expression did not affect overall survival both in univariate and multivariate survival analysis.
Conclusion:
In TET, PD-L1 expression was positive in 37.7% and it was more frequently observed in aggressive histology (B2/B3/C). PD-1/PD-L1 targeting agents could be a promising therapy for TET.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-031 - Subgroup Analysis of East Asian Patients in the Phase III PROCLAIM Trial (ID 1293)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
PROCLAIM is a phase III trial comparing overall survival (OS) in patients with stage III, unresectable, nonsquamous non-small cell lung cancer (NSCLC) receiving pemetrexed (Pem) plus cisplatin (Cis) and concurrent thoracic radiation therapy (TRT) for 3 cycles followed by 4 cycles of Pem consolidation (Pem+Cis arm) versus etoposide (Etop) plus Cis and concurrent TRT for 2 cycles followed by up to 2 cycles of consolidation with a platinum-based doublet of choice (Etop+Cis arm). Overall efficacy and safety results for the intent-to-treat (ITT) population (N=598) will be presented in a separate disclosure. Efficacy and safety results from an East Asia (EA) subgroup analysis are presented here.
Methods:
A subgroup analysis was performed using the EA randomized population (N=97), which consisted of all patients who were randomized to the study from China (n=61), Taiwan (n=25), and The Republic of Korea (n=11). OS and progression-free survival (PFS) were evaluated by the Kaplan-Meier method and hazard ratios (HRs) were calculated using a Cox regression model. The log-rank test was used to compare treatment arms. Objective response rates (ORRs) were compared using an unadjusted, normal distribution approximation for the difference in rates. ClinicalTrials.gov number NCT00686959.
Results:
Baseline characteristics were balanced between treatment arms for EA patients. In the 97 randomized EA patients (n=44 in the Pem+Cis arm; n=53 in the Etop+Cis arm), median PFS was 10.0 months for the Pem+Cis arm and 7.6 months for the Etop+Cis arm (HR: 0.97, 95% confidence interval [CI]: 0.61–1.54, p=0.890). The censoring rate was high for OS (Pem+Cis arm: 43.2%; Etop+Cis arm: 52.8%), and there was no significant difference in OS between the Pem+Cis arm and the Etop+Cis arm (HR: 1.23, 95% CI: 0.70–2.14, p=0.469). The interaction test for region and treatment effect for OS was not significant (p=0.374). The ORRs were 47.7% (95% CI: 32.46–63.31) in the Pem+Cis arm and 34.0% (95% CI: 21.52–48.27) in the Etop+Cis arm. In the 90 treated EA patients (n=44 in the Pem+Cis arm; n=46 in the Etop+Cis arm), the overall incidence of drug-related grade 3/4 treatment-emergent adverse events (TEAEs) was significantly lower in the Pem+Cis arm versus the Etop+Cis arm (61.4% vs. 91.3%; p=0.001). All drug-related grade 3/4 TEAEs occurring in ≥5% of patients had a numerically lower incidence in the Pem+Cis arm than in the Etop+Cis arm except lymphopenia (17 [38.6%] vs. 17 [37.0%]).
Conclusion:
For EA patients with nonsquamous NSCLC, Pem+Cis did not improve OS, but did have a good safety profile and numerically improved PFS and ORR compared to Etop+Cis.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-004 - The BIM Deletion Polymorphism in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors (ID 1126)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant NSCLC.
Methods:
Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib).
Results:
The BIM deletion polymorphism was present in 15.6% (32/205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were < 65 years old (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar ORRs (91% vs. 84%, P = 0.585). Progression-free survival (PFS) and overall survival (OS) did not differ significantly between patients with and without the BIM deletion polymorphism (median PFS 12 vs. 11 months, P = 0.160; median OS 31 vs. 30 months, P = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including ECOG PS 0-1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients.
Conclusion:
It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-016 - Does Sequence of Cranial Radiotherapy Matter in EGFR Mutant Non-Small Cell Lung Cancer Patients with Brain Metastasis? (ID 2260)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
The incidence of brain metastasis in EGFR mutant advanced non-small cell lung cancer (NSCLC) is higher than EGFR wild type at the time of diagnosis. Although cranial radiotherapy is considered standard treatment for brain metastasis, EGFR tyrosine kinase inhibitors (TKIs) alone have shown promising activity with up to 80% of response in EGFR mutant NSCLC patients with brain metastasis. However, the role of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs remains to be determined.
Methods:
Advanced NSCLC patients harboring EGFR mutation (exon 19 deletion or L858R) with brain metastasis who were treated with EGFR TKIs were retrospectively reviewed. To investigate the role of cranial radiotherapy, we analyzed the clinical outcomes between patients treated with EGFR TKIs alone and those treated with cranial radiotherapy (WBRT or SRS) followed by EGFR TKIs (combination therapy). The primary end point was overall survival (OS) and secondary end points included intracranial and extracranial progression free survival (PFS).
Results:
A total of 573 patients who identified EGFR mutation and received EGFR TKIs treatment for NSCLC with brain metastasis from Jan 2007 to Dec 2013 at Samsung Medical Center were enrolled for analysis. Of all 573 patients, 121 patients had brain metastasis in initial work up. There were 38 males and 83 female, a median age was 59.5 years (range 30 – 80). All 121 patients were received gefitinib (n=103) or erlotinib (n=18) as EGFR TKI treatment for 1[st] line chemotherapy. 74 patients were treated with combination therapy (34 patients were taken SRS, 28 patients WBRT, 12 patients both), and 47 patients were treated with EGFR TKI alone. In combination therapy group, 32 patients had brain metastasis related symptoms.The median OS was 38.7 months [95% Confidence Interval 35.0 to 42.5] in combination therapy group and 28.6 months [95% CI 24.3 to 32.8] in EGFR TKI alone group (p=0.295). There were no significant differences in intracrainal PFS (18.6 vs 19.7 months, p=0.343) and extracranial PFS (15.7 vs 15.3 months, p=0.574) between two groups.
Conclusion:
In this retrospective analysis, the combination therapy with cranial radiotherapy followed EGFR TKI did not improve OS and intracranial PFS compared with EGFR TKI alone therapy in EGFR mutant NSCLC patients with brain metastases. Further prospective studies are needed to refine the role of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs.
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P3.01-077 - A Randomized, Phase II Study of Nimotuzumab Plus Gefitinib vs Gefitinib in Advanced Non-Small Cell Lung Cancer After Platinum- Based Chemotherapy (ID 1176)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody. We aim to evaluate the efficacy of dual inhibition of EGFR with nimotuzumab plus gefitinib in advanced non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
Methods:
An open label, randomized, phase II trial was conducted in 6 centers; 160 patients were randomized (1:1) to either nimotuzumab (200mg, IV weekly) plus gefitinib (250mg p.o. daily) or gefitinib alone until disease progression or intolerable toxicities. The primary endpoint was progression free survival (PFS) rate at 3 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR) and safety.
Results:
A total of 155 patients (78 in nimotuzumab plus gefitinib, 77 in gefitinib) were evaluable for efficacy and toxicity. Patient characteristics were well balanced in both groups. Majority of patients had adenocarcinoma histology (65.2%) and ECOG performance status 0 to 1 (83.5%). Among 102 patients with EGFR mutation results available, activating EGFR mutation was documented in 27 patients (12/50 in nimotuzumab plus gefitinib, 15/52 in gefitinib). With a median follow-up of 12.1 months, PFS rate at 3 months was 37.2% in nimotuzumab plus gefitinib and 48.1% in gefitinib [HR 1.03; 95% CI, 0.71–1.40; P=0.98]. Median PFS and OS were 2.0 months and 14.0 months in nimotuzumab plus gefitinib and 2.8 months and 13.2 months in gefitinib [HR 1.03, 95% CI 0.71-1.41, P=0.98 for PFS; HR 0.86, 95% CI 0.57–1.30, P=0.47 for OS]. The ORRs were 14.1% in nimotuzumab plus gefitinib and 22.1% in gefitinib, which was not statistically significant (P=0.76). As expected, patients with EGFR mutation showed significantly longer survival than those with wild-type EGFR or unknown EGFR mutation status (10.3 vs. 1.2 vs. 2.7 months, P < 0.001 for PFS; 23.5 vs. 13.5 vs. 10.5 months, P= 0.001 for OS). Combined treatment of nimotuzumab plus gefitinib did not show superior PFS compared to gefitinib alone in patients with EGFR mutation (13.5 vs. 10.2 months in gefitinib alone, P=0.30) and patients with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P=0.90). The median PFS was not significantly different between two treatment arms according to histology (2.8 vs. 2.9 months in gefitinib alone for adenocarcinoma, P=0.64; 1.2 vs. 2.8 months in gefitinib alone for non-adenocarcinoma, P=0.35). Adverse events (AEs) in both treatment arms were mostly grade 1 to 2 and easily manageable. Importantly, combined EGFR inhibition with nimotuzumab and gefitinib did not increase EGFR inhibition-related AEs, such as acneiform rash (32.4 vs. 30.3% in gefitinib alone, P=0.38), diarrhea (30.7 vs. 35.7% in gefitinib alone, P=0.32), and stomatitis (11.5 vs. 13.4% in gefitinib alone, P=0.19). There was no treatment-related death.
Conclusion:
The dual inhibition of EGFR with nimotuzumab plus gefitinib did not show superiority over gefitinib alone for second-line treatment of advanced NSCLC (NCT01498562).
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P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.03-001 - Comparison of Adjuvant Therapy Modes Following Resection in Lung Cancer Patients with Clinically (-) but Pathologically (+) N2 Disease (ID 1298)
09:30 - 09:30 | Author(s): M. Ahn
- Abstract
Background:
Mediastinal nodal staging is very important before recommending surgical resection in newly diagnosed non-small cell lung cancer patients. Following curative resection for having apparently clinically uninvolved mediastinal node (cN0-1), some proportion of patients, however, turns out to have pathologically involved mediastinal node (pN2). There have been controversies on optimal adjuvant therapy during past 2 decades in this clinical setting. Systemic chemotherapy, either followed by or concurrent with radiation therapy, has remained most important modality. This study is to evaluate clinical outcomes following similar, but different, 3 adjuvant therapy modalities, in all of which included systemic chemotherapy, at authors’ institute.
Methods:
Between 2006 and 2012, authors identified 240 cN0-1/pN2 patients who received adjuvant systemic chemotherapy following curative resection: chemotherapy alone in 85 patients (Group A); chemotherapy concurrent with thoracic radiation therapy (CCRT) in 68 (Group B); and CCRT followed by consolidation chemotherapy in 87 (Group C), respectively. Chemotherapy dose intensity was lower in CCRT setting than in upfront or consolidation chemotherapy settings, while thoracic radiation therapy dose schedule was the same (50 Gy/25 fractions). Clinical outcomes of loco-regional control (LRC), distant-metastasis free survival (DMFS) and overall survival (OS) were compared among Groups.
Results:
Median follow-up duration was 30 (5~93) months. Median age of all patients was 60 years and 149 patients (62.1%) were male. Majority of patients (224 patients, 93.3%) underwent lobectomy, while 16 (6.7%) did pneumonectomy. Adenocarcinoma was most common in 165 patients (68.8%) followed by squamous cell carcinoma in 53 (22.1%), and others in 22 (9.2%). There was no difference among Groups with respects to pretreatment and treatment characteristics except median age (Group A was older: 63 years vs. 58 years vs. 58 years, p=0.022). LRC, DMFS and OS rates at 5 years in all patients were 75.1%, 38.0% and 76.2%, respectively. Though no significant difference in OS at 5 years among Groups (76.8% vs. 68.4% vs. 82.5%, p=0.096), LRC rate at 5 years was significantly improved by addition of thoracic radiation therapy (62.9% vs. 78.9% vs. 82.9%, p=0.011), while DMFS rate at 5 years was significantly improved by delivering full dose chemotherapy (40.6% vs. 19.4% vs. 28.6%, p=0.018).
Conclusion:
Although in retrospective nature having potential selection bias, current observations support that maximal benefit could be achieved by thoracic radiation therapy concurrent with chemotherapy and consolidation full dose chemotherapy with respects to LRC and DMFS. Further prospective clinical trial would be desired.
