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C. Audigier-Valette
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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: 1
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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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): C. Audigier-Valette
- 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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ORAL 03 - New Kinase Targets (ID 89)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:F. Blackhall, R. Juergens
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 4a-4f
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ORAL03.06 - Activity of Crizotinib in MET Amplified NSCLC: Preliminary Results of the AcSé Trial (ID 1200)
11:39 - 11:50 | Author(s): C. Audigier-Valette
- Abstract
- Presentation
Background:
Crizotinib (crz) is registered only for the treatment of patients (pts) with ALK-translocated lung cancer. Crz is also a MET inhibitor. MET is amplified in several malignancies. Activity of crz in MET amplified (+) tumors was explored as part of the French National Cancer Institute (INCa) AcSé program, including both access to tumor molecular diagnosis and an exploratory multi-tumor 2-stage design phase II trial. We report here results in pts with MET + NSCLC.
Methods:
MET analysis on formalin-fixed, paraffin-embedded tumor samples was proposed in 170 investigating centers and performed in 28 regional INCa molecular genetic centers. MET+ was explored by FISH in tumor samples showing an IHC score of ≥2+. Pts with a tumor showing > 6 MET copies, whatever the MET/CEN7 ratio, were eligible, providing they were not eligible for any other academic or industry trial evaluating another MET inhibitor. Study treatment consisted in crz 250 mg BID. The objective response rate (ORR) and disease control rate (DCR) were assessed every 8 weeks, using RECIST v1.1.
Results:
From Aug. 5, 2013 to Mar. 1, 2015, 25 pts with MET+ NSCLC were enrolled and received crz. Median age was 59 years (range 30–92). Forty-four percent were females, 92% had tumors of non-squamous histology, and 96% presented with metastatic disease at study entry. Median number of prior treatments was 2 (range 0 – 11). Eight pts were still on treatment at the cut-off date, 17 have stopped crz (15 progressive diseases (PD), 1 adverse event (AE), 1 patient’s choice). Among the 18 pts evaluable for response after 8 weeks, we observed 7 partial responses, 6 stable diseases and 5 PD, leading to an ORR of 39% [95% CI:17-64], and a DCR of72% [47-90]. DCR at 6 months was 22% (4 pts out of the 18 evaluable pts). Crz was well tolerated with only 5 grade ≥3 (2 AE + 3 SAEs) and 3 grade 1-2 SAEs. Most common AEs, mainly grade 1 or 2, were nausea (60% of pts), visual disorders (52%), anemia (52%), elevated transaminases (48%) and vomiting (40%).
Conclusion:
Nationwide biomarker-driven access to crz for pts with MET+ malignancy is feasible. Crz was well tolerated and showed responses in pretreated MET+ lung cancers. Survival data and duration of response will be presented.
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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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ORAL11.01 - Bevacizumab 15mg/kg Plus Cisplatin-Pemetrexed (CP) vs CP in Malignant Pleural Mesothelioma (MPM): IFCT-GFPC-0701 MAPS Randomized Phase 3 Trial (ID 2142)
11:07 - 11:18 | Author(s): C. Audigier-Valette
- Abstract
Background:
MPM median overall survival (OS) did not exceed 13 months with pemetrexed-platinum doublet, with virtually no surviving patients at 5 years. Vascular endothelial growth factor is a potent mitogen for MPM cells.
Methods:
In this French multicenter randomized phase 3 trial, eligible patients had unresectable, histologically proved MPM, age < 76, no prior chemo, PS 0-2, no thrombosis, nor bleeding. Randomized patients (1:1) received pem 500 mg/m2, CDDP 75 mg/m2 at D1, with (arm B) or without bevacizumab (arm A), 15 mg/kg Q21D, for 6 cycles. Arm B non-progressive patients received bevacizumab maintenance therapy until progression or toxicity. Primary endpoint was OS. 445 patients were to be randomized, and 385 events observed, to show a significant OS improvement, with 80% statistical power, 5% a-risk.
Results:
From Feb. 2008 to Jan. 2014, 448 patients were included in 73 centers. Males: 75.4%, median age: 65.7 years (range 34.7-75.9), PS 0-1: 96.7%. The IDMC recommended a second interim analysis after 85% of events. On 01-Jan-2015, the duration since last news was < 30 days in 105 out of 106 still living patients. Overall survival was significantly longer in the experimental arm (median: 18.8 months, 95%CI[15.9-22.6] vs. 16.1 months, 95%CI[14.0-17.9] for the reference arm, (adj.HR = 0.76, 95%CI[0.61; 0.94], p = 0.012). With only 46/448 non-progressive patients at the date of analysis, median PFS was 9.6 months, 95%CI[8.5-10.6] in bevacizumab arm vs. 7.5 months, 95%CI[6.8-8.1] (adj.HR = 0.62, 95%CI[0.50-0.75], p < 0.0001). G3-4 hematological toxicities did not significantly differ in the two arms (49.5% vs. 47.3%). Significantly more G3 proteinuria (0.0 vs. 3.1%), G3 hypertension (0.0 vs. 23%), G3-4 arterial thrombotic events (0.0 vs. 2.7%) were observed in bevacizumab arm. QOL and exploratory biomarkers studies will be also presented at time of the meeting.
Conclusion:
Bevacizumab addition to pemetrexed/cis-platin provides a significantly longer survival in pts with MPM, with acceptable toxicity, making this triplet a new treatment paradigm.
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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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ORAL33.01 - Crizotinib Outcome and Post-Progression Management in ALK+ NSCLC: IFCT-1302 CLINALK (ID 1355)
16:45 - 16:56 | Author(s): C. Audigier-Valette
- Abstract
- Presentation
Background:
Phase III trials have demonstrated the superiority of the ALK tyrosine kinase inhibitor (ALK-TKI) crizotinib compared to standard chemotherapy in advanced ALK positive non-small cell lung cancers (ALK+ NSCLC) in first line and second line setting. Objective response rate (ORR) with crizotinib ranged from 65 to 75% and median progression free survival (PFS) from 7.7 to 10.9 months. However a resistance to crizotinib always occurs. The French Cooperative Thoracic Intergroup (IFCT)-1302 CLINALK study aimed to describe clinical outcome and post-progression management in a large cohort of French patients with ALK+ NSCLC treated with crizotinib.
Methods:
IFCT-1302 CLINALK is a multicentric observational retrospective study. Patients with ALK+ NSCLC from centers of the IFCT network were included according to the main following criteria: advanced stage III or stage IV NSCLC, ALK immunochemistry (IHC) and/or ALK FISH positivity, crizotinib treatment in the setting of the French expanded access cohort program or as approved drug. Epidemiological and clinical data, crizotinib efficacy (objective response based on RECIST, PFS, overall survival (OS)), duration of treatment with crizotinib after disease progression and post progression outcome were collected on a case report form. The study inclusion period was from November 18 2011 to December 31 2013. The data cut-off was December 31 2014.
Results:
318 patients were included (median age 58.3, female 49.4%, caucasian 98.6%, non-smoker 55.1%, performance status 0/1 78.7%, adenocarcinoma 91.7%, stage III 14.5%, stage IV 85.5%, brain metastasis 35.9%). IHC was positive in 151/173 patients and FISH in 279/283 patients. Before crizotinib treatment, patients received platinum-based chemotherapy in 89% of cases and pemetrexed-based chemotherapy in 76.1%. Crizotinib was prescribed as first-line treatment in 17 patients (5.3%), second-line in 168 patients (52.8%), third-line in 58 patients (18.2%) and more than third-line in 75 patients (23.7%). Objective response was complete response in 1 patient (0.3%), partial response in 126 patients (40.0%), stable disease in 62 patients (19.7%) and progression in 58 patients (18.4%). ORR was 40.3 % (95%CI, 34.9-45.7). 262/318 patients presented progressive disease (82.4%) at time of analysis. Median PFS was 6.9 months (95%CI, 5.7-8.6). Median OS with crizotinib was 18.7 months (95%CI, 15.2-22.5). Median duration of treatment with crizotinib after disease progression was 56 days (29-203). Among 143 patients with subsequent treatments, crizotinib was rechallenged in 32 patients (22.4%). 58/143 patients (40.6%) were treated after crizotinib failure with another ALK-TKI, either alectinib (19/58, 32.8%) or ceritinib (40/58, 69.0%). The ALK-TKI sequence was crizotinib-alectinib in 18 patients, crizotinib-ceritinib in 39 patients and crizotinib-alectinib-ceritinib in 1 patient.
Conclusion:
This retrospective study of 318 patients with ALK+ NSCLC showed a remarkable efficacy of crizotinib, with a 18.7 months median OS, a 40.3% ORR and a 6.9 months median PFS. However, ORR and mPFS were lower than those reported in phase III trials, which may be due to less stringent selection criteria. Analysis of predictive factors of response and survival including post-progression strategies will be presented.
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