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Radj Gervais
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OA12 - Novel Therapies in MET, RET and BRAF (ID 921)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 106
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OA12.03 - Activity of Crizotinib in MET or ROS1 Positive (+) NSCLC: Results of the AcSé Trial. (ID 12937)
15:35 - 15:45 | Author(s): Radj Gervais
- Abstract
- Presentation
Background
Crizotinib was registered for ALK+ NSCLC in 2013 and recently for ROS1+ stage IV NSCLC. To generate high evidenced-based knowledge and to prevent off-label use, the French National Cancer Institute (INCa) launched the AcSé Program: equal access to tumor molecular diagnosis including an exploratory phase II trial. AcSé allows nationwide safe and controlled access to crizotinib off-label.
a9ded1e5ce5d75814730bb4caaf49419 Method
Biomarkers were identified with INCa molecular genetic platforms. Patients with amplification [amp] MET or mutation [mut] MET or translocation [tlc] ROS1 advanced NSCLC and not eligible for any other trial, were proposed crizotinib 250 mg BID. Tumor response was evaluated every 2 months (mo) using RECIST v1.1. The primary endpoint was the objective response rate (ORR) at 2 mo (complete + partiale response). A two-stage Simon design was applied to each cohort. Median and 95% confidence interval (CI) was estimated through Kaplan-Meier for progression-free survival (PFS), overall survival (OS), and response duration. Response duration was the delay between CR/PR and first progression/death or last follow-up.
4c3880bb027f159e801041b1021e88e8 Result
From 08/2013 to 03/2018, 5407 patients from 186 centers entered the biomarker program. Tumor alterations found in patients were: ROS1 tlc in 77/4050; MET amp (≥6 copies/diploid genome) in 251/4171; MET mut in 76/1007.
Overall, 90 patients (median age, 63 years [30–92]) received crizotinib 250 mg BID.
73 grade ≥3 adverse events (AEs) or SAE were reported in 70/90 patients. Grade ≥3 AEs were: hematologic toxicities (23%) including neutropenia (11%), and general disorders (16%) including fatigue (10%).
8eea62084ca7e541d918e823422bd82e Conclusion
This study confirms the excellent response rate of crizotinib in the ROS1+ population. Response rate in the MET mut population is comparable to the MET amp population. In addition, the response rate to crizotinib in the MET mut population is lower than that in the PROFILE 1001 study. The tolerance profile is good as previously reported.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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OA12.05 - Vemurafenib in Patients Harboring V600 and Non V600 BRAF Mutations: Final Results of the NSCLC Cohort from the AcSé Trial. (ID 12936)
16:00 - 16:10 | Author(s): Radj Gervais
- Abstract
- Presentation
Background
BRAF mutations are found in 2-3% of NSCLC. BRAF inhibitors reportedly have antitumor activity. The French National Cancer Institute (INCa) launched a program giving nationwide access to vemurafenib for cancer patients with BRAF-mutated tumors and supported molecular screening. We herein report the NSCLC cohort results.
a9ded1e5ce5d75814730bb4caaf49419 Method
BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Patients with mutated BRAF (V600E and others mutations) progressing after ≥1 standard treatment were proposed vemurafenib 960 mg BID. Objective Response Rate (ORR) was assessed using RECIST v1.1 every 8 weeks. A sequential Bayesian approach was planned to allow early stopping using an inefficacy bound for ORR of 10%. If no early stopping occurred, the treatment was considered worthy for further evaluation if there was a 90% probability that the estimated ORR is ≥30%, the efficacy bound.
4c3880bb027f159e801041b1021e88e8 Result
From 10/2014 to 10/2017, 118 NSCLC patients were enrolled: 101 with BRAF V600E and 17 with other potentially activating mutations (4 G466, 4 G469, 1 G596, 5 K601, and 3 N581). Median age was 68 years (range 34–85), 71% smokers, 48% females, 100% non-squamous histology, and 20% with ECOG PS 2. Most frequent grade ≥3 adverse events (AEs) were asthenia (9% of patients), epidermoid carcinoma (6%), dermatitis (5%), and increased GGT (5%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia, and 1 neutropenic sepsis.
Nine patients were still on treatment at the cut-off date, 106 had stopped vemurafenib (65 PD, 26 AEs, 3 deaths, 1 doctor’s decision, 11 patient’s decisions).
8eea62084ca7e541d918e823422bd82e Conclusion
Vemurafenib provided reasonable response rate and extended PFS in pretreated NSCLC patients with BRAF V600E mutations but was not effective in those with other BRAF mutations. These results emphasize the need of integrating BRAF V600E in routine biomarkers screening.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-31 - Efficacy and Tolerance of Immune-Checkpoint Inhibitors in EGFR, ALK/ROS 1 Non-Small-Cell-Lung-Cancer (NSCLC): GFPC 03-2016 IMAD Study (ID 11166)
16:45 - 18:00 | Author(s): Radj Gervais
- Abstract
Background
Patients with molecular alterations are considered to be poor candidates for immune- checkpoint inhibitors (ICI) on the second-line phase III trials. Here, we analyze the efficacy of ICI in EGFR /ALK/ROS1 NSCLC patients in real world setting
a9ded1e5ce5d75814730bb4caaf49419 Method
This retrospective, multicentric study in EGFR, ALK and ROS1 NSCLC treated by ICI, analyzed clinical characteristics and outcomes (progression free survival (PFS), duration of ICI treatment and overall survival (OS), since initiation of ICI .
4c3880bb027f159e801041b1021e88e8 Result
51 patients were included from 20 centers in France: 100% adenocarcinoma, 60.7% never smokers, 58.8% female, 58 ± 8.8 years age at diagnosis (36-83), 82.3% EGFR mutated, 15.7 % and 2% ALK and ROS 1 translocated respectively. ICI was a third line treatment in 35,3% of cases, a fourth and more lines treatment in 64,7% of cases. Median PFS was 2.1. [95% CI: 1.5-3.2] months for the whole population, 2.15 [95% CI: 1.4-3;2], for EGFR patients and 2.4 [95% CI: 2.1; NR] for ALK tranlocated patients; 3 months-PFS were 37,3% [95% CI: 26.1; 53.2]; 8 weeks ORR were 19.6% (10 pts with partial response). The median OS for the whole population was 14.7.[95%CI: 12.1-19.2] months, 13.9 [95% CI: 8.8-20] for EGFR patients, 19.2. [95% CI: 13.1-NR] for ALK translocated; 7 (13.7%) patients were treated more than 9 months by ICI; 21.6% (11/51) of patients reported toxicities, all < grade3.
8eea62084ca7e541d918e823422bd82e Conclusion
In this real-world setting analysis, efficacy of ICI in EGFR, ALK, ROS1 NSCLC patients appears close to the efficacy observed in pretreated unselected NSCLC patients. Large prospective studies are needed in these populations
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-02 - PD-L1 Expression Pattern in Large Cell Neuroendocrine Carcinoma of the Lung: The GFPC 03-2017 "EPNEC" Study. (ID 11945)
16:45 - 18:00 | Author(s): Radj Gervais
- Abstract
Background
Large cell neuroendocrine carcinomas of the lung (LCNECs) are rare neoplasms with few therapeutics options especially for stage IV diseases. Pathological diagnostic of LCNECs may be difficult with low interobserver reproducibility and need immunohistochemical (IHC) staining. Immune checkpoint inhibitors targeting tumoral and immune cells interaction have revolutionized the treatment of NSCLC, but few data's are available on LCNECs immune environment and particulary the expression of PD-L1 on both tumors (TC) and immune infiltrating (IC) cells. The objective of the present study is to determine the pattern of PD-L1 staining in a cohort of LCNECs patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Clinical files and tumors biopsies of patients (pts) with a LCNEC diagnosed between 01.01.2014 and 31.12.2016 were retrospectively collected (GFPC 03-2017). All histological samples were centrally reviewed by a panel of six independent pathologists, according to the WHO 2015 classification. LCNEC was confirmed and PD-L1 expression was determined both in TC and IC, using the anti-PD-L1 antibody 22C3 (kit and automat Dako). PD-L1 expression was scored on TC as the percentage of PD-L1 positive cells (0 to 100%). PD-L1 expression on IC was determined as follows: IC0: positive IC representing<1% of the tumor surface; IC1: positive IC representing>=1% but<5% of the tumor surface; IC2: positive IC representing>=5% but<10% of the tumor surface; and IC3: positive IC representing>10% of the tumor surface.
4c3880bb027f159e801041b1021e88e8 Result
Eighty-six pts were initially included in the study.Twenty-eight (32%) of them were excluded for non-LCNEC diagnosis after review. Among the 58 remaining pts with confirmed LCNEC, five (8%) had a mixed histology with a NSCLC component.The mean age of the population was 65 years, mainly mens (86%) and former or current heavy smokers (93%). Fifty-five and 51 tumors samples were respectively available for TC and IC PD-L1 IHC expression. PD-L1 expression on TC was found in only 12% of the samples (7/55), while 76% (39/51) of the samples shows IC PD-L1 positive, with respectively 18 (35%) IC3, 8 (14%) IC 2, and 13 (25%) IC1.
8eea62084ca7e541d918e823422bd82e Conclusion
Histological diagnosis of LCNEC remains difficult, and prospective studies concerning patients with LCNEC should include a centrally pathological review of tumors.The PD-L1 expression pattern looks different for LCNEC in comparison to other lung carcinomas, as few TC were found positive although IC were frequently positive, half of the tumors having high PD-L1 IC infiltration (IC3/2). This PD-L1 pattern may suggest a potential effectiveness of therapeutic anti PD-L1 antibodies and this hypothesis have to be adressed in clinical trials.
6f8b794f3246b0c1e1780bb4d4d5dc53
