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Céline Mahier - Ait Oukhatar
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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): Céline Mahier - Ait Oukhatar
- 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.
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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): Céline Mahier - Ait Oukhatar
- 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.
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