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H. Nechushtan
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MA 02 - Emerging Targets (ID 656)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Ravi Salgia, Shun Lu
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 511 + 512
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MA 02.06 - BRAF Mutant NSCLC: Correlation with PD-L1 Expression,TMB, MSI and Response to ICPi and Anti-BRAF Therapy (ID 10473)
11:35 - 11:40 | Author(s): H. Nechushtan
- Abstract
- Presentation
Background:
The efficacy of immune check-point inhibitors (ICPi) in BRAF mutant non-small cell lung cancer (NSCLC) is largely unknown. The correlation with different parameters predicting efficacy of ICPi (e.g., PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability status (MSI) in these tumors needs further evaluation.
Method:
A retrospective analysis of 30 patients with BRAF mutant advanced NSCLC treated between Aug 2013 and May 2017 was performed. The patients were divided into 2 groups: BRAF V600 E (Group A, N=16), non-V600E BRAF (Group B, N=14). PD-L1 was assessed by immunohistochemistry using 22C3 Dako antibody clone on Dako or Ventana's platform in 16 patients. TMB and MSI were assessed in 9 and 11 patients, respectively. Median progression-free survival (mPFS) with ICPi and targeted agents as well as median overall survival (mOS) were assessed in each group by Kaplan-Meier method.
Result:
Baseline characteristics of the cohort: median age 66y (range 39-98); males 53%; current/past smokers/never smokers/NA 13%/44%/40%/3%; adenocarcinoma/other histology 80%/20%; ECOG PS 0/1/2/3/4/NA 27%/33%/10%/13%/0%/17%. The distribution of TMB, PD-L1 expression and MSI status between the 2 groups is presented in Table 1. Ten patients received ICPi (nivolumab-8, pembrolizumab-2), and thirteen patients received anti-BRAF therapy (dabrafenib+trametinib-6, dabrafenib-4, vemurafenib-3). mOS and mPFS with ICPi and anti-BRAF therapy are summarized in Table 1. Four patients with BRAF V600 E PD-L1 ≥ 50% tumors were included in the series; one patients responded to dabrafenib+trametinib combination (response ongoing, 7.1months+); in two patients ICPi were initiated, response assessment pending. One patient with a non-V600E BRAF mutant NSCLC responded to dabrafenib for 6.7 months.Figure 1
Conclusion:
BRAF mutant NSCLC tumors are associated with high level of PD-L1 expression, low/intermediate TMB and MSI stable status. ICPi may induce prolonged responses both in BRAF V600E and non-V600E BRAF mutant NSCLC. Some non-V600E BRAF mutant NSCLC may benefit from anti-BRAF targeted therapy.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-056 - Intracranial Activity of Osimertinib in Naïve EGFRm T790M(-)And Treated EGFRm T790M(+) NSCLC Patients with Asymptomatic Brain Metastases (ID 9819)
09:30 - 09:30 | Author(s): H. Nechushtan
- Abstract
Background:
Osimertinib is an effective, irreversible EGFR-TKI selective for EGFR-TKI-sensitizing (EGFRm) and T790M[+] resistance mutations. Intracranial activity of osimertinib has been reported in T790M[+] patients; however its activity in EGFR-TKI naïve setting has not been investigated yet. Here, we present preliminary data of a phase II study assessing the intracranial activity of osimertinib in EGFRm NSCLC patients with asymptomatic brain metastases as 1[st] line therapy for naïve patients and as 2[nd] line therapy for EGFRm patients who progressed on EGFR TKI and harbor T790M[+]. Dose escalation from 80 mg QD to 160 mg QD was allowed in cases of brain progression.
Method:
A phase II, open label, two arm study is presented. Treatment-naïve (arm A) advanced NSCLC with sensitizing EGFRm and previously treated (arm B) with 1[st] or 2[nd]-generation EGFR TKIs (gefitinib, erlotinib or afatinib) in whom T790M[+] was diagnosed were enrolled to this study. Intracranial response was assessed by brain MRI scans every 6 weeks and systemic evaluation by PET-CT scan every 3 months unttil progression. The study plans to enroll 20 patients in each arm aiming to reach a statistical power of 0.8.
Result:
As of May 31 2017, 22 patients were enrolled; 15 patients in arm A and 7 patients in arm B, age 67.8±10.4 years, 14 females and 8 males. Preliminary outcome analysis is presented for 16 patients with a median follow up of 6.1 months (range 1.4-11.4 months). On May 31[st] 2017 data cut-off was performed. The Intracranial response rate (ICRR) was 81% (13/16 pts); 82% (9/11 pts) in arm A and 80% (4/5 pts) in arm B. Time to response was 6 weeks (1[st] MRI) in all responding patients. Intracranial disease control rate (IDCR) was 81% (13/16 pts) for the current follow up time of 6.1 months; median PFS not reached. Dose escalation was performed in 2 cases and data is not mature yet. Toxicity profile is similar to previous reported data.
Conclusion:
Osimertinib shows a promising intracranial response rate in naïve EGFRm NSCLC patients (82% ICRR) and in 2[nd] line T790M (+) setting with 80% ICRR. This study is still recruiting.
