Elizabeth Dudnik1, Nir Peled2, Hovav Nechushtan3, Mira Wollner4, Amir Onn5, Abed Agbarya6, Mor Moskovitz7, Shoshana Keren8, Noa Popovits-Hadari8, Damien Urban9, Moshe Mishaeli10, Alona Zer11, Aaron M Allen12, Natalie Maimon Rabinovich10, Ofer Rotem11, Teodor Kuznetsov9, Tzippy Shochat13, Laila C Roisman14, Jair Bar5. 1. Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. Electronic address: elizabetadu@clalit.org.il. 2. Soroka University Medical Center, The Cancer Institute, Beer-Sheva, Israel; Ben Gurion University of the Negev, Beer-Sheva, Israel. 3. Oncology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 4. Thoracic Cancer Unit, Rambam Health Care Campus, Haifa, Israel; The Technion, Israeli Institute of Technology, Technion City, Haifa, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Thoracic Oncology Unit, Institute of Oncology, Sheba Medical Center, Tel HaShomer, Israel. 6. Oncology Department, Bney Zion Medical Center, Haifa, Israel. 7. Thoracic Cancer Unit, Rambam Health Care Campus, Haifa, Israel. 8. Oncology Department, Lin Medical Center (associated with Carmel Hospital), Haifa, Israel. 9. Thoracic Oncology Unit, Institute of Oncology, Sheba Medical Center, Tel HaShomer, Israel. 10. Oncology Department, Meir Medical Center, Kfar Sava, Israel. 11. Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. 12. Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 13. Statistical Consulting Unit, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. 14. Soroka University Medical Center, The Cancer Institute, Beer-Sheva, Israel.
Abstract
INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown. METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed. RESULTS: High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018). CONCLUSIONS: BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC.
INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown. METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed. RESULTS: High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018). CONCLUSIONS:BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAFV600E and BRAF non-V600E mutant NSCLC.
Authors: Sarah Abou Alaiwi; Amin H Nassar; Wanling Xie; Ziad Bakouny; Jacob E Berchuck; David A Braun; Sylvan C Baca; Pier Vitale Nuzzo; Ronan Flippot; Tarek H Mouhieddine; Liam F Spurr; Yvonne Y Li; Taiwen Li; Abdallah Flaifel; John A Steinharter; Claire A Margolis; Natalie I Vokes; Heng Du; Sachet A Shukla; Andrew D Cherniack; Guru Sonpavde; Robert I Haddad; Mark M Awad; Marios Giannakis; F Stephen Hodi; X Shirley Liu; Sabina Signoretti; Cigall Kadoch; Matthew L Freedman; David J Kwiatkowski; Eliezer M Van Allen; Toni K Choueiri Journal: Cancer Immunol Res Date: 2020-04-22 Impact factor: 11.151
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