Abstract 645P
Background
Immune checkpoint inhibitors (ICIs) are widely utilized in various cancers, including non-small-cell lung cancer (NSCLC). However, the impact of different driver gene alterations on the efficacy and safety of ICIs remains unclear. This study aims to investigate how the type of driver gene alteration affects the efficacy of ICI alone or in combination with platinum doublet chemotherapy.
Methods
This retrospective, multicenter study analyzed clinical data from NSCLC patients harboring alterations in ALK, ROS1, BRAF, MET, KRAS, RET, HER2, or NTRK. The study compared the efficacy of ICI plus combined with platinum doublet chemotherapy or platinum doublet chemotherapy alone, focusing on best response, progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs).
Results
Among 902 patients, distribution of alterations included 356 with ALK fusion, 88 with ROS1 fusion, 59 with BRAF V600E mutation, and others. Patients with MET exon 14 skipping mutations and BRAF V600E mutations had a higher percentage of PD-L1 TPS ≥50%. Conversely, 48.8% of those with HER2 mutations were PD-L1 TPS negative. The median PFS for patients with ALK fusion receiving ICI plus platinum doublet chemotherapy was 6.9 months (95%CI: 4.4-12.7) compared to 7.5 months (95%CI: 5.0-10.8) for platinum doublet chemotherapy alone (p=0.75). On the other hand, in patients with BRAF V 600E mutation and KRAS mutation, ICI plus platinum doublet chemotherapy showed improved efficacy compared with platinum doublet chemotherapy alone in terms of PFS (BRAF V600E: 12.7 months (95%CI: 4.2-NA) vs 6.6 months (95%CI: 0.8-10.5) HR 0.34 [95%CI 0.14-0.85], (p=0.016) (KRAS: 8.8 months (95%CI: 6.9-11.4) vs 5.4 months (95%CI: 4.3-8.7) HR 0.60 [95%CI 0.43-0.82], (p=0.001). No new types of irAEs were reported, and the frequency of irAEs was similar between those receiving sequential therapy with cytotoxic and targeted agents post-ICI.
Conclusions
For patients with KRAS and BRAF mutations, combining ICI with platinum doublet chemotherapy significantly extended PFS compared to platinum doublet chemotherapy alone. Some patients with other genetic alterations also exhibited prolonged benefits from ICI therapy.
Clinical trial identification
UMIN000049022; 20th, 2022.
Editorial acknowledgement
Legal entity responsible for the study
NEJSG.
Funding
Novartis Pharma KK.
Disclosure
A. Mouri: Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical Co. T. Shukuya: Financial Interests, Institutional, Local PI: AstraZeneca, Chugai pharmaceutical co. ltd, MSD, Novartis, Eli Lilly, Takeda pharmaceutical, Nippon Kayaku; Financial Interests, Institutional, Research Funding: AstraZeneca, Chugai pharmaceutical, MSD, Novartis, Eli Lilly, Takeda pharmaceutical, Nippon Kayaku; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, Eli Lilly, Ono Pharmaceutical, Merck, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb, Eisai, Nippon Kayaku, Amgen, AstraZeneca, Chugai pharmaceutical, MSD, Novartis. T. Tsuda: Financial Interests, Institutional, Research Funding: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co., Ltd. H. Ashinuma: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Merck, Chugai pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, Takeda pharmaceutical, Eli Lilly, MSD, Nippon Kayaku, Daiichi Sankyo pharmaceutical. H. Tanaka: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co. Ltd, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical Co, Boehringer-Ingelheim Japan Inc, Pfizer Japan Inc, Takeda, Amgen. S. Takahashi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb Japan, Chugai Pharma, Kyowa Kirin, MSD, Taiho Pharmaceutica, Takeda. S. Watanabe: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai pharmaceutical co. ltd, Lilly, Novartis, Bristol-Myers, Ono Pharmaceutical, Daiichi Sankyo, Celltrion, Takeda Pharmaceutical, Taiho Pharmaceutical, MSD; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Chugai. Y. Tsukita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Lilly, MSD, Eisai, Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Bristol Myers Squibb, Nippon Boehringer Ingelheim. Y. Tamura: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD K.K., Chugai Pharmaceutical Co.,LTD, AstraZeneca K.K. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Amgen K.K, Bristol Myers Squibb Company, Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K, MSD K.K, Ono Pharmaceutical Co. Ltd., Sanofi K.K. K. Kobayashi: Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Zeria Pharmaceutical Co.; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. M. Maemondo: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Company, Bristol Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Chugai pharma; Financial Interests, Personal, Local PI: Ono Pharma, AstraZeneca, Chugai pharma. All other authors have declared no conflicts of interest.