Abstract 709P
Background
In patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% to 49%, immune checkpoint inhibitor (ICI) combination chemotherapy is recommended, but the population for which chemotherapy has no additional immune checkpoint inhibitor benefit is not known.
Methods
We conducted a retrospective cohort study included patients with advanced or recurrent NSCLC with PD-L1 TPS expression of 1% to 49% diagnosed across 19 institutions in Japan. All patients initiated platinum-doublet chemotherapy with or without ICI between March 2017 and June 2022. Propensity score matching (PSM) was used to align patient characteristics and assess efficacy and safety between treatments. Factors that did not improve overall survival (OS) in the ICI plus chemotherapy group were examined using Cox proportional hazards models.
Results
Of 851 patients, median age was 70 years [range 36-89], 643 (75%) male, performance status 0 or 1 in 786 (93%) cases, and adenocarcinoma in 529 (62%) cases, and 504 (59%) received ICI plus chemotherapy and 347 (41%) received chemotherapy. In the overall post-PSM cases, median progression-free survival (PFS) and OS were significantly prolonged with ICI plus chemotherapy compared to chemotherapy alone (PFS: HR 0.61, P<0.001; OS: HR 0.77, P=0.01). Multivariate analysis revealed significantly shorter OS with ICI plus chemotherapy when antibiotics (ATB) were administered (P=0.02). The median PFS and OS were not significantly different between ICI plus chemotherapy and chemotherapy alone in patients who received ATB (PFS: HR 0.63, P=0.09; OS: HR 0.74, P=0.24), while those who did not receive ATB had significantly prolonged PFS and OS with ICI plus chemotherapy (PFS: HR 0.60, P<0.001; OS: HR 0.75, P=0.02). Adverse events above grade3 were increased in patients with prior antibiotics therapy.
Conclusions
Antimicrobial therapy for advanced NSCLC patients with PD-L1 TPS of 1% to 49% attenuates the effect of ICI combination chemotherapy and increases treatment-related adverse events.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T. Yamada: Financial Interests, Institutional, Funding: Ono Pharmaceutical, Janssen, AstraZeneca, Takeda Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai-Roshe. T. Kijima: Financial Interests, Personal, Other: Chugai Pharmaceutical Co., MSD KK. S. Watanabe: Financial Interests, Institutional, Funding: Boehringer Ingelheim, Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Lilly, Novartis Pharma, Chugai Pharma, Bristol-Myers, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Kirin, Merck, Takeda Pharmaceutical, Celltrion, AstraZeneca. H. Taniguchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharma. T. Fukui: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer-Ingelheim Japan Inc, Chugai Pharmaceutical Co, Eli Lilly Japan, Nippon Kayaku Co; Financial Interests, Personal, Other: Novartis Pharma K.K., Ono Pharmaceutical Co., Pfizer Japan. K. Kaira: Financial Interests, Institutional, Funding: Ono Pharmaceutical Company, Chugai Pharmaceutical, Bristol-Myers Company, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Okada: Financial Interests, Personal, Other: Chugai-Roshe, AstraZeneca, Boehringer Ingelheim, Eli Lilly Japan, Nippon Kayaku, Bristol Myers Squibb. K. Takayama: Financial Interests, Institutional, Funding: Chugai Pharmaceutical Co., Ono Pharmaceutical ; Financial Interests, Personal, Funding: AstraZeneca, Chugai Pharmaceutical Co., MSD-Merck, Eli Lilly, Boehringer Ingelheim, Daiichi Sankyo. All other authors have declared no conflicts of interest.