Abstract 1548P
Background
Platinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear.
Methods
We retrospectively reviewed post-surgical limited-stage (LS)-SCLC and ES-SCLC patients treated with atezolizumab plus carboplatin and etoposide (ACE). The association between SCLC subtypes based on transcriptomic data and pathological findings, including CD8-positive tumor-infiltrating lymphocyte (TIL) status, was investigated in the LS-SCLC cohort. The association between the efficacy of ACE therapy, pathological subtypes, and TIL status was evaluated in the ES-SCLC cohort.
Results
The LS-SCLC cohort (N=48) was classified into four SCLC subtypes (ASCL1+NEUROD1 [SCLC-A+N, N=17], POU2F3 [SCLC-P, N=15], YAP1 [SCLC-Y, N=10], and inflamed [SCLC-I, N=6]) based on transcriptomic data. SCLC-I showed enriched immune-related pathways, the highest immune score (CD8A expression and T-cell–inflamed gene expression profiles), and epithelial–mesenchymal transition (EMT), in transcriptional subtypes. Immunohistochemical staining showed that SCLC-I in transcriptional subtypes had the highest density of CD8-positive TILs within the tumor microenvironment. In the ES-SCLC cohort, the efficacy of ACE therapy did not differ according to pathological A/N/P/Y subtypes. However, the progression-free survival (PFS) of TILHigh patients was significantly longer than that of TILLow patients (PFS: 7.3 months vs. 4.0 months, p<0.001).
Conclusions
Pathological subtypes did not predict the efficacy of ACE therapy. However, tumors with a high density of TILs, which represent the most immunogenic SCLC subtype (SCLC-I), based on transcriptomic data could benefit from ACE therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Japan Science and Technology Agency (JST) CREST (JPMJCR1689 to RH), JSPS KAKENHI (Grant Number 18K07036, 21K06900), the YokoyamaFoundation for Clinical Pharmacology and AIP-PRISM (JPMJCR18Y4 to RH).
Disclosure
T. Yoshida: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol-Myers Squibb , Takeda. Y. Matsumoto: Financial Interests, Personal, Research Grant: National Cancer Center Research and Development Fund, Grant-in-Aid for Scientific Research on Innovative Areas, Hitachi, Ltd.; Financial Interests, Personal, Invited Speaker: Olympus, AstraZeneca, Novartis. K. Masuda: Financial Interests, Personal, Invited Speaker: Chugai. Y. Shinno: Financial Interests, Personal, Research Grant: Ono, Janssen, Clinical Research Operations K.K; Financial Interests, Personal, Invited Speaker: BMS, Chugai, AstraZeneca, Eli Lilly, Ono. Y. Goto: Financial Interests, Personal, Research Grant: Eli Lilly, Taiho Pharmaceutical, Pfizer, Novartis, MSD, Guardant Health, Ono Pharmaceutical, Kyorin, Daiichi Sankyo, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho Pharmaceutical, Pfizer, Novartis, MSD, Chugai, Boehringer Ingelheim, AstraZeneca, Dai-ichi Sankyo, Bristol Myers Squibb, Guardant Health, Ono Pharmaceutical, Illumina. H. Horinouchi: Financial Interests, Personal, Research Grant: MSD, AbbVie, AstraZeneca, BMS, Ono, Merck Biophama, Daiichi-Sankyo, Janssen, Genomic Helath, Chugai, Roche, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eli Lilly, Ono, BMS, Chugai, Roche, Ono, BMS, MSD. T. Tsuchida: Financial Interests, Institutional, Research Grant: Japan Agency for Medical Research and Development, Foundation for Promotion Cancer Research; Financial Interests, Personal, Expert Testimony: Nippon Medical SchoolFoundation . R. Hamamoto: Financial Interests, Institutional, Research Grant: JST AIP-PRISM (Grant Number JPMJCR18Y4). N. Yamamoto: Financial Interests, Personal, Research Grant: Chugai, Taiho, Eisai, Lilly, Quintiles, Astellas, BMS, Novartis, Daiichi-Sankyo, Pfizer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Bayer, Ono Pharmaceutical Co, Ltd, Takeda, Janssen Pharma, MSD, Merck, Sysmex, GSK, Sumitomo Dainippon, Chiome Bioscience Inc, Otsuka, Genmab, Shionogi, Carna Biosciences; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co, Ltd, Chugai, AstraZeneca, Pfizer, Lilly, BMS, Sysmex, Eisai; Financial Interests, Personal, Advisory Board: Eisai, Otsuka, Takeda, Boehringer Ingelheim, Cimic. Y. Ohe: Financial Interests, Personal, Research Grant: AstraZeneca, Chugai, Lilly, Ono, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi-Sankyo, Janssen, Loxo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Ono, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc.. All other authors have declared no conflicts of interest.