Abstract 1211P
Background
The standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is platinum-based definitive chemoradiotherapy (dCRT). However, complete response (CR) rates are low (11–25%), with a median survival of 9–10 months. Sequential immunotherapy after dCRT has shown improved efficacy in patients with locally advanced non-small cell lung cancer.
Methods
We investigated the efficacy and safety of 1-year atezolizumab treatment following 60 Gy of dCRT in patients with unresectable locally advanced ESCC. Patients with primary locally advanced ESCC (primary cohort) and postoperative locoregionally recurrent ESCC (exploratory cohort) after dCRT were included. The primary endpoint was confirmed CR (cCR) rate, and we confirmed CR twice by both CT and endoscopy with ≥4-week intervals. The required sample size of the primary cohort was 38, with a threshold cCR rate of 20%, an expected rate of 40%, power of 80%, and one-sided alpha of 5%.
Results
Fifty patients were enrolled, with 40 and 10 in the primary and exploratory cohorts, respectively. The cCR rate of the first 38 patients was 42.1% (90%CI 28.5%–56.7%), and the primary endpoint was met. The cCR rates of the primary and exploratory cohorts were 40.0% and 50.0%, respectively. In the primary cohort, the median progression-free survival (PFS) and 12-month PFS rate were 3.2 months and 29.6%, respectively, and the median overall survival (OS) and 12-month OS rate were 31.0 months and 65.8%, respectively. In 35 patients with an evaluable PD-L1 tumor proportion score, the cCR rates of <1% and ≥1% were 44.4% and 41.2%, respectively. Multiplexed immunohistochemistry of 38 evaluable patients indicated significantly higher tumor-infiltrating CD8+ T cells and PD-1+CD8+ T cells before dCRT in 15 patients with cCR than in 23 without cCR (p=0.0002 and 0.0020, respectively). No new safety concerns or treatment-related deaths were reported.
Conclusions
Atezolizumab monotherapy following dCRT resulted in a promising cCR rate and led to promising long-term survival. Tumor-infiltrating CD8+ T cells and PD-1+CD8+ T cells can serve as biomarkers for cCR.
Clinical trial identification
UMIN000034373 Release date is Nov 1st, 2018.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study is supported by Japan Agency for Medical Research and Development (AMED). Chugai pharmaceutical provided the atezolizumab. Chugai pharmaceutical also support the translational research of this study.
Disclosure
H. Bando: Financial Interests, Institutional, Research Grant: Ono pharmaceutical; Other, Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. T. Tsushima: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Takeda, Taiho Pharma, Ono Pharmaceutical, MSD; Financial Interests, Institutional, Invited Speaker: Taiho Pharma, MSD, Ono Pharmaceutical, BeiGene, Chugai Pharmaceutical. H. Hara: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Boehringer Ingelheim, Dainippon Sumitomo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Kyowa Hakko Kirin, Lilly, Merck Biopharma, Sanofi, Taiho, Takeda, Yakult; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayel, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Merck Biopharma, MSD, Ono, Taiho. S. Kadowaki: Financial Interests, Personal and Institutional, Research Grant: Taiho, Eli Lilly, MSD, Ono, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Chugai, Nobel Pharma, Yansen; Financial Interests, Personal, Invited Speaker: BMS, Bayer, Merck Serono, Eisai. K. Kato: Financial Interests, Personal, Invited Speaker: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, Beigene, Taiho, Merck Biophrma, Amgen, Novartis; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: ONO Pharmaceuticals, Merck & Co, BAYER, AstraZeneca, Beigene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. H. Nishikawa: Financial Interests, Personal, Invited Speaker: Ono pharmaceutical, BMS, Chugai, MSD; Financial Interests, Institutional, Research Grant: Ono pharmaceutical, Kyowa Kirin, Sysmex, Taiho, Daiichi Sankyo, Zenyaku, Asahi Kasei, Chugai, BMS, Becton Dickison Japan, Asteras, SRL, Rakuten Medical, Fujifilm, Dainippon Sumitomo, Hitachi, MSD, Oncolys BioPharma, Debiopharm Group, MiraBiologics. T. Kojima: Financial Interests, Institutional, Principal Investigator: BeiGene Ltd., MSD K.K., Amgen Inc., Shionogi & co., Ltd., Ono Pharmaceutical Co., LTD., Chugai Pharmaceutical Co., LTD., Taiho Pharmaceutical Co., LTD., Parexel International; Financial Interests, Institutional, Research Grant: EPS Corporation. Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ono Pharmaceutical Co., LTD., Covidien Japan, Inc., MSD K.K., Taiho Pharmaceutical Co., LTD.; Financial Interests, Personal, Writing Engagements: MSD K.K.; Financial Interests, Personal, Advisory Board: Merck Biopharma Co., Ltd. All other authors have declared no conflicts of interest.