Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer.

BACKGROUND

The efficacy and safety of chemotherapy (CTx) after anti-PD-1 therapy in patients with advanced gastric cancer (AGC) remains unclear.

METHODS

Medical records of consecutive patients with AGC treated with both CTx (taxanes plus ramucirumab, taxanes monotherapy or irinotecan) and anti-PD-1 therapy from June 2015 to April 2019 were retrospectively analysed. Patients were divided into two groups based on prior exposure to anti-PD-1 therapy: anti-PD-1-exposed and anti-PD-1-naïve groups. CTx-related outcomes were compared between two groups in the overall population and each CTx population.

RESULTS

In total, 233 patients (67 anti-PD-1-exposed, 166 anti-PD-1-naïve) were included. In the overall population, the objective response rate (ORR) to CTX was 44.6% in the anti-PD-1-exposed group and 19.6% in the anti-PD-1-naïve group (p=0.001); the median progression-free survivals (PFS) were 3.7 months and 3.3 months (HR=0.82, p=0.20), respectively. Among patients receiving taxanes plus ramucirumab (n=149), ORR (60.6% vs 20.0%, p<0.001) and median PFS (4.8 vs 3.4 months, p=0.004, HR=0.56) were significantly better in the anti-PD-1-exposed group (n=39) compared with the anti-PD-1-naïve group (n=110). These differences were not observed in patients receiving taxane monotherapy (n=34) or irinotecan (n=50). CTx after anti-PD-1 therapy showed no severe or unexpected adverse events.

CONCLUSIONS

Prior anti-PD-1 therapy might increase tumour response to taxanes plus ramucirumab without unexpected adverse events, which warrants further investigations in a large cohort.

Informations de copyright

© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Déclaration de conflit d'intérêts

Competing interests: AK reports research funding from Ono, Sumitomo Dainippon and Taiho. TE, MO, SM and KS have nothing to disclose. YN reports research funding from Ono pharmaceutical and Taiho Pharmaceutical. DK reports receiving honoraria from Takeda, Chugai, Lilly, Merck Serono, Taiho and Sysmex. YK reports a consulting or advisory role for Takeda; personal fees from Bayer, Lilly, Taiho, MSD and Sanofi; and research funding from Astra Zeneca, Daiichi-Sankyo, Incyte, Taiho, Ono, Boehringer Ingelheim, Chugai, Amgen, Genmab and Takeda. HT reports grants and personal fees from Takeda, personal fees from Taiho, personal fees from Chugai, grants from Sysmex, grants from Daiichi-Sankyo. TK reports personal fees from MSD; and research funding from Astellas, Bristol-Myers Squibb, MSD, Oncolys BioPharma, Ono, Shionogi. TD reports a consulting or advisory role for AbbVie, Amgen, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Sumitomo Dainippon, Rakuten Medical, Taiho and Takeda; honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Oncolys Biopharma, Ono and Taiho; and research funding from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Kyowa Hakko Kirin, Lilly, Merck Serono, MSD, Novartis, Pfizer, Quintiles, Sumitomo Group and Taiho. TY reports a consulting or advisory role for Chugai, Lilly, Merck Serono and Sanofi; honoraria from Chugai, Takeda, Eli Lily, Merck Biopharma; and research funding from Chugai, GlaxoSmithKline, MSD, Nippon Boehringer Ingelheim, Novartis, Sanofi, Ono, Daiichi-Sankyo, Parexel and Sumitomo Dainippon. KS reports paid consulting or advisory roles for Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono and MSD; honoraria from Novartis, AbbVie and Yakult; and research funding from Astellas, Lilly, Ono, Sumitomo Dainippon, Daiichi-Sankyo, Taiho, Chugai, MSD and Medi Science.