The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Yohei KubotaKohei Shitara

Abstract

We evaluated the association between molecular subtypes of advanced gastric cancer (AGC) and the efficacy of standard chemotherapy or immune checkpoint inhibitors. Patients with AGC who received systemic chemotherapy from October 2015 to July 2018 with available molecular features were analyzed. We investigated the efficacy of standard first- (fluoropyrimidine + platinum ± trastuzumab) and second-line (taxanes ± ramucirumab) chemotherapy, and subsequent anti-PD-1 therapy in patients with four molecular subtypes: MMR-D (mismatch repair deficient), EBV+, HER2+, and all negative. 410 patients were analyzed: MMR-D 5.9%, EBV+ 4.1%, HER2+ 13.7%, and all negative 76.3%. In 285 patients who received standard first-line chemotherapy, the median progression-free survival (PFS) times were 4.2, 6.0, 7.5, and 7.6 months and the objective response rates (ORR) were 31%, 62%, 60%, and 49% in MMR-D, EBV+, HER2+, and all-negative subtypes, respectively. Multivariate analysis showed shorter PFS in MMR-D versus all-negative patients [HR, 1.97; 95% CIs, 1.09-3.53; P = 0.022]. In second-line setting, there were no significant differences in efficacy. In 110 patients who received anti-PD-1 therapy, median PFS times were 13.0, 3.7, 1.6, and 1.9 months...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Pharmacology·Xiaohao ZhengYibin Xie
Aug 11, 2020·Journal of Immunology Research·Siru Nie, Yuan Yuan
Nov 27, 2020·Japanese Journal of Clinical Oncology·Akihito KawazoeMasanori Terashima
Jan 20, 2021·Nature Reviews. Cancer·Shogo KumagaiHiroyoshi Nishikawa
Nov 13, 2020·Visceral Medicine·Angelica Petrillo, Elizabeth C Smyth

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