Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials.

Abstract

PURPOSE:

We previously reported preliminary activity of regorafenib plus nivolumab (REGONIVO) or lenvatinib plus pembrolizumab (LENPEM) in advanced gastric cancer (AGC). Meanwhile, several studies demonstrated liver metastases are less responsive to immunotherapy.

PATIENTS AND METHODS:

Combined efficacy outcomes with a longer follow-up in a phase Ib trial of REGONIVO and a phase II trial of LENPEM were examined in AGC with or without liver metastases (REGONIVO plus LENPEM cohort). We also investigated the efficacy of anti-PD-1 monotherapies (anti-PD-1 monotherapy cohort). A comparison of the immune microenvironment between gastric primary tumors and liver metastases was also conducted by multiplex IHC.

RESULTS:

In the REGONIVO plus LENPEM cohort, with a median follow-up of 14.0 months, objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were 46%, 7.8 months, and 15.6 months in patients with liver metastases, while 69%, 6.9 months, and 15.5 months in those without. In the anti-PD-1 monotherapy cohort, with a median follow-up of 27.6 months, ORR, mPFS, and mOS were 9%, 1.4 months, and 6.4 months in patients with liver metastases, while 22%, 2.3 months, and 9.0 months in those without. Multiplex IHC revealed liver metastases were associated with an abundance of immune-suppressive cells, such as tumor-associated macrophages and regulatory T cells, with fewer CD8+ T cells compared with gastric primary tumors.

CONCLUSIONS:

Anti-PD-1 antibodies plus regorafenib or lenvatinib for AGC showed promising antitumor activity with a longer follow-up, irrespective of liver metastases status, despite a more immune-suppressive tumor microenvironment in liver metastases.

• Authors: Hiroki Yukami, Akihito Kawazoe, Yi-Tzu Lin, Shohei Koyama, Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Masako Asayama, Takako Yoshii, Hideaki Bando, Daisuke Kotani, Yoshiaki Nakamura, Yasutoshi Kuboki, Saori Mishima, Masashi Wakabayashi, Takeshi Kuwata, Masahiro Goto, Kazuhide Higuchi, Takayuki Yoshino, Toshihiko Doi, Hiroyoshi Nishikawa, Kohei Shitara
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 16 Pg. 3480-3488 (08 15 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35679062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Nivolumab

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Clinical Trials as Topic
• Humans
• Immunotherapy
• Liver Neoplasms (drug therapy, secondary)
• Nivolumab (therapeutic use)
• Progression-Free Survival
• Stomach Neoplasms (drug therapy, pathology)
• Treatment Outcome
• Tumor Microenvironment