Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

Abstract

PURPOSE:

Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC.

PATIENTS AND METHODS:

In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated.

RESULTS:

Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes.

CONCLUSIONS:

CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.

• Authors: Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Yosuke Togashi, Shohei Koyama, Daisuke Kotani, Shota Fukuoka, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Makoto Fukui, Masashi Wakabayashi, Naoki Nakamura, Motohiro Kojima, Hiroshi Kawachi, Richard Kirsch, Tsutomu Yoshida, Yutaka Suzuki, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 6 Pg. 1136-1146 (03 15 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35063964 (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

• B7-H1 Antigen
• Nivolumab

Topics

• B7-H1 Antigen (genetics)
• Chemoradiotherapy
• Humans
• Microsatellite Instability
• Microsatellite Repeats (genetics)
• Neoadjuvant Therapy
• Nivolumab (therapeutic use)
• Rectal Neoplasms (drug therapy, therapy)