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

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 YoshidaYutaka Suzuki, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Preoperative chemoradiotherapy (CRT) and surgical cohorts, respectively. While immune-related severe adverse events resection are the standard treatment for locally advanced rectal were observed in 3 patients, no treatment-related deaths were cancer (LARC). Combining immune checkpoint inhibitors with observed. In 38 patients with MSS who underwent surgery, pCR radiation suggests a promising approach for enhancing efficacy. We rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were investigated the efficacy of CRT followed by nivolumab and surgery observed in those with programmed cell death ligand 1 (PD-L1) in patients with LARC. tumor proportion score ≥1% and <1%, respectively; IHC staining Patients and Methods: In phase I, we investigated the feasibility was performed using pre-CRT samples. In 24 patients with of sequentially combined CRT, 5 cycles of nivolumab, and radical MSS, pre-CRT samples were analyzed by flow cytometry; pCR surgery. In phase II, patients with microsatellite stable (MSS) and rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) microsatellite instability-high (MSI-H) LARC were evaluated. were observed for CD8þ T cell/effector regulatory T cell (CD8/Results: Three patients in phase I received full courses of CRT eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating and nivolumab without dose modification; the schedule was recomlymphocytes. mended for phase II. A pathologic complete response (pCR) was Conclusions: CRT followed by consolidation nivolumab could centrally confirmed in 30% [11/37; 90% confidence interval (CI), increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio 18%–44%] and 60% (3/5) of the MSS and exploratory MSI-H were positive predictors in patients with MSS LARC.

Original languageEnglish
Pages (from-to)1136-1146
Number of pages11
JournalClinical Cancer Research
Volume28
Issue number6
DOIs
Publication statusPublished - Mar 15 2022
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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