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

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 CD8^þ 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.