Study Recommends Preoperative CRT Followed By Nivolumab, Radical Surgery for MSS and MSI-High Advanced Rectal Cancer

Study findings suggest that a regimen comprising nivolumab and radical surgery after chemoradiotherapy should be a candidate therapy for patients with locally advanced, microsatellite stable (MSS) and microsatellite instability–high (MSI-H) colorectal cancer (CRC).

The short-term results of the VOLTAGE trial were presented at the 2020 ESMO World Congress on Gastrointestinal Cancer.

“Chemoradiotherapy (CRT) followed by radical surgery is the standard therapy for patients with locally advanced rectal cancer (LARC). Sequential use of an anti-PD-1 antibody after radiation demonstrates synergistic effects in in vivo models, and an anti-PD-1 antibody is effective in patients with [MSI-H] metastatic [CRC],” wrote Satasho Yuki, MD, Hokkaido University Hospital, Sapporo, Japan and co-investigators on what led them to study nivolumab and radical surgery after chemoradiotherapy in T3-4 LARC.

Patients enrolled in this investigator-initiated study received pre-operative chemoradiotherapy with capecitabine followed by 5 cycles of nivolumab before surgery.

A total of 39 patients were enrolled in the microsatellite-stable arm and 5 patients were enrolled in the microsatellite-instable high arm.

The primary end point was pathological complete response (pCR) in patients with microsatellite-stable locally advanced rectal cancer.

Of those enrolled, 38 patients in the MSS arm and 5 patients in the MSI-H arm, respectively, received surgical resection. One patient refused surgical resection after achieving a clinical complete response.

Three patients experienced immune-related severe adverse events (grade 3 myasthenia, grade 3 interstitial nephritis, and grade 2 peripheral motor neuropathy). All patients recovered, and no treatment-related deaths were observed.

“Pathological complete response was observed in 30% of MSS patients. In patients with MSI-High, 60% pathological complete response was observed,“ Dr. Yuki stated during the virtual 2020 ESMO World Congress on Gastrointestinal Cancer presentation.

They noted PD-L1 expression and elevated CD8/eTreg ratio may be a better predictor of pCR, according to a biomarker analysis performed.

Researchers suggested the VOLTAGE regimen is a candidate therapy for future non-surgical approach.—Kaitlyn Manasterski

Yuki S, Bando H, Tsukada Y, et al. Short-term results of VOLTAGE-A: Nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stability and microsatellite instability-high, locally advanced rectal cancer (EPOC 1504). Presented at: the 22nd ESMO World Congress on Gastrointestinal Cancer; July 1-4, 2020; virtual. Abstract SO-37.