VOLTAGE-B study: Nivolumab monotherapy and subsequent curative surgery following preoperative chemoradiotherapy in patients with locally recurrent rectal cancer (LRRC) without previous radiotherapy.

100 Background: Chemoradiotherapy (CRT) followed by curative resection in patients (pts) with local recurrence after radical surgery for primary rectal cancer is the preferred strategy if radiotherapy (RT) was not previously performed. In VOLTAGE-A study, nivolumab plus surgery following CRT showed a promising pathologic complete response (pCR) rate of 30% in pts with microsatellite-stable (MSS) advanced primary rectal cancer. The treatment sequence was prospectively investigated in pts with Locally Recurrent Rectal Cancer (LRRC) in VOLTAGE-B. Methods: Pts with pelvic LRRC without previous RT were included. Five cycles of nivolumab (240 mg q2 weeks) plus curative surgery following CRT (50.4 Gy with capecitabine 1,650 mg/m 2 ) were performed. The pCR rate using AJCC tumor regression grading and curative resection rate were key endpoints. Planned sample size in VOLTAGE-B was set 10 pts in an exploratory manner. Results: From May to Oct 2018, 10 pts were included. Median age was 65 and 8 were male. Curative resection was performed in nine pts with MSS. One had a newly diagnosed supraclavicular lymph node metastasis before surgery. As one pt with AJCC grade 0, seven with grade 2, and one with grade 3, were observed, pCR rate was 10%. As of cut-off date of Apr 2019, three pts showing recurrence out of the nine pts were observed. Nivolumab-related adverse events (AEs) were only one pt with grade 1 hyperthyroidism and one with grade 1 erythema. Grade 3/4 surgery-related AEs were observed in six pts, including two pts with ileus and two with pelvic infections. No treatment-related deaths were observed. Conclusions: The pCR rate of 10% with acceptable toxicity was shown in MSS LRRC pts treated with nivolumab plus curative surgery following CRT. Translational research exploring better predictors of efficacies of study treatment are ongoing. Clinical trial information: NCT02948348.