Addition of mFOLFOX6 and Avelumab to Neoadjuvant Therapy Improves Outcomes in Locally Advanced Microsatellite Stable Rectal Cancer

According to results from the phase 2 Averectal study, the addition of mFOLFOX6 and avelumab to neoadjuvant short-course radiotherapy, followed by total mesorectal excision, improved outcomes among patients with locally advanced microsatellite stable (MSS) rectal cancer.

“Total neoadjuvant therapy has improved complete pathologic response rate and disease-free survival (DFS) in locally-advanced rectal cancer, though an increased local recurrence rate with short-course radiotherapy is concerning,” stated Ali Shamseddine, MD, American University of Beirut Medical Center, Beirut, Lebanon, et al. “Synergism between immunotherapy and radiotherapy may improve outcomes in [locally-advanced rectal cancer], even where [MSS] tumours exist.”

In this open-label, single-arm study, 40 patients received short-course radiotherapy (5 Gy in 5 fractions) plus 6 cycles of mFOLFOX-6 and avelumab once every 2 weeks followed by total mesorectal excision. The primary end point was complete pathological response. Key secondary end points included DFS, overall survival (OS), local recurrence rate, safety, and the association between ImmunoScore with pathological response. 

At a median follow-up of 44 months, 37.5% of patients achieved complete pathological response and 67.5% of patients achieved a major pathological response. Median DFS and OS were not achieved, however the mean DFS was 42 months, and the mean OS was 46.3 months. The 3-year DFS rate was 85% and the local recurrence rate was 2.5%. Mean ImmunoScore was 68 for patients who achieved pathological response and 52 for patients who did not achieve pathological response (P = .036). Serious adverse events occurred in 23.5% of patients and 3 patients died due to disease progression. 

“Adding avelumab to neoadjuvant chemotherapy mFOLFOX6 after [short-course radiotherapy], followed by [total mesorectal excision], improved [complete pathological response] without increasing [local recurrence rate], with acceptable toxicity and [quality of life],” concluded Dr Shamseddine et al. 

Source: 

Shamseddine A, Turfa R, Chehade L, et al. Short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced microsatellite stable rectal adenocarcinoma: The Averectal study. Eur J Cancer. Published online: April 22, 2025. doi: 10.1016/j.ejca.2025.115428