Abstract 250P
Background
Total neoadjuvant therapy (TNT) is the new cornerstone in the treatment of locally advanced rectal cancer (LARC), resulting in better complete pathologic response (pCR) and disease-free survival (DFS). However, the increased local recurrence rate (LRR) with short-course radiotherapy (SCRT) is concerning. The synergistic effect of immunotherapy with radiotherapy may improve pCR and reduce LRR even in microsatellite stable (MSS) tumors. We present the final analysis of the Averectal trial that aimed to evaluate the safety and efficacy of SCRT followed by chemotherapy and avelumab then total mesorectal excision (TME).
Methods
This is an investigator initiated, open label, single arm, multicenter, phase II study. Patients with LARC received SCRT, 6 cycles of mFOLFOX-6 plus avelumab, followed by TME. The primary outcome is the pCR rate compared to a historical control. Secondary outcomes are 3-year DFS, Immunoscore (IS: mean density percentiles of CD3 and CD8 positive T cells infiltrating the tumor and in the invasive margin of the tumor), safety, and quality of life (QOL).
Results
From July 2018 to October 2020 44 patients were accrued. 40 patients completed the treatment and are included in the analysis. 65% are males and median age is 58.5 (31.0, 74.0) years. All patients are MSS. Median follow-up is 44 months (11.4, 51.4). 15 patients (37.5%) achieved pCR as compared to the historical control group with pCR of 16% (p=0.025) and 67.5% had a major pathologic response. Mean DFS is 42 months (37.9, 46.1) and mean OS is 46.3 months (44.4, 48.2). Median DFS and OS are not reached. The 3-year DFS rate is 85%, and LRR is 1/40 (2.5%). Patients with pCR had significantly higher mean IS compared to those with no pCR (68 vs. 52, p = 0.036). As for safety, 77/327 (23.5%) adverse events were serious, out which 68.8% were Grade3/4 and only 1 was related to avelumab. Death occurred in 3/40 (7.5%) patients due to disease progression. QOL assessment showed no deterioration at the last follow up compared to baseline.
Conclusions
The addition of avelumab to neoadjuvant SCRT, FOLFOX and TME significantly improved pCR rate without increasing LRR, and with acceptable toxicity and QOL.
Clinical trial identification
NCT03503630.
Legal entity responsible for the study
The authors.
Funding
Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945), under a previous alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer.
Disclosure
All authors have declared no conflicts of interest.