Avelumab (PD-L1) + neoadjuvant chemoradiotherapy delivers 74.7% 4-year PFS in high-risk LARC (AVANA)

Avelumab is an anti–PD-L1 immune checkpoint inhibitor added to standard neoadjuvant long-course chemoradiotherapy (CTRT) for locally advanced rectal cancer, aiming to deepen response before surgery. In the multicenter, single-arm Phase II AVANA trial (NCT03854799), high-risk LARC patients (cN+, cT4, or high-risk cT3; n=101) received CTRT + 6 cycles avelumab then surgery, achieving pCR 21.8% (22/101); at median follow-up 51.8 months, 48-month PFS was 74.7% (95% CI 65.0–82.2) and 48-month OS was 87.6% (95% CI 79.1–92.7) with 26 progression events and 13 deaths. Against typical long-course CRT pCR rates of ~15–20%, this pCR looks roughly in-range, and it trails modern TNT benchmarks where pCR is often ~28% in high-risk populations (e.g., RAPIDO/PRODIGE-23), while the abstract does not report grade ≥3 immune-related toxicities or CTRT tolerability/discontinuation—an important omission for a regimen that could add immune AEs on top of pelvic CRT.