The Ave-Rec trial: Phase II trial of PDL1/PD-1 blockade with Avelumab post Chemoradiotherapy for locally advanced resectable T3B-4/N1-2 Rectal cancer.
Type: article
Abstract: Purpose Long course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in 10-30% pathological complete response rate (pCR). Radiotherapy is both immuno-stimulatory and -suppressive. PDL1-inhibition may enhance its immuno-stimulatory effects. Hypothesis Avelumab given post-LCCRT may increase tumor response rates whilst reducing relapses. Patients And Methods Phase II single-arm trial. Eligible patients: MRI stage T3b-4/N1-2/M0 LARC, within 12cm from anal verge.Treatment LCCRT (50.4Gy + 5FU/Capecitabine). Post-LCCRT, 4 cycles avelumab (10mg/kg/q2 weeks), then resection 10-12 weeks post-LCCRT. Fresh tumor biopsy/ctDNA taken at pre-LCCRT, pre-avelumab and at surgery. Primary Endpoint pCR, reported centrally. Secondary endpoints; Imaging responses, Toxicity. Exploratory; Translational studies: immune-evaluation by multiplex immune-histochemistry and biopsy-derived tumoroids. Distant relapse-free survival and relapse sites. Results Thirty-seven patients entered: 33 received avelumab, 32 had surgery. ORR Pelvic MRI (N=33): 2 CR, 14 PR, 31 DCR.Fdg Pet 10 CMR, 18 PMR. The modified Ryan pCR (Regression score=0) 19% (N=6), Regression score=1, 16% (N=5): overall 34% (N=11) had a mPR. Tumors with greater PDL1 expression showed superior pCR/tumor regression. Tumoroid studies indicated intact cellular machinery for PDL1/HLA class-1 expression modulated by IFNg. No immune-related G3 AEs and post-operative complications were as expected. Median followup 3.1yrs: 3yr estimated TTP = 82%, DRFS = 80%, DFS = 80%. Conclusions The AveRec phase II study demonstrated avelumab post LCCRT is deliverable, tolerable, with significant imaging responses and mPR rate of 34%. Tumoral immune cell subsets/checkpoint expression predictive of pathological response. The addition of immune checkpoint inhibitors warrants further evaluation in patients with LARC.
DOI: 10.48620/89529
Authors: Michael, Michael, Wong, Rachel, Gill, Sanjeev, Strickland, Andrew H, Pavlakis, Nick, Shapiro, Jeremy D, Link, Emma, Farrell, Maria, Ngan, Samuel Y, Tie, Jeanne, Heriot, Alexander G, Goldstein, David, Mitchell, Catherine, Roth, Sara, Wilson, Kasmira, Mui, Milton, Ramsay, Robert G, Segelov, Eva
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6910995798
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