KEY TAKEAWAYS
- The phase II trial aimed to test the hypothesis that avelumab, given post-LCCRT, can enhance pathological/imaging response rates and reduce local/distant relapse rates in resectable LARC pts.
- The primary endpoint is to determine pCR. Secondary endpoints include MRI and FDG PET/CT imaging response based on RECIST1.1 and PERCIST criteria.
- The study found that avelumab after LCCRT for LARC was well-tolerated and showed promising activity.
Neoadjuvant long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) has a 10-30% complete pathological response (pCR) rate but 20-40% non-response and 10-15% local recurrence. Radiotherapy (RT) is immunostimulatory but also immunosuppressive by PDL1 and MDSC.
Researchers aimed to test the hypothesis that avelumab, given post-LCCRT, can enhance pathological/imaging response rates and reduce local/distant relapse rates in resectable LARC pts.
The study included LARC pts and gave them the standard LCCRT treatment followed by 4 cycles of Avelumab (AV) before surgery. Biopsies and ctDNA samples were collected at different time points. Inclusion criteria included LARC, planned LCCRT, measurable disease, good health, and no AV contraindications. The primary endpoint was the complete pCR rate post-LCCRT (≥35%). Secondary endpoints include imaging responses by RECIST1.1 and PERCIST and toxicity assessment. Exploratory endpoints were tumoural immune cell subsets/checkpoint expression (by multiplex immunohistochemistry and in-vitro functional assays) and ctDNA analysis, distant relapse-free survival, and the sites of relapse.
Of 37 pts across 6 sites, 33 (89%) received the planned treatments for LCCRT, AV, and surgery when possible. Their median age was 55 years (range: 31-76), with a gender distribution of 23 males and 10 females. Baseline tumor stages were T3b-d in 75% and T4a-b in 25%. None had dMMR/MSI-H tumors. Overall, 33 pts completed LCCRT, 31 (83%) completed all 4 AV cycles, and 32 (86%) had planned surgery (22 ULAR, 2 APR, 2 AR, 6 Other). Pelvic MRI results before surgery (N=33) 2 CR, 14 PR, and 31 DCR. FDG PET/CT findings (N=31) 10 CMR, 18 PMR, and 3 SMD. About 10 pts experienced Grade 3/4 adverse events (AEs), totaling 15 G3/4 events, with only 3 related to treatment and none reaching G4 severity. No specific immune-related G3 AEs were observed. Post-operative complications were as expected.
The study found Avelumab after LCCRT for LARC was well-tolerated and showed promising activity. Pathological response, biological substudies, and survival data will be reported.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3616
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03299660
Michael Michael, Rachel Wong, Sanjeev Singh Gill, Andrew H. Strickland, Nick Pavlakis, Jeremy David Shapiro, Emma Link, Maria Farrell, Samuel Y Ngan, Alexander Graham Heriot, David Goldstein, Catherine Mitchell, Kasmira Wilson, Milton Mui, Robert George Ramsay, and Eva Segelov. DOI: 10.1200/JCO.2023.41.16_suppl.3616 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 3616-3616.
