e15523 Background: The integration of immunotherapy with chemotherapy in locally advanced rectal cancer (LARC) is a standard of care of late and needs predictive biomarkers. We investigated the relationship between tumor PD-L1 expression, metabolic imaging response, circulating biomarkers, and clinical outcomes in LARC patients receiving neoadjuvant chemo-immunotherapy. Methods: Twenty-four patients with T3–T4, N1–N3 rectal adenocarcinoma received six cycles of modified FOLFOX6 plus pembrolizumab (200 mg IV q3w). PD-L1 combined positive score (CPS) was assessed by immunohistochemistry. 18F-FDG PET-CT was performed at baseline and week 9 to quantify percentage SUV reduction. Serial plasma cell-free DNA (cfDNA) and circulating tumor cell (CTC) counts were measured. Morphologic response was evaluated per i RECIST v1.1. Correlations between biomarkers and Pathological CR rates (pCR) were analyzed using Pearson correlation coefficients. Results: Complete response (CR) was achieved in 8 patients (33%), all with CPS >50%; 14 patients (58%) achieved partial response, and 2 (9%) had stable disease. PD-L1 CPS demonstrated the strongest correlation with pCR (r = 0.94, p < 0.001), followed by SUV reduction (r = 0.93, p < 0.001), cfDNA decline (r = 0.87, p < 0.001), and CTC reduction (r = 0.86, p < 0.001). The regimen was well tolerated: Grade 1–2 toxicities included fatigue (42%), nausea (29%), and transaminitis (17%); Grade 3 events were limited to neutropenia (8%) and immune-mediated thyroiditis (4%). No Grade 4–5 toxicities occurred. Conclusions: In LARC treated with neoadjuvant FOLFOX plus pembrolizumab, PD-L1 CPS strongly predicts treatment response (radiological) and pCR. Metabolic imaging and liquid biopsy biomarkers provide complementary predictive value. This multimodal biomarker approach may enable response-adapted therapeutic strategies in rectal cancer chemo-immunotherapy. The favorable safety profile supports further investigation in larger prospective trials. Demographics. Total Participants 24 patients Age (years) Mean: 50.3 (40-60) Sex Male: 12: Female: 12 T Stage T3: 15 (62.5%), T4: 9 (37.5%) N Stage N1: 12 (50%), N2: 8 (33.3%), N3: 4 (16.7%) RECIST Response PR: 14 (58.3%), CR: 8 (33.3%), SD: 2 (8.3%)
Attili et al. (Thu,) studied this question.