Neoadjuvant PD-1 blockade combined with chemotherapy followed by concurrent immunoradiotherapy for locally advanced anal canal squamous carcinoma patients: Antitumor efficacy, safety and biomarker

e15500 Background: Efficacy and safety of PD-1 inhibitors have been approved for the treatment of metastatic anal squamous cancer patients, but the efficacy of neoadjuvant treatment with PD-1 in anal squamous cancer patients has not yet been defined. We report results for the cohort of patients with locally advanced anal canal squamous carcinoma treated with neoadjuvant PD-1 inhibitor toripalimab and chemotherapy followed by concurrent immunoradiotherapy. Methods: Five locally advanced anal canal squamous carcinoma patients received 4 cycles of neoadjuvant PD-1 inhibitor toripalimab and Docetaxol and Cisplatin chemotherapy followed by concurrent immunoradiotherapy. Whole exome sequencing (WES) and mIHC were performed with the pretreatment tumor tissue for biomarker analysis. Results: Complete clinical response (cCR) was achieved in 4 patients after neoadjuvant treatment before radiotherapy while the other patient achieved near cCR. cCR was achieved in all the 5 patients 3 months after definitive immunoradiotherapy. Grade 3 toxicity was noted in 1 patient. Molecular testing revealed that PD-L1 expression (≥1%) in tumor and CD4/CD163 expression in tumor and paracancerous tissue were positively correlated with tumor shrinkage in the neoadjuvant treatment phase while TMB didn’t appear to significantly impact the response. Conclusions: PD-1 inhibitor combined with chemoradiotherapy has quite promising effect in locally advanced anal canal squamous carcinoma patients, with very mild toxicity. Pretreatment PD-L1 expression is positively correlated with tumor response to PD-1 inhibitor toripalimab and chemotherapy. It is worthy of further investigation in prospective clinical trial.