Rectal arterial infusion chemotherapy combined with anti-PD1 antibody for microsatellite stable locally advanced rectal cancer: The effectiveness and safety of a single-arm, phase II study.

e15660 Background: The standard neoadjuvant therapy for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). Nevertheless, nCRT is linked to an increased risk of peri-operative complications. Neoadjuvant chemotherapy alone demonstrates an objective response rate of approximately 60% and a lower pathological complete response (pCR) rate compared to nCRT.Against this backdrop, we put forward a novel therapeutic strategy, which encompasses arterial infusion chemotherapy and intravenous anti-PD1 antibody, after induction chemotherapy.The objective of this study is to achieve a high pCR rate in patients with microsatellite-stable (MSS) LARC. Methods: Eligible patients with LARC (tumor located 5 - 12 cm from the anal verge, T3/4a or TanyN+) were administered two cycles of CAPOX. Patients who achieved a regression of more than 20% in the maximum tumor diameter received two cycles of rectal arterial infusion chemotherapy with oxaliplatin (50mg, Day 1), intravenous anti-PD1 inhibitor (200mg, Day 2), and capecitabine (1000mg/m2, orally, twice daily, Day 1-14). Total mesorectal excision (TME) was to be performed within six weeks after the last chemotherapy session. Patients with a tumor regression of less than 20% were recommended to receive nCRT. The primary endpoint was pCR rate. A total of 38 patients are planned to be enrolled to receive the arterial infusion chemotherapy combined with intravenous anti-PD1 antibody. Results: Sixty-one patients were enrolled in the study. After induction chemotherapy, 36 out of 61 patients met the 20% regression criterion. One of these 36 patients declined further treatment and withdrew from the study. Subsequently, 35 patients underwent arterial infusion chemotherapy combined with intravenous anti-PD1 antibody.Among them, one patient was deemed to have achieved a clinical complete response and refused operation. Three patients are awaiting surgery and 31 patients had undergone TME operations. The pCR rate was 35.5% (11/31). According to the tumor regression grading（TRG） standard of AJCC, the number of patients in TRG 0, 1, 2, and 3 was 11, 9, 11, and 0, respectively. The rate of major pathological response (MPR) is 77.4% (24/31). Among patients who completed the study protocol, 74.2% (23 of 31) had MRI suspected positive lymph nodes. However, the postoperative pathological results indicated that only 1 lymph node of 1 patient was positive and the remaining 30 patients were diagnosed as pN0. In terms of safety, 8 out of 31 patients had grade 3 adverse event. Conclusions: For MSS LARC patients, rectal arterial infusion chemotherapy of oxaliplatin combined with intravenous anti-PD1 antibody achieved a high pCR rate, demonstrated a favorable therapeutic effect on lymph node metastasis, and exhibited good safety. Clinical trial information: NCT05307198 .