2267 - Hypofractionated Radiotherapy Combined with Immunotherapy and Chemotherapy for Locally Recurrent Rectal Cancer (TORCH-R): A Prospective, Single-Arm, Two-Cohort, Phase II Trial

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 19

POSTER

Presenter(s)

Ruiyan Wu, MD, PhD - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai,

R. Wu¹, Y. Liu¹, L. Huang¹, F. Xia¹, L. Shen¹, H. Zhang¹, Y. Wang¹, Y. Wang¹, Z. Zhang¹, J. Wan¹, and Z. Zhang²; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Clinical Research Center for Radiation Oncology; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China

Purpose/Objective(s):

Local recurrence of rectal cancer (LRRC) remains a therapeutic challenge. This study aimed to assess the outcome of hypofractionated radiotherapy (HFRT) with PD-1 inhibitor and standard-of-care systemic therapy (SoC) in proficient mismatch repair or microsatellite stable (pMMR/MSS) patients with LRRC.

Materials/Methods:

We conducted a prospective, single-arm, two-cohort, phase 2 trial enrolling LRRC patients with or without oligometastases. Eligible patients with previously untreated (cohort A) or progressive disease after first line therapy (cohort B), were assigned received 25-40 Gy/5 Fx irradiation or 15–30 Gy/5 Fx reirradiation for pelvic recurrence, followdd by 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. The primary endpoint was confirmed local recurrence objective response rate (ORR). The study is registered with ClinicalTrials.gov, NCT05628038.

Results:

Between Jan 31, 2023, and Jan 6, 2025, a total of 92 patients were enrolled, including 53 in cohort A and 39 in cohort B. The median follow-up duration was 23.9 months (95% CI 19.4–27.4). The objective response rate (ORR) for local recurrence was 86.8% (95% CI 74.7–94.5; 46/53) in cohort A and 76.3% (95% CI 59.3–87.6; 29/38) in cohort B. Radical resection (R0) was achieved in 18 patients (34.0%, 95% CI 21.6–48.7) in cohort A and in 10 patients (26.3%, 95% CI 13.4–42.8) in cohort B. The complete response (CR) rate was 35.8% (95% CI 22.8–50.0), comprising 15 clinical CR and 4 pathological CR patients in cohort A, and 26.3% (95% CI 13.4–42.8), comprising 7 clinical CR and 3 pathological CR patients in cohort B. The 2-year progression-free survival rate was 59.0% (95% CI 45.4–76.5) in cohort A and 34.1% (95% CI 19.6–59.3) in cohort B. The most common grade 3–4 adverse events were neutropenia (6.8% in cohort A vs. 23.5% in cohort B) and diarrhea (17.1% in cohort A vs. 20.6% in cohort B). One patient died of tumor hemorrhage after initial treatment in cohort B, which was assessed as unrelated to the therapy. Thus, the case was not included in the efficacy evaluation.

Conclusion:

To our knowledge, this is the first prospective study showing the activity and safety of hypofractionated radiotherapy combined with PD-1 inhibitor plus SoC in pMMR/MSS LRRC. The combination deserves further validation in future randomised, controlled trial.