Retrospective cohort of total neoadjuvant therapy (TNT) in high-risk locally advanced rectal cancer (HR-LARC): Additional sintilimab (PD-1) in tri-modality approach.

Abstract

e15604 Background: TNT is an emerging practice adapted to ensure all patients (pts) receive of systemic therapy, particularly for pts with high risk recurrence. Our previous phase II trial of TNT in MRI stratified HR-LARC demonstrated high down-staging rate and improved complete response with acceptable toxicity (manuscript under review). The aim of this retrospective cohort study was to evaluate the feasibility of sintilimab in combination with chemotherapy in TNT tri-modality treatment of pts with HR-LARC. Methods: HR-LARC pts who were given 3 cycles of sintilimab (200mg, iv, q3w) in combination with CapeOx followed by sequential long-course radiotherapy (IMRT GTV50.6 Gy/CTV 41.8 Gy/22f), 2 cycles CapeOx and surgery were enrolled from Beijing Cancer Hospital, CHN. The high risk was defined as middle to low RC (≤8cm to ARJ or 12 cm per sigmoidoscopy) with ≥1 factor from MRI features: clinical stage T3c/d-T4a/b, or N2 or MRF (+) or EMVI (+). The clinical outcomes included pathological response, major response rate (cCR+MPR), R0 resection rate, and toxicity. Results: From Feb 2019 to Oct 2020, 19 cases were identified with median distal location 4 cm (3-7), T2/T3/T4 1/15/3, N1/N2a/N2b 7/4/8, MRF+ 8/11, EMVI+ 8/11. Other characteristics were pMMR/MSS 100%, age 67y (47-78), male 57.9%, PS 1 100%, c-stage III 100% (18), median diameter of primary lesion 5.1 cm (2.1-7.5). As of 30th Dec 2020, 84.2% (16/19) received neoadjuvant therapy and completed surgical resection, with R0 resection rate 100%. One pts denied surgery and two chose watch & wait since achieving cCR 10.5% (2/19). Of 16 resection pts, 13 had sphincter-sparing surgery (LAR or TaTME). One had Hartmann procedure, and two had abdominal perineal resection. The sphincter preservation rate was 84.2% (16/19). The pCR was 26.3% (5/19), and MPR was 47.3% (9/13). The major response rate was 57.9% (11/19), 4/2/13 of which completed intact TNT schema, induction and RT, and induction phase only, respectively. Treatment related adverse events (TRAE) occurred in 6 pts (31.6%) in grade (gr) 1-2 (CTCAE 5.0) without any gr 3-5 events occurred. Immune-related AEs were found in 2 pts with hypothyroidism (gr 1,2). Postoperative complications included two gr2 (Clavien-Dindo) events of anastomtic bleeding and infection. Of note, 3 pts with anastomotic stenosis got stoma reversion after dilation. Conclusions: Given the impressive response rate (57.9%), this retrospective analysis suggested a potential enhanced anti-cancer activity and good tolerability in pMMR/MSS HR-LARC from sintilimab in combination with TNT. The encouraging results warrant further evaluation of this approach in prospective trial.