67MO - Node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab in patients with MSS/pMMR locally advanced rectal cancer: A multicentre phase II trial (mRCAT)

Background

Almost 90% of rectal cancers are microsatellite stable (MSS) or mismatch repair proficient (pMMR) subtypes for which PD-1 blockade is ineffective. The effectiveness is still limited although the radiation can enhance the responses of MSS/pMMR rectal cancer to PD-1 blockade. Our study aims to investigate whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be more effective in patients with MSS/pMMR Locally advanced rectal cancer (LARC).

Methods

We conducted a open-label, prospective, multicentre, phase II trial using Simon's two-stage design. Eligible MSS/pMMR LARC patients(cT_3-4N_0/+M₀/cT₂N₊M₀) were received node-sparing modified short-course radiotherapy (the irradiated planned target volume included only the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by 4 cycles of CAPOX and tislelizumab. Total mesorectal excision (TME) will be performed at weeks 14-15. The primary endpoint is the rate of pathological complete response (pCR), with a hypothesis of an increased pCR of 30% compared with historical data of 10% after conventional CRT.

Results

Between Aug 18, 2023 to Apr 20, 2024, a total of 46 patients were screened for eligibility. 33 patients ultimately proceeded to surgery, all achieved R0 resection. pCR (TRG 0) and MPR (TRG0+1) were achieved in 78.8% (26/33) and 90.9% (30/33) patients, respectively.3 (9.1%) patients reached TRG 2, no patients had TRG 3. Treatment-related adverse events (TRAEs) of any grade occurred in 29/34 (85.3%) patients. The most common TRAEs of grade 1 or 2 included proctitis (17/34, 50%), leukopenia (14/34, 41.2%), thrombocytopenia (11/34, 32.4%) and anemia (8/34, 23.5%). Grade 3 TRAEs occurred in 5.9% (2/34) of patients, and Grade 4 TRAEs occurred in 8.8% (3/34) of patients. No grade 5 adverse events and treatment-related deaths were recorded.

Conclusions

The node-sparing radiation combined with chemo-immunotherapy regimens dramatically increased pCR rates in MSS/pMMR LARC with tolerable toxicity, which is a promising modality for the treatment of MSS/pMMR LARC patients.

Clinical trial identification

NCT05972655. Release date: August 2, 2023.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.