EP823 - Efficacy and Safety of Short-course Radiation Combining with Neoadjuvant Chemotherapy and PD-1Inhibitor for MSS/pMMR Locally Advanced Rectal Cancer.

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Purpose/Background: Objective
Our research aims to evaluate the efficacy and safety of immunotherapy combined with neoadjuvant chemoradiotherapy in MSS/pMMR type LARC patients .The major objective of this study is to evaluate the pathological complete response rate (pCR rate)of patients accepted radical resection ; Secondary objectives include evaluating the efficacy of neoadjuvant therapy based on CWWD criteria and assessing of overall survival. Adverse events related to neoadjuvant therapy and surgery were assessed using the CTCAE criteria (version 5.0) and the Clavien-Dindo classification system respectively.

Methods/Interventions: Patients and Therapeutic Schemes
We included 33 MSS/pMMR type locally advanced rectal cancer patients from the First Affiliated Hospital of Zhengzhou University from February 2021 to January 2023. All patients underwent at least two cycles of immunotherapy combined with short course neoadjuvant radiation (25Gy/5Fx，1week) and neoadjuvant chemotherapy. Immunotherapy uses PD-1 inhibitor camrelizumab (200mg, ivgtt,day 1), while neoadjuvant chemotherapy uses CAPOX protocol (oxaliplatin, 130mg/m2, ivgtt,day 1; capecitabine 1000mg/m2,bid,po,day1-14; one treatment cycle is three weeks). After completing radiation, wait for at least one week before undergoing immunotherapy and chemotherapy. After completing neoadjuvant therapy, take the clinical evaluation to choose radical resection or Wait&Watch strategy.

Results/Outcomes: Result
After neoadjuvant therapy, 3 patients ultimately achieved cCR, 17 patients achieved near-cCR, and 13 patients achieved non-cCR. Based on MDT(Multi-Disciplinary Treatment), 28 patients underwent radical resection, of which 16 patients achieved pCR, and the other 12 patients were TRG-1 (7 patients), TRG-2 (4 patients), and TRG-3 (1 patient), with a pCR rate of 57.1%; 5 patients took the Wait&Watch strategy. We evaluated the safety of neoadjuvant therapy, and found that the vast majority of patients (32/33) experienced one or more adverse events related to neoadjuvant therapy. Grade 1-2 adverse events included nausea (81.8%), hemoglobin reduction (75.6%), and rash (51.5%); Grade 3 adverse events include lymphocyte depletion 5 (15.2%), liver function abnormal 5 (15.2%), and no grade 4-5 adverse events occurred. We conducted a median follow-up of 30 months (12-43) for all patients, and a total of 5 patients occurred recurrence or metastasis.

Conclusion/Discussion: Conclusion
·Short-course radiation in conjunction with CAPOX and camrelizumab as a neoadjuvant therapy can effectively enhance the clinical efficacy of MSS/pMMR type LARC, achieving a pCR rate of 57.1%，which having a high level among all similar studies.
 ·This neoadjuvant therapy scheme can effectively reduce tumor size and has a clinical response rate of 60.6%. What’s more, the anal preservation rate is 90.9% among all patients.
·Based on our current follow-up results, we can predict that patients will have a good longterm outcomes with a long overall survival. This study provides new ideas and references for the treatment of MSS/pMMR type LARC, offering hope for improved outcomes and quality of life for patients facing this formidable disease.
·The combination of immunotherapy and neoadjuvant chemoradiotherapy has good safety, with no serious adverse events related to neoadjuvant therapy or surgery. It will have a wider application value in future clinic.