Short course immunotherapy as curative-intent treatment in stage I-III dMMR rectal cancer.

Abstract

121 Background: Neoadjuvant chemo-radiation followed by resection is standard treatment for patients with locally advanced rectal cancer (RC). A subset of RC are mismatch repair deficient (dMMR). Check-point inhibitors (CPI) are the standard of care in dMMR colorectal cancer (CRC) in the metastatic setting, and recent trials have demonstrated impressive efficacy in early CRC, even with a limited number of cycles. In the NICHE-II trial (Chalabi et al, ESMO 2022) 72 of 107 patients (67%) with colon cancer obtained pathological complete response (pCR) after short course CPI. In patients with RC, Cercek et al (NEJM 2022) showed that 12 patients (100%) obtained pCR after 6 months of dostarlimab. The efficacy of CPI in dMMR RC has only been evaluated in few studies. Here we report data from a Danish trial with early dMMR RC. EU CT number 2022-500646-14-00. Methods: The purpose was to evaluate the efficacy and tolerability of 1 cycle of nivolumab (3 mg/kg days 1 and 15 - nivo) and ipilimumab (1 mg/kg day 1 - ipi) in patients with early stage dMMR RC. The primary endpoint was number of patients with clinical complete response (cCR - no visible or palpable tumor) evaluated 4 weeks after nivo-ipi. Patients achieving a clinical, radiological, pathological (representative biopsy without viable tumor cells), and molecular complete response was offered a thorough watchful waiting strategy without surgery. Results: 5 patients were treated, 4 patients received a single cycle of nivo-ipi and 1 patient received 2 cycles of nivo-ipi, as the tumor was still visible at the first endoscopy (Table). All 5 patients were evaluated 4 weeks after completing nivo-ipi and all 5 patients (100%) achieved cCR. All 5 patients were ctDNA positive (Jensen et al, Clin Chem 2020) at diagnosis, 4 patients turned negative after therapy (1 pending). No patient needed radiotherapy and all patients agreed to non-surgical watchful waiting. No patient has had progression or recurrence (1-42 months follow-up). Conclusions: Short-course nivo-ipi is very effective in locally advanced dMMR rectal cancer and may become an alternative to resection. Clinical trial information: 2022-500646-14-00 . [Table: see text]