Regorafenib and nivolumab in refractory microsatellite stable, metastatic colorectal cancer and impact of site of dominant disease.

Abstract

e15594 Background: Several studies have explored the role of Regorafenib and Nivolumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). 1,2,3,4 Notably ORR in the mCRC patients in RegNivo trial was associated with higher incidence of lung metastases. 1 The initial objective response rate of 33% seen in the RegoNivo trial was not replicated in the subsequent trials but absence of liver metastases was associated with more favorable response. 4 Methods: We evaluated the outcome of patients with MSS mCRC treated on compassionate basis with Regorafenib 80mg/day for 21 days q28 day cycle and Nivolumab 240mg q14 days or 480mg q28 days in the community academic setting and correlated with next generation sequencing and site of disease. Results: A total of 9 patients were treated between April 2020 and June 2024 with Rego/Nivo. All patients had MSS mCRC and had progressed on 5FU, oxaliplatin, irinotecan, bevacizumab, EGFR inhibitor if appropriate. No patients had Her2 amplification. 5 patients had KRAS mutation and others had KRAS/NRAS/BRAF wild type. Overall response rate was 2/9 (22%), 2 with stable disease (22%) and 5 with progressive disease. Both responders had lung dominant disease at time of treatment with this regimen. One patient experienced a durable complete response (CR), currently 4 years off treatment with no evidence of recurrence at time of submission. Second patient had partial response (PR) with progression after 7.5 months. Both patients had normalization of CEA on therapy. No grade 3 or above treatment related adverse events were noted. Conclusions: Regorafenib and Nivolumab were well tolerated in later line settings in mCRC. There was 1 durable CR off all treatment and 1 PR noted in patients with lung dominant disease. Given evidence of exceptional response after exhausting standard therapies, further investigation in patients with lung dominant disease is warranted. [1] Fukuoka et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). [2] Wang et al. Regorafenib and Nivolumab or Pembrolizumab Combination and Circulating Tumor DNA Response Assessment in Refractory Microsatellite Stable Colorectal Cancer. Oncologist 2020 May 30;25(8):e1188–e1194. [3] Kim et al. A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer. European Journal of Cancer. Volume 169, July 2022, Pages 93-102. [4] Fakih et al. Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC) Journal of Clinical Oncology. Volume 39, Number 15_suppl.