Real-world outcomes for dMMR/MSI-H colorectal cancer: Navigating rapidly evolving oncologic practices in a community hospital.

Abstract

e15519 Background: The incidence of Deficient Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Colorectal Cancer (CRC) is 15% among all CRCs. Treatment with immune checkpoint inhibitors (ICI) has transformed the field of CRC. The KeyNote177 trial demonstrated Pembrolizumab led to significantly longer progression-free survival than chemotherapy for MSI-H CRC. The CheckMate-142 study showed Nivolumab with low-dose Ipilimumab had a robust, durable, and well-tolerated clinical response as first-line therapy for MSI-H CRC. We present real-world data on treatment outcomes with different modalities for MSI-H CRC in a community hospital. Methods: The cases were identified from our institution’s electronic medical record. Our inclusion criteria included patients older than 18 years old, diagnosed with locally advanced or metastatic CRC based on TNM staging, histopathologic diagnosis of MSI-H, and receiving treatment at our institute with either surgery(S), chemotherapy(C), immunotherapy(I), or a combination of therapies. The study protocol was reviewed and approved by the institute's IRB. Results: We conducted a retrospective analysis of 11 patients (ranging from 31 to 80 years old). Of the 11 cases, 6 were metastatic and 5 were locally advanced. Of the 6 metastatic cases, 3 SCI cases reached complete remission (CR). Of the 2 SI cases, one had stable disease, and the other, receiving palliative treatment, died. The 1 CI case passed from complications unrelated to the CRC. Of the 5 locally advanced cases, 2 SCI cases reached partial remission (PR), 1 SI case reached CR, and 1 SC case reached CR. The most common treatment-associated side effects were cold sensitivity, fatigue, hypothyroidism, and neuropathy; no patients died from treatment-related complications. Within our small, isolated sample, the overall response rate (ORR) was 72.7%, and the disease control rate was (DCR) 81.8% with 6 CR and 2 PR. Conclusions: NCCN guidelines recommend the use of checkpoint inhibitors as first-line therapy or as a non-first-line treatment if another agent was initially used in MSI-H CRC. Our practice adhered to the standard of care in 81.8% of these cases. This case series shows remarkable response to the combination of S, C, and I, especially in metastatic cases where all 3 cases treated with SCI achieved CR. Isolating response rates in similar populations to determine future treatment plans and reaching for ICIs sooner can further improve our practices and outcomes. In prior studies, when treated with ICI, one-third of patients have shown primary resistance or early disease progression. One case in our series achieved CR through the use of CI together instead of in succession based on initial response. This case highlights the need for further exploration of the combination of Pembrolizumab and chemotherapy (FOLFOX) to treat locally advanced MSI-H CRC.