Real-world experience of immune checkpoint inhibitors in MSI-H/dMMR metastatic colorectal cancer in a tertiary cancer center in Saudi Arabia

According to Globocan analysis, colorectal cancer (CRC) is the second most diagnosed cancer in Saudi Arabia, with an estimated 4,007 new cases projected in 2020. Therefore, CRC poses a significant burden on the Saudi community and the healthcare system. Here, we described a real-world experience of immune checkpoint inhibitors in MSI-H/dMMR metastatic colorectal cancer in a Saudi tertiary cancer center. This is a retrospective cohort study where clinicopathologic data were collected from patients with MSI-H/dMMR metastatic colorectal cancer treated with at least one of the immune checkpoint inhibitors pembrolizumab, nivolumab and/or ipilimumab at the Ministry of National Guard – Health Affairs (MNG–HA) in Riyadh between 01 June 2017 to 31 May 2022. To compare the characteristics of patients who had immune complete response (iCR) and patients who had immune progressive disease (iPD) according to iRECIST disease assessment criteria, independent t-test and Mann-Whitney U test were used for continuous variables, and Chi square and Fishers Exact test used for categorical variables. A total of 18 MSI-H/dMMR metastatic colorectal cancer patients were treated with immune checkpoint inhibitors, including 13 with pembrolizumab monotherapy, 3 with nivolumab monotherapy, 1 with nivolumab and ipilimumab, and 1 with pembrolizumab followed by nivolumab. With the median follow-up duration of 33.5 months (range 4–63 months), 10 patients had iCR and 8 patients had iPD, giving an objective response rate (ORR) of 56%. In addition, our data showed a positive association between the development of Immune-Related Adverse Events (irAEs) and response to immune checkpoint inhibitors (p-value=0.025). Out of the 10 complete responders, 7 patients (70%) had irAEs (4 thyroiditis, 2 colitis, and 1 thyroiditis and rash), whereas only one patient (12.5%) of the iPD group had thyroiditis. On the other hand, there was a negative association between the presence of peritoneal metastasis at immunotherapy initiation and response to immune checkpoint inhibitors (p-value=0.036). While half of the patients with iCR (50%) had peritoneal metastasis at immunotherapy initiation, all patients (100%) from the iPD group had peritoneal metastasis at that time point. Also, our data suggests that patients with KRAS mutation are more likely to benefit from immune checkpoint inhibitors (p-value=0.036). However, this observation is limited by the fact that KRAS mutation was not tested for 3 patients with iCR. This retrospective study provided some positive insights into the national cancer healthcare system and immunotherapy efficacy in Saudi Arabia with an impressive 56% of patients achieving iCR. Additionally, the incidence of irAEs, the metastatic site at immunotherapy initiation, and the status of KRAS mutation are likely important predictive biomarkers for response to immune checkpoint inhibitors within MSI-H/dMMR metastatic colorectal cancer. These observations are being validated at a multi-center study that we are conducting.