Abstract
BACKGROUND: Programmed cell death protein 1 (PD-1) blockade improved the survival of patients with mismatch repair deficient (dMMR) and/or microsatellite instability-high (MSI-H) tumors, leading to tumor-agnostic approval of pembrolizumab in this population. Whether anti-programmed death (ligand)-1 [PD-(L)1] agents may achieve similar efficacy in dMMR/MSI-H metastatic gastric cancer (mGC) compared to metastatic colorectal cancer (mCRC) is unclear. MATERIALS AND METHODS: We conducted a multicenter cohort study to collect data on patients with dMMR/MSI-H mGC or mCRC treated with anti-PD-(L)1 monotherapy globally at 17 tertiary cancer centers. Clinical features were balanced according to tumor type through the inverse probability of treatment weighting (IPTW) method. The primary endpoint was overall survival (OS), as evaluated from the first anti-PD-(L)1 administration. RESULTS: The cohort included 398 mCRC and 121 mGC patients, with a median follow-up of 34.6 and 25.1 months, respectively. The two populations differed for several baseline clinical features: patients with mCRC had younger age (60 versus 68 years, P < 0.001), better performance status (PS 0: 46% versus 34%, P = 0.062), higher frequency of primary tumor resection (82% versus 49%, P < 0.001) and liver metastases (38% versus 24%, P = 0.005), yet lower rates of distant nodal metastases (57% versus 83%, P < 0.001) and synchronous presentation (51% versus 76%, P < 0.001). After IPTW adjustment, patients with mGC showed no significant difference in progression-free survival (PFS) and OS compared to those with mCRC [PFS: hazard ratio (HR) 0.55, P = 0.077; OS: HR 0.65, P = 0.200]. CONCLUSIONS: Despite patients with dMMR/MSI-H mGC being enriched with poor prognostic factors as compared to the mCRC counterpart, anti-PD-(L)1 monotherapy's efficacy appears similar in the two tumor types.