PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study

Abstract

PURPOSE To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti–PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti–PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti–PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti–PD-1/PD-L1 group). Propensity score–based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti–PD-1/PD-L1 and anti–PD-1/PD-L1, respectively. The chemo-anti–PD-1/PD-L1 group showed significant improvements versus the anti–PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti–PD-1/PD-L1 versus anti–PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION Chemo-anti–PD-1/PD-L1 is superior to anti–PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.