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PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal
Mifen Chen1, Zhenghang Wang1, Zimin Liu2
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
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.
Insights
Combining chemotherapy with PD-1/PD-L1 inhibitors significantly improves treatment outcomes for advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers compared to monotherapy.
Area of Science:
- Oncology
- Gastroenterology
- Immunotherapy
Background:
- Advanced gastrointestinal cancers with microsatellite instability (MSI)/mismatch repair-deficiency (dMMR) represent a distinct molecular subtype.
- The efficacy of PD-1/PD-L1 inhibitors in this population is well-established, but the role of combination therapy with chemotherapy is less clear.
Purpose of the Study:
- To compare the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus PD-1/PD-L1 inhibitor monotherapy.
- To evaluate outcomes in patients with advanced MSI/dMMR gastrointestinal cancers.
Main Methods:
- Retrospective analysis of 256 patients with MSI/dMMR gastrointestinal cancer.
- Comparison of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
- Propensity score-based overlap weighting and sensitivity analyses were used to control for confounding factors.
Main Results:
- The combination of chemotherapy and PD-1/PD-L1 inhibitors (chemo-anti-PD-1/PD-L1) demonstrated significantly higher ORR (61.8% vs 38.8%), DCR (92.6% vs 74.5%), and improved PFS and OS compared to anti-PD-1/PD-L1 monotherapy.
- Post-overlap weighting analysis confirmed these significant improvements, with ORR at 62.5% vs 38.3% and DCR at 93.8% vs 74.2%.
Conclusions:
- Combination therapy with chemotherapy and PD-1/PD-L1 inhibitors is superior to monotherapy in advanced MSI/dMMR gastrointestinal cancers.
- This combination strategy offers improved efficacy and should be considered for this patient population.
