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Published on: February 5, 2020
Effects of Clinicopathological Characteristics on the Survival of Patients Treated with PD-1/PD-L1 Inhibitor
Yuhan Wei1, Yongfu Li1,2, Qi Du1
1Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Background:
PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer.
Methods:
A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed.
Results:
Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 (P < 0.001) and 0.64 (P < 0.001), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54), and the difference was statistically significant (interaction, P = 0.005). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001) compared with male (HR, 0.73; P < 0.001; interaction, P = 0.004). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001) than smokers (HR, 0.63; P = 0.001; interaction, P = 0.02). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy.
Conclusions:
Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.
Insights
Programmed cell death protein 1 (PD-1)/PD-L1 inhibitors significantly improve overall survival in advanced cancers. Patient characteristics like EGFR status, sex, and smoking status predict treatment benefits, guiding personalized immunotherapy strategies.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Programmed cell death protein 1 (PD-1)/PD-L1 inhibitors represent a significant advancement in cancer treatment.
- These immunotherapies harness the patient's immune system to combat malignancies.
Purpose of the Study:
- To evaluate the efficacy of PD-1/PD-L1 inhibitor monotherapy and combination therapy in cancer treatment.
- To identify patient subgroups that benefit most from these immunotherapies based on clinical and molecular characteristics.
Main Methods:
- A systematic review and meta-analysis of randomized controlled trials comparing PD-1/PD-L1 inhibitors with non-immunotherapy treatments.
- Analysis of hazard ratios (HRs) for overall survival (OS) stratified by patient factors including sex, age, ECOG performance status, smoking history, liver metastasis, PD-L1 expression, EGFR, and KRAS status.
Main Results:
- Both monotherapy (HR 0.74) and combination therapy (HR 0.64) significantly improved OS.
- EGFR wild-type status predicted benefit from monotherapy (HR 0.77), while mutant type showed no benefit (HR 1.11).
- Combination therapy showed greater benefit in females (HR 0.45) and nonsmokers (HR 0.29) compared to males and smokers, respectively.
Conclusions:
- PD-1/PD-L1 inhibitors, both as monotherapy and in combination, substantially prolong OS in advanced cancers.
- EGFR status is a key predictor for monotherapy efficacy.
- Patient sex and smoking status are significant predictors for the effectiveness of combination immunotherapy.
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