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Published on: September 25, 2018
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated
Koichi Ando1,2, Ryo Manabe1, Yasunari Kishino1
1Division of Respiratory Medicine and Allergology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Abstract:
Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.
Insights
For extensive-stage small cell lung cancer, immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) showed similar overall survival to platinum-irinotecan (IP) but more adverse events. No significant differences were found between different ICIs+EP regimens.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Extensive-stage small cell lung cancer (ES-SCLC) treatment remains challenging.
- Direct comparisons of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) versus platinum-irinotecan (IP) or among different ICIs+EP regimens are lacking for previously untreated ES-SCLC.
Purpose of the Study:
- To compare the efficacy and safety of ICIs+EP versus IP.
- To compare the efficacy and safety among different ICIs+EP regimens in previously untreated ES-SCLC.
Main Methods:
- Bayesian network meta-analysis.
- Comparison of six treatment arms: pembrolizumab+EP, durvalumab+EP, atezolizumab+EP, platinum-amrubicin (AP), IP, and EP.
- Evaluation of overall survival and adverse events, including grade 3 or higher adverse events (G3-AEs), neutropenia, thrombocytopenia, and diarrhea.
Main Results:
- No significant differences in overall survival were observed between ICIs+EP and IP, or among the three ICIs+EP regimens.
- The incidence of G3-AEs was significantly higher in ICIs+EP compared to IP.
- ICIs+EP showed significantly higher rates of G3 neutropenia and thrombocytopenia but lower rates of G3 diarrhea compared to IP.
Conclusions:
- Current evidence suggests comparable overall survival for ICIs+EP and IP in ES-SCLC.
- Clinicians should consider the increased risk of certain adverse events with ICIs+EP when selecting treatment strategies.
- Further research may be needed to optimize the use of ICIs+EP and manage associated toxicities.
