Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, MSI-high or MMR-deficient CRC

Abstract

Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.

Keywords::

• anti-PD-1 inhibitors
• biomarkers
• colorectal cancer
• immuno-oncology therapy
• microsatellite instability
• network meta-analysis
• systematic literature review

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1633

Author contributions

Conception/design: M Amonkar, R Aguiar-Ibáñez, M Chase and S Keeping. Collection and/or assembly of data: H Jin, M Thosar and S Keeping. Data analysis and interpretation: H Jin, M Amonkar, R Aguiar-Ibáñez, M Chase and S Keeping. Manuscript writing: H Jin and S Keeping. Final approval of manuscript: H Jin, M Amonkar, R Aguiar-Ibáñez, M Thosar, M Chase and S Keeping.

Financial & competing interests disclosure

This study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. H Jin, M Thosar and S Keeping are employees of PRECISIONheor LLC, which received funding from Merck & Co., Inc to conduct the study. M Amonkar and M Chase are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. R Aguiar-Ibáñez is an employee of Merck Canada Inc., Kirkland, QC, Canada. M Amonkar, M Chase and R Aguiar-Ibáñez are shareholders of Merck & Co., Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. H Jin, M Thosar and S Keeping are employees of PRECISIONheor LLC, which received funding from Merck & Co., Inc to conduct the study. M Amonkar and M Chase are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. R Aguiar-Ibáñez is an employee of Merck Canada Inc., Kirkland, QC, Canada. M Amonkar, M Chase and R Aguiar-Ibáñez are shareholders of Merck & Co., Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.