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.

Cold atmospheric plasma: Novel opportunities for tumor microenvironment targeting

“…Several onco‐therapeutics of this kind have been made commercially available. For instance, pembrolizumab (PD1 antibody) was shown effective in treating many types of malignancies such as triple negative breast cancers, 66 cervical cancers, 67 prostate cancers, 68 gastric cancers, 69,70 esophageal cancers, 71 gastroesophageal junction cancers, 70 bladder cancers, 72 pancreatic cancers, 73 non‐small lung cancers, 74,75 melanomas, 75 head and neck cancers, 76 endometrial cancers, 77 colorectal cancers, 78 urothelial cancers 79 ; and was approved by the USA Food and Drug Administration (FDA) for treating tumor mutational burden‐high solid tumors, 80 microsatellite instability‐high solid tumors, 81 advanced urothelial carcinomas ineligible for cisplatin‐containing chemotherapy, 82 recurrent or metastatic head and neck squamous cell carcinomas with disease progression on or after platinum‐containing chemotherapies, 83 recurrent locally advanced or metastatic merkel cell carcinomas, 84 recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinomas expressing PD‐L1, 85 cervical cancers expressing PD‐L1, 86 BCG‐unresponsive non‐muscle invasive bladder cancers, 87 metastatic non‐small cell lung cancers expressing PD‐L1 (as a first‐line therapy), 88–90 MSI‐H/dMMR advanced unresectable or metastatic colorectal carcinomas (as a first‐line therapy), 91 metastatic melanomas (as a second‐line therapy), 92 and locally recurrent unresectable or metastatic triple negative breast cancers through combined use with chemotherapies 93 . As an example of PD‐L1 antibodies, nivolumab was shown effective for treating recurrent squamous‐cell carcinomas of the head and neck, 94,95 advanced renal‐cell carcinomas, 96 metastatic melanomas, 97 advanced squamous‐cell non‐small cell lung cancers 98 ; and was approved by FDA in the treatment of relapsed or progressive classical Hodgkin lymphomas, 99 advanced renal cell carcinomas, 100 metastatic non‐small cell lung cancers with progression on or after platinum‐based chemotherapies, 101 bladder cancers, 102 BRAF(V600) wild‐type unresectable or metastatic melanomas (as a first‐line therapy), 103 ad...…”

Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis

“…However, it is important to note that the majority of studies did not focus on first-line therapy. In a meta-analysis conducted by He Jin et al ( 28 ), pembrolizumab was compared to other treatments for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. The findings suggest that pembrolizumab is a highly effective and safe treatment for this population.…”

Immune checkpoint blockade therapy for BRAF mutant metastatic colorectal cancer: the efficacy, new strategies, and potential biomarkers

“…With economic development, there is a trend toward younger patients being diagnosed with CRC, which may be related to environmental factors, lifestyle, diet, and genetics [ 1 ]. Although screening strategies effectively reduce mortality and morbidity from CRC [ 2 ], approximately 20–35% of CRC patients have distant metastases at the time of the first diagnosis [ 3 , 4 ]. The five-year survival rate among metastatic CRC (mCRC) patients remains only 13% [ 5 ].…”