Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis.
Importance The impact of a biomarker-based (personalized) cancer treatment strategy in the setting of phase 1 clinical trials was analyzed. Objective To compare patient outcomes in phase 1 studies that used a biomarker selection strategy with those that did not. Data Sources PubMed search of phase 1 cancer drug trials (January 1, 2011, through December 31, 2013). Study Selection Studies included trials that evaluated single agents, and reported efficacy end points (at least response rate [RR]). Data Extraction and Synthesis Data were extracted independently by 2 investigators. Main Outcomes and Measures Response rate and progression-free survival (PFS) were compared for arms that used a personalized strategy (biomarker selection) vs those that did not. Overall survival was not analyzed owing to insufficient data. Results A total of 346 studies published in the designated 3-year time period were included in the analysis. Multivariable analysis (meta-regression and weighted multiple regression models) demonstrated that the personalized approach independently correlated with a significantly higher median RR (30.6% [95% CI, 25.0%-36.9%] vs 4.9% [95% CI, 4.2%-5.7%]; P P P P = .63; respectively; median PFS, 3.3 [95% CI, 2.6-4.0] months vs 2.5 [95% CI, 2.0-3.7] months; P = .22). Personalized arms using a “genomic (DNA) biomarker” had higher median RR than those using a “protein biomarker” (42.0% [95% CI, 33.7%-50.9%] vs 22.4% [95% CI, 15.6%-30.9%]; P = .001). The median treatment-related mortality was not statistically different for arms that used a personalized strategy vs not (1.89% [95% CI, 1.36%-2.61%] vs 2.27% [95% CI, 1.97%-2.62%]; P = .31). Conclusions and Relevance In this meta-analysis, most phase 1 trials of targeted agents did not use a biomarker-based selection strategy. However, use of a biomarker-based approach was associated with significantly improved outcomes (RR and PFS). Response rates were significantly higher with genomic vs protein biomarkers. Studies that used targeted agents without a biomarker had negligible response rates.