Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials

Abstract

Purpose: The impact of a personalized cancer treatment strategy (ie, matching patients with drugs based on specific biomarkers) is still a matter of debate.

Methods: We reviewed phase II single-agent studies (570 studies; 32,149 patients) published between January 1, 2010, and December 31, 2012 (PubMed search). Response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared for arms that used a personalized strategy versus those that did not.

Results: Multivariable analysis (both weighted multiple linear regression and random effects meta-regression) demonstrated that the personalized approach, compared with a nonpersonalized approach, consistently and independently correlated with higher median RR (31% v 10.5%, respectively; P < .001) and prolonged median PFS (5.9 v 2.7 months, respectively; P < .001) and OS (13.7 v 8.9 months, respectively; P < .001). Nonpersonalized targeted arms had poorer outcomes compared with either personalized targeted therapy or cytotoxics, with median RR of 4%, 30%, and 11.9%, respectively; median PFS of 2.6, 6.9, and 3.3 months, respectively (all P < .001); and median OS of 8.7, 15.9, and 9.4 months, respectively (all P < .05). Personalized arms using a genomic biomarker had higher median RR and prolonged median PFS and OS (all P ≤ .05) compared with personalized arms using a protein biomarker. A personalized strategy was associated with a lower treatment-related death rate than a nonpersonalized strategy (median, 1.5% v 2.3%, respectively; P < .001).

Conclusion: Comprehensive analysis of phase II, single-agent arms revealed that, across malignancies, a personalized strategy was an independent predictor of better outcomes and fewer toxic deaths. In addition, nonpersonalized targeted therapies were associated with significantly poorer outcomes than cytotoxic agents, which in turn were worse than personalized targeted therapy.

Fig 1.

Benefit of personalized therapy. (A) Results from the pooled and meta-analysis comparing the personalized strategy versus nonpersonalized strategy are represented for response rate (RR), progression-free survival (PFS), and overall survival (OS). All P < .001 comparing arms adopting a personalized approach versus a not personalized approach. Six hundred thirty-eight arms had values available for the RR analysis (pooled analysis and meta-analysis; 112 arms were personalized, and 526 were not). For the PFS analysis, 530 arms had values for the pooled analysis (personalized, n = 86; not personalized, n = 444), and 342 arms had median PFS values and their corresponding 95% CIs available for the meta-analysis (personalized, n = 59; not personalized, n = 283). For the OS analysis, 441 arms had values for the pooled analysis (personalized, n = 49; not personalized, n = 392), and 247 arms had median OS values and their corresponding 95% CIs available for the meta-analysis (personalized, n = 21; not personalized, n = 226). (B) Forest plots for RR, PFS, and OS (left to right). EMA, European Medicines Agency; FDA, US Food and Drug Administration.