Impact of precision medicine in diverse cancers: A meta-analysis of phase II clinical trials

Maria Schwaederle, Melissa Zhao, J. Jack Lee, Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, Razelle Kurzrock

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

352 Citaten (Scopus)

Samenvatting

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 metaregression) 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 v2.7 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% v2.3%, 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.

Originele taal-2Engels
Pagina's (van-tot)3817-3825
Aantal pagina's9
TijdschriftJournal of Clinical Oncology
Volume33
Nummer van het tijdschrift32
DOI's
StatusGepubliceerd - 10 nov. 2015
Extern gepubliceerdJa

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