Personalized Medicine Delivers Better Outcomes: More Proof

Roxanne Nelson, BSN, RN

May 19, 2016

A large meta-analysis of phase 1 clinical trials found that patients for whom a personalized, biomarker-based selection strategy was used had significantly better outcomes than patients for whom a biomarker-based approach was not used.

The meta-analysis included 346 published phase 1 trials (351 arms) that included 13,203 patients. It found that a personalized strategy was an independent predictor of improved response rates and progression-free survival.

"A biomarker-based approach, which is the foundation of precision medicine, was an independent predictor of improved outcomes even in a phase 1 refractory cancer population," said lead study author Maria Schwaederle, PharmD, of the Center for Personalized Cancer Therapy, University of California, San Diego, School of Medicine.

"Targeted drugs that were developed without a biomarker performed poorly, with a median response rate of only 5%," explained Dr Schwaederle, who presented the data during a press briefing held in advance of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. "But a biomarker-based approach to phase 1 drug development results in high response rates, with median response rates over 40% when genomic biomarkers are used."

Historically, phase 1 trials have examined toxicity only, but this meta-analysis has shown this to be outdated.

"High efficacy levels can be achieved in phase 1 trials with the use of biomarker selection," she pointed out.

Biomarkers an Effective Strategy

The current study is the third in a series of studies by the same authors, two of which have already been published.

The first was a meta-analysis of phase 3 trials of targeted agents; the second was a meta-analysis of phase 2 trials of targeted agents.

According to study coauthor Richard Schilsky, MD, ASCO chief medical officer and former chief of the Section of Hematology-Oncology (2009-2012) at the University of Chicago, all three studies are "basically showing that if you use a biomarker to identify a patient to receive a targeted therapy, then that's associated with better outcomes than if you don't use a biomarker and you treat an unselected patient population."

The current study is the first to demonstrate that these benefits are apparent even at an early stage of clinical development, suggesting that tumor biomarkers should be increasingly used to select patients for phase 1 clinical trials, he said.

"The point of all this is to continue to develop the evidence base suggesting that matching drugs to biomarkers is an effective strategy in the whole realm of precision medicine for cancer," Dr Schilsky told Medscape Medical News.

Precision Medicine Is Here

Dr Schwaederle and colleagues examined efficacy and safety data from 346 phase 1 trials published between 2011 and 2013 (58 used employed precision medicine, and 293 did not).

Their analysis compared response rates (n = 351 arms; 13,203 patients), progression-free survival (PFS) (n = 45 arms; 1700 patients), and toxic death rate (n = 351 arms, 13,203 patients) between the two arms.

Overall survival was not included because data for overall survival were only included in 27 studies (four of which were personalized).

The personalized strategy independently correlated with improved response rates (30.6% vs 4.9%, P < .0001) and a prolonged median PFS (5.7 vs 2.95 months, P = .0002).

In the majority of personalized strategy arms (98.3%), targeted agents were used, but most of the arms in which targeted agents were used followed a nonpersonalized approach, and patients were not selected on the basis of a cognate biomarker (76%).

The authors conducted a subanalysis within targeted arms (n = 234 arms) that showed improved response rates when using a biomarker-based approach, as compared with not using one (31.1% vs 5.1%, P < .0001).

In the arms using a nonpersonalized strategy, outcomes were comparable with those that tested a cytotoxic agent: median response rate, 5.1% vs 4.7% (P = 0.63); median PFS, 3.3 vs 2.5 months (P = 0.22).

The personalized arms that employed a DNA biomarker achieved higher response rates compared with those using a protein biomarker (42% vs 22.4%, P = .001).

Median treatment-related mortality did not differ statistically between arms that employed a personalized strategy in comparison with those that did not (1.89% vs 2.27%, P = 0.31).

One of the strengths of this study was that it was a comprehensive analysis of all types of trials. In addition, it looked at the use of precision medicine for a wide range of indications, commented said Don S. Dizon, MD, FACP, ASCO spokesperson and moderator of the presscast.

"This is an important study that had a very large dataset analysis of over 13,000 patients in phase 1 trials," he said. "Precision medicine is not the future of cancer care, it is the present.

"The study shows that precision medicine is here, and we can use patient selection and do much better than we have in the past," said Dr Dizon.

No research funding has been reported. Dr Schwaederle has disclosed no relevant financial relationships. Several of the study authors have relationships with industry, as noted in the abstract. Dr Dizon has financial relationships with UptoDate and Aeterna Zentaris.

2016 American Society of Clinical Oncology Annual Meeting: Abstract 11520, to be presented June 6, 2016.

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