A novel intermediate endpoint could be a useful measure in clinical trials for metastatic non-small cell lung cancer (mNSCLC), according to a recent study published in JAMA (published online June 15, 2017; doi:10.1001/jamaoncol.2017.1029).
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Within the past decade, the US Food and Drug Administration (FDA) has approved many new targeted therapies and immunotherapies to treat patients with mNSCLC. Despite the progress and robust development of these new drugs, additional intermediate end points may be needed to identify signals of early activity, prioritize combinations, and examine initial study results. One such proposed intermediate end point—milestone rates—look at survival at a given time point.
Gideon M Blumenthal, MD, Center for Drug Evaluation and Research, FDA, and colleagues conducted a study to assess the proposed milestone rates as endpoints for mNSCLC immunotherapy trials. Researchers used 14 trials from 2003 to 2013 submitted to the FDA with more than 150 patients and in which the intention-to-treat population was assessed and identified. An additional 11 randomized trials were also included from 2014 to 2016.
Researchers extrapolated data to compare trial-level milestone ratios (overall response rates [ORR] within 6 months, 9-month progression-free survival [PFS], 9-month overall survival [OS], and 12-month OS) with conventional endpoints.
Resulting analysis of milestone rates indicated a moderate association between OS milestones at 12 or 9 months and OS hazard ratio. However, no association was found between 9-month PFS or 6-month ORR and OS hazard ratio.
Although OS at 12 months had the strongest association with OS hazard ratio, researchers assert that 12 months may not be the optimal time for future trials due to increasing immunotherapy use as the control, increasing deployment of new biomarker-enrichment strategies, and increasing likelihood that patients enrolled will have longer survival. Further research is needed to determine the optimal endpoint time for such trials.
Nonetheless, “Milestone rates may be useful as a complementary tool to summarize or interpret trial results or as a secondary end point in exploratory studies,” researchers concluded.—Zachary Bessette
