Rates at Some Milestones May Indicate Clinical Trial Results for Immunotherapeutics
A moderate association may exist between some clinical trial milestones.
An analysis of milestones in clinical trials of immune checkpoint inhibitors, targeted therapy, and conventional therapy for metastatic non-small cell lung cancer (mNSCLC) submitted to the US Food and Drug Administration (FDA) suggests a moderate association between some milestones, such as overall survival (OS) at 12 months and OS hazard ratio (HR), for immunotherapeutics.
The researchers wanted to elucidate whether novel intermediate end points (ie, milestone rate) might be useful in detecting early activity to prioritize new therapies for mNSCLC.
For this analysis, the researchers assessed data from trials submitted to the FDA that enrolled at least 150 patients in the intention-to-treat population. The data encompassed 25 trials and 20,013 patients with mNSCLC. The trials were submitted to the FDA between January 2003 and December 2016.
Analyses revealed a moderate association between OS at 12 months and OS HR and between OS at 9 months and OS HR.
No associations existed between progression-free survival (PFS) at 9 months and OS HR or overall response rate (ORR) at 6 months and OS HR.
Analysis of immunotherapy trials vs chemotherapy trials revealed an OS HR of 0.69 and PFS HR of 0.82. Targeted therapy trials vs chemotherapy trials revealed an OS HR of 0.98 and PFS HR of 0.48.
Overall survival at 12 months had the strongest association with OS HR but that may not be an ideal milestone marker for future trials. “Milestone rates may be useful as a complementary tool to summarize or interpret trial results, or as a secondary end point in exploratory studies,” concluded the researchers.
1. Blumenthal GM, Zhang L, Zhang H, et al. Milestone analyses of immune checkpoint inhibitors, targeted therapy, and conventional therapy in metastatic non-small cell lung cancer trials: a meta-analysis [published online June 15, 2017]. JAMA Oncol. doi: 10.1001/jamaoncol.2017.1029