Does biomarker use in oncology improve clinical trial failure risk? A large‐scale analysis

Abstract

Purpose To date there has not been an extensive analysis of the outcomes of biomarker use in oncology. Methods Data were pooled across four indications in oncology drawing upon trial outcomes from http://www.clinicaltrials.gov: breast cancer, non‐small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi‐state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states. Results Over 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7‐fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers. Conclusion This is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials.

IL-13Rα2 Status Predicts GB-13 (IL13.E13K-PE4E) Efficacy in High-Grade Glioma

“…While technical issues surrounding catheter placement and drug distribution are surmountable in future studies by optimizing catheter design and positioning of potentially multiple catheters, there was limited consideration of target expression for patient inclusion [ 37 , 70 ]. A large scale analysis of clinical trials utilizing biomarkers found significant improvement in trial success relative to no biomarker inclusion criteria [ 71 ]. Consistent with this idea, we compared IL-13Rα2 mRNA and protein levels from homogeneous cell populations, which showed that gene expression correlates with IL-13Rα2 protein status.…”

The Effect of Biomarker Use on the Speed and Duration of Clinical Trials for Cancer Drugs

“…Given the reduction in risk of clinical trial failure in the 4 indications described in Parker et al, 9 we hypothesized that the use of biomarkers in the inclusion or exclusion criteria of clinical trials would also have an impact on the duration of clinical trials and would affect the length of time spent between consecutive phases of the trials (eg, gap between the end of a phase I trial and start of a phase II trial). To compare between the 2 biomarker groups, the heatmap visualization was supplemented with the average durations of each trial phase and time gap between the trial phases, stratified by biomarker use, indication and biomarker type.…”

“… 6-8 An article by Parker et al studied 4 cancer indications and trials utilizing biomarkers to create cancer therapies and observed that the use of biomarkers such as HER2 in breast cancer resulted in a 5-fold reduction in clinical trial risk. 9 However, biomarkers also introduce challenges such as increased trial complexity 10 and unknown patient outcomes for exploratory biomarkers. 11 An important aspect that has not yet been extensively explored is how biomarkers may affect timelines in oncology drug development.…”

Molecular Biomarkers in Cancer

“…Big challenges remain in the process of cancer biomarker development, especially the need to generate high levels of evidence of a cancer biomarker value. Recently, Parker et al [ 177 ] performed the first extensive analysis of the outcomes of cancer biomarker use. Interestingly, they found statistical evidence that biomarker usage has a substantial clinical benefit in cancer patients, even when analyzing biomarkers not yet approved by regulatory authorities.…”