Preclinical Metrics Correlate With Drug Activity in Phase II Trials of Targeted Therapies for Non-Small Cell Lung Cancer
JournalFrontiers in Oncology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractNovel oncology drugs often fail to progress from preclinical experiments to FDA approval. Therefore, determining which preclinical or clinical factors associate with drug activity could accelerate development of effective therapies. We investigated whether preclinical metrics and patient characteristics are associated with objective response rate (ORR) in phase II clinical trials of targeted therapies for non-small cell lung cancer (NSCLC). We developed a reproducible process to select a single phase II trial and supporting preclinical publication for a given drug-indication pair, which we defined as the pairing of a small molecule inhibitor (e.g., crizotinib) with the specific patient population for which it was designed to work (e.g., patients with an ALK aberration). We demonstrated that robust drug activity in mice, as measured by change in tumor size, is independently associated with improved ORR in phase II clinical trials. The number of mice utilized in experiments, the number of publications referencing the drug for NSCLC before the phase II clinical trial, and whether the drug was approved for a cancer other than NSCLC also significantly correlated with ORR. Among clinical characteristics, sex, race, histology, and smoking history were significantly associated with ORR. Further research into metrics that correlate with drug activity has the potential to optimize selection of novel therapies for clinical trials and enrich the drug development pipeline, particularly for patients with targetable genetic aberrations and rare cancers.
non-small cell lung cancer
patient derived (tumor) xenograft model
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/14147