Eventual success rate and predictors of success for oncology drugs tested in phase I trials

Abstract

Previous estimates of the likelihood of a drug tested in phase I trials obtaining FDA clearance are out of date. In the intervening years, newer pharmaceuticals have been developed, resulting in new delivery systems and lines of therapies. We sought to explore and update these estimates by comprehensively searching drugs tested in phase I trials and to determine the factors associated with later receiving FDA approval. In a cross‐sectional analysis, we searched for anti‐tumor drugs tested in phase I trials and published in scientific journals or presented at hematology/oncology conferences. For each drug, we searched PubMed for phase II and phase III studies testing the drug for the same indication tested in phase I studies. We found 51 drug approvals; four were withdrawn. The probability of a drug tested in 2015 being approved by 2021 was 6.2%. Drugs tested as monotherapy were more likely to receive approval than drugs tested in combination, and monoclonal antibodies were more likely to receive approval than drugs of other mechanisms. In adjusted models, response rates higher than 40% in phase I studies, demonstrating an improvement in overall survival (OS) in phase III studies, and drugs tested as monotherapy were associated with receiving FDA approval. When looking at all drugs tested during a single year, most drugs were not approved, and among those that are approved, almost 8% are withdrawn. Response rates higher than 40%, testing a drug as monotherapy, and demonstrating an improvement in OS were associated with receiving FDA approval.

Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?

“…Responses were rapid, with nearly 90% demonstrating response by first tumor assessment and durable, with mOS and mediation duration of response both exceeding 2 years (26.1 and 25.6 months). Although efficacy in early-phase studies is rarely recapitulated in larger randomized trials, 11 the results are tantalizing and would represent a clear advancement in mUC if confirmed in the ongoing randomized trial (ClinicalTrials.gov identifier: NCT04223856) which randomly assigns unselected patients to the EV/pembrolizumab combination versus gemcitabine plus cisplatin or carboplatin. At the 2022 ESMO Congress, we saw initial results from cohort K of the EV-103 trial (ClinicalTrials.gov identifier: NCT03288545) which randomly assigned cisplatin-ineligible, previously untreated patients 1:1 to EV/pembrolizumab or EV alone.…”