1703P - Value of molecular targets and genome-targeted cancer therapies FDA-approved, 2015-2022

Background

Genome-targeted cancer drug approvals have increased, offering personalized therapy at high cost. We assessed genome-targeted cancer drugs to determine the validity of the targets and clinical benefits identified in the pivotal clinical trials.

Methods

We identified trials FDA-designated as pivotal that supported genome-targeted cancer drug approvals between 2015-2022. From drug labeling and publications, we extracted characteristics of the trials. Strength of evidence supporting molecular targetability was assessed by the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Clinical benefit for approved indications was evaluated by the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) with substantial benefit defined as grade A or B for curative and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT level I-A and I-B associated with substantial clinical benefit were rated as high benefit.

Results

Among 50 molecular-targeted drugs approved for 84 indications, 45 (54%) were based on phase I/II trials and 45 were supported by single-arm studies. The most common primary endpoint (46, 55%) was response rate (median 57%, median duration of response 11.1 months). Among the 84 pivotal trials, 38 (45%) had I-A and 32 (38%) had I-B ESCAT targetability score; 24 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Overall, 24 indications (29%) were high-benefit genomic-based cancer treatments.

Conclusions

Fewer than one-third recently approved molecularly-targeted cancer therapies demonstrated high patient benefits. Data often evolve after marketing, but when new cancer treatments are first approved based on exploratory analyses and anti-tumor activity alone, benefit frameworks like ESMO-MCBS and ESCAT can help identify the minority of therapies with the best clinical potential.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Funded by the Kaiser Permanente Institute for Health Policy, Dr. Kesselheim and Dr. Avorn’s work also supported by Arnold Ventures.

Disclosure

A. Tibau: Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Training: Lilly, Pfizer. All other authors have declared no conflicts of interest.