Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Patient Exposure to Anticancer Drugs Subsequently Withdrawn from the FDA Accelerated Approval Programme Due to Lack of Benefit

Findings from a cross-sectional study
09 Mar 2023
Bioethical Principles and GCP;  Therapy

In a cross-sectional study that evaluated patient exposure to anticancer drugs withdrawn from the US Food and Drug Administration (FDA) Accelerated Approval programme, among 5 oncology indications, 26.1% of eligible treatment initiations involved an accelerated approval indication subsequently withdrawn due to a lack of benefit. Given the growth of withdrawals due to negative confirmatory studies and emerging evidence on the high spending associated with accelerated approved drugs, it is critical to balance early access against population-level exposure to anticancer treatment with no benefit over standard-of-care. The findings are published by Dr. Ravi B. Parikh of the Perelman School of Medicine, University of Pennsylvania in Philadelphia, PA, US and colleagues on 23 February 2023 in the JAMA Oncology.

The authors wrote in the background that between 2009 and 2022, the FDA approved 48 drugs for 66 oncology-related indications under the Accelerated Approval programme. Indications granted accelerated approval based on surrogate endpoints are subsequently required to confirm clinical benefit. They estimated the proportion of patients who received treatment for 5 oncology-related indications later withdrawn after failure to confirm efficacy under the accelerated approval programme.

This cross-sectional study included patients with advanced or recurrent breast, bladder, hepatocellular, gastric, or small cell lung cancer between 18 May 2016 and 8 March 2022, treated with at least 1 line of systemic treatment. The study team analyzed accelerated approval indications with subsequently published negative phase III confirmatory studies and indication withdrawal. These drugs had additional biomarker-specific, cancer-agnostic indication approvals, such that they were available for use before accelerated approval and continued to be available after accelerated approval withdrawal. Race and ethnicity were included as covariates because minority status is associated with decreased access to novel treatment. The primary outcome was initiation of accelerated approved treatment as a proportion of all indication-specific treatment initiations.

The cohort included 4342 patients who received 6560 eligible lines of treatment. Median age was 70 years (range, 24-85). There were 1639 females (39%) and 2649 males 2649 (61%); majority were White (67%) and 85% received care at community practices. The median time from accelerated approval to indication withdrawal was 46 months (range, 12-58).

Between accelerated approval and subsequent withdrawal, 1361 oncology treatment initiations (26.1%) involved an accelerated approved treatment that was subsequently withdrawn of which 23.1% in triple-negative breast cancer, 22.5% in bladder cancer, 38.8% in hepatocellular carcinoma, 41.4% in gastric cancer, and 23.6% in small cell lung cancer. Prevalence of accelerated approved drug initiations was higher between accelerated approval and negative study publication than between negative study publication and withdrawal.

The authors concluded that an expected trade-off exists between accelerated access to promising anticancer drugs and the withdrawal of some indications. Earlier access and more rapid FDA responses to negative confirmatory study data, which is a key proposal of the Accelerated Approval Integrity Act proposed in March 2022, may minimise exposure to treatments granted accelerated approval, but for which a lack of benefit has been shown subsequently.

The authors acknowledged Flatiron Health for access to the data.


Parikh RB, Hubbard RA, Wang E, et al. Exposure to US Cancer Drugs With Lack of Confirmed Benefit After US Food and Drug Administration Accelerated Approval. JAMA Oncology; Published online 23 February 2023. doi:10.1001/jamaoncol.2022.7770

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.