Assessment of New Molecular Entities Approved for Cancer Treatment in 2020

The COVID-19 pandemic has brought unprecedented disruptions to trials and drug development.¹ The US Food and Drug Administration (FDA) has had to spend its resources reviewing SARS-CoV-2 therapies and vaccines.² Despite these challenges, the FDA commissioner has stated that the FDA is “full speed ahead” in 2020 on the approval of novel cancer drugs.³ To assess this claim, we sought to survey all new molecular entities (NMEs) approved for cancer treatment in 2020.

In this cross-sectional study, we reviewed the FDA Hematology/Oncology Approvals website⁴ to ascertain all hematology/oncology drugs approved in 2020. The authors (C. S. and V. P.) determined which drugs were novel, defined as having no prior FDA approval for a similar or different indication. New formulations of previously approved drugs (eg, oral formulations of previously approved intravenous formulations) were not considered to be novel drugs. We recorded the response rate, complete response rate, duration of response, progression-free survival, and overall survival as reported in the FDA prescribing information for each drug. In the event that a given approval was based on 2 different trials or 2 separate arms of a trial, we recorded the mean response between the 2 trials. The type of FDA approval (accelerated or regular) and the design of the trial were noted. Accelerated approvals require further proof of efficacy in improving overall or progression-free survival.

This study was not submitted for institutional review board approval because it did not use personal health care information and all study data are publicly available (Common Rule, 82 FR §7149).⁴ This report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies.

There were 18 NMEs approved for cancer treatment in 2020 as determined by the authors (Table). This was more than the 13 NMEs approved for cancer in 2019, and similar to 2018.⁴

Two drugs (11%) were approved based on an improvement in overall survival compared with a placebo-controlled arm. These include ripretinib, which in trial had a 15.1-month overall survival in metastatic gastrointestinal stromal tumor compared with a 6.6-month survival for patients receiving placebo, and tucatinib, which when used in combination with capecitabine and trastuzumab resulted in a mean overall survival of 21.9-months in metastatic ERBB2 (formerly HER2)–positive breast cancer compared with 17.4 months in the capecitabine and trastuzumab arm. The remaining 16 novel cancer drug approvals were based on response rate or progression-free survival. Of all the novel cancer therapies approved in 2020, the median response rate (ie, partial plus complete response rate) was 49.7% (range, 9%-87%); the complete response rate ranged from 0% to 62%, with a median of 3% (Figure).

Only 4 (22%) of the approvals were based on a randomized placebo-controlled trial. The remaining 14 approvals (78%) were based on uncontrolled, single-arm phase I/II trials. Eleven of these were accelerated approvals and will require further efficacy data.

More NMEs were approved by the FDA for cancer in 2020 than in 2019. However, most approved NMEs were based upon surrogate end points with uncertain effects on survival and quality of life.⁵ The majority of approvals were based upon uncontrolled, single-arm clinical trials, and will require postmarket efficacy testing.⁶ Approximately half of patients given one of these novel drugs approved in 2020 will have a demonstratable tumor response. The authors acknowledge that this study is limited in that we only reviewed 1 year of FDA drug approvals. Additionally, future trial data regarding these medications may become available, rendering the observations here no longer relevant.

Accepted for Publication: April 8, 2021.

Published: May 28, 2021. doi:10.1001/jamanetworkopen.2021.12558

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Smith CEP et al. JAMA Network Open.

Corresponding Author: Vinay Prasad, MD, MPH, University of California, San Francisco, 550 16th St, San Francisco, CA 94158 (vinayak.prasad@ucsf.edu).

Author Contributions: Dr Prasad had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Both authors.

Acquisition, analysis, or interpretation of data: Smith.

Drafting of the manuscript: Smith.

Critical revision of the manuscript for important intellectual content: Both authors.

Administrative, technical, or material support: Smith.

Supervision: Prasad.

Conflict of Interest Disclosures: Dr Prasad reported receiving grant funding from Arnold Ventures during the conduct of the study; he reported receiving publishing royalties from Johns Hopkins University Press, Medscape, and MedPage; he reported receiving consulting fees from UnitedHealthcare; he reported receiving speaking fees from Evicore, New Century Health, and Patreon Plenary Session podcast outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by Arnold Ventures.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.