A cross-sectional study of cancer drug indications granted accelerated approval, which was published in JAMA Network Open, found that prescribing increased more after accelerated approval than after conversion to regular approval. Parikh et al also noted that off-label prescribing after accelerated approval was rare.
The investigators commented: “Robust prescribing for accelerated approval indications suggests that many oncologists are unconcerned or unaware about the provisional evidence underlying accelerated approval. In contrast, modest prescribing increases after conversion to regular approval may suggest that oncologists do not distinguish between accelerated approval and regular approval or attach low incremental value to regular approval compared with accelerated approval. Another factor contributing to limited increase in uptake following conversion to regular approval may be that the accelerated approval drug had already been approved for earlier lines of treatment or that other analogous drugs received approval in the same treatment line.”
Study Details
The study included 63,434 patients who were diagnosed with advanced solid malignant neoplasms and received at least one systemic therapy. Drug utilization data were derived from patient-level electronic health records in the Flatiron Health Database.
Information on 161 accelerated approval indications was obtained from U.S. Food and Drug Administration (FDA) databases. Within the data set, the investigators identified 29 indications with at least 30 eligible patients in both the preapproval and postapproval periods; eligible patients were aged at least 18 years and met cancer-, line of therapy–, and biomarker-specific criteria for an indication.
For each indication, the primary outcome was the mean percentage point difference in the proportion of eligible patients who initiated a line of therapy with the corresponding drug within 6 months prior to and following accelerated or regular approval. The investigators also examined the off-label use of drugs under accelerated approval, particularly in treatment line– and biomarker-discordant scenarios.
Key Findings
Among the 16 eligible accelerated approval indications that transitioned to regular approval (55.2%), prescribing increased by 23% (mean [standard deviation], 6% [15%] to 30% [18%]) and 1 (mean [standard deviation], 33% [23%] to 34% [23%]) percentage points after accelerated and regular approval, respectively. The difference in prescribing change between accelerated and regular approval was 22 percentage points (95% confidence interval [CI] = 19–26 percentage points; P < .001).
Prescribing responses to accelerated approval appeared to vary by indication; alectinib in non–small cell lung cancer was found to have the largest increase of 55 percentage points. According to the investigators, such responses were larger for indications that were vs were not eventually granted regular approval (23 [95% CI = 13–34] vs 7 [95% CI = 3–12] percentage points).
The investigators furthermore noted that off-label prescribing increases after accelerated approval were small, with a 3–percentage point increase for treatment line–discordant use and a 1–percentage point increase for biomarker-discordant use.
“Our findings, along with evidence that prices do not increase after conversion to regular approval, suggest that drug manufacturers have little incentive to complete accelerated approval postmarketing requirements quickly,” the investigators concluded. “Timely confirmatory evidence for accelerated approval drugs is important given the rapidity of accelerated approval uptake observed.”
Ravi B. Parikh, MD, MPP, of Winship Cancer Institute, Emory University, Atlanta, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by a grant from Arnold Ventures. For full disclosures of the study authors, visit jamanetwork.com.
