Study Results Indicate Precision Therapies Make Up Approximately Half of FDA-Approved Oncology Drugs

Between 1998 and 2022, approximately 43% of the 198 new oncology drugs approved by the FDA were precision oncology therapies. The use of these therapies is guided by biomarker testing. To quantify the expansion and impact of precision oncology, the authors of a study published in Cancer Discovery reviewed these FDA-approved oncology drugs.

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“For this study, we mark the beginning of the field of precision oncology as 1998 with the approval of trastuzumab (Herceptin; Genentech), 1 of the first molecularly targeted therapies indicated for HER2-positive breast cancer. Since then, the field has exponentially grown with the discovery of novel biomarkers and corresponding drug approvals, thanks in part to a progressive decrease in the cost of genomic sequencing and improvements in sequencing technology,” said senior study author Debyani Chakravarty, PhD, assistant attending molecular geneticist in the Department of Pathology and Laboratory Medicine, lead scientist of the precision oncology knowledge base OncoKB at Memorial Sloan Kettering Cancer Center, in a press release. “To our knowledge, there has not been a systematic assessment of how much this field has grown and the extent to which its expansion has benefitted patients with cancer.”

In the second part of the study, 2 versions of OncoKB, the first somatic tumor mutation database to be recognized by the FDA, were implemented in 2017 and 2022 to determine the clinical actionability of the genetic alterations identified by the MSK-IMPACT sequencing array in a set of 47,271 solid tumor samples. Further, the authors had determined whether a certain mutation in a patient’s tumor was considered predictive of response to an investigational drug in 2017, and it was then recognized as a biomarker predictive of response to a drug approved by the FDA in 2022.

Of the 198 new oncology drugs approved by the FDA, 82.8% (166 of 198) were classified as molecularly targeted therapies. Although these drugs’ mechanism of action is known, they do not require biomarker testing for patient selection. Further, approximately 43% (86 out of 198) were classified as precision oncology drugs—including kinase inhibitors, monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors—that require genomic biomarker screening for patient selection.

“The highest number [of FDA approvals] was registered in 2020, with 12, and the number appears to drop in 2021 and 2022, suggesting that we may have reached the peak of single biomarker-based precision oncology therapies,” said Chakravarty in the press release. “This finding also emphasizes the need for innovative combination approaches that can address multiple genomic alterations, as well as targeted therapies effective in patients whose tumors are driven by alterations in common tumor suppressor genes or transcription factors.”

Researchers further classified precision oncology therapies into 4 categories based on the novelty of their mechanism of action, and they found that 42% of these drugs worked through a similar mechanism of action either as a previously approved therapy or targeted resistance to an existing drug.

“The majority of these therapies target only 7 biomarkers, highlighting the narrow scope of precision oncology drug development during this period,” Chakravarty noted in the press release.

Results from the second part of the study showed a fraction of patient samples had genomic alterations which made them eligible for either treatment with standard-of-care precision oncology therapies or for enrollment in a clinical trial with clinical data that nearly doubled (18.1% to 35.9%) from 2017 to 2022. Similarly, there was an approximate 50% decrease (from 44.2% to 22.8%) in the small number of samples with oncogenic alterations that are currently non-actionable.

“Despite the dramatic growth of the field, the clinical impact of precision oncology is still debated. By thoroughly and systematically mapping out the landscape of precision oncology, our study revealed that these therapies are a mainstay of current oncology care,” Chakravarty said in the press release. “Unfortunately, these drugs can be extremely expensive, and insurance coverage often dictates whether a patient will receive them. Our findings support that coverage of precision oncology therapies is essential and should not be available to only a select few.”

Limitations of the study include a lack of information on germline mutations which determine eligibility for particular therapies, the lack of diversity in the patient population, and the study only being based on United States FDA drug approvals. Another limitation of the study is the lack of information on whether patients received the precision therapy they were eligible for, according to the authors.

“Eligible patients may not receive a precision oncology drug for several reasons related to their disease or to our current health care landscape,” said Chakravarty in the press release. “It is also important to note that not all patients treated with a genomic-matched therapy will benefit equally.”

Reference

American Association for Cancer Research. Nearly Half of Oncology Drugs Approved Since 1998 Are Precision Therapies. News release. October 18, 2023. Accessed October 17, 2023. Email.