Nearly Half of Oncology Drugs Approved Since 1998 Are Precision Therapies
As the number of targeted cancer therapeutics has increased, the percentage of tumors carrying molecular alterations eligible for treatment by those drugs nearly doubled from 2017 to 2022.
Precise, biomarker-guided therapies made up almost half the anti-cancer therapeutics approved by the U.S. Food and Drug Administration (FDA) from 1998 to 2022, according to a study published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).
The authors marked the approval of trastuzumab (Herceptin) in 1998 as the beginning of the field of precision oncology, the use of drugs that are most effective in patients with specific molecular characteristics identified by molecular profiling.
“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 author Debyani Chakravarty, PhD, assistant attending molecular geneticist in the Department of Pathology and Laboratory Medicine and lead scientist of the precision oncology knowledge base OncoKB at Memorial Sloan Kettering Cancer Center (MSK).
FDA approved 198 anticancer therapeutics from 1998 to 2022. Approximately 43 percent of them were classified by the authors as precision oncology drugs, including kinase inhibitors, monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors, among others, all of which require genomic biomarker screening for patient selection, the authors wrote.
The analysis showed a slow expansion in the rate of FDA approvals of precision oncology therapies from 1998 to 2017 and a rapid increase from 2017 to 2022.
“The highest number was registered in 2020, with 12 FDA approvals, 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. “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.”
To assess innovation in the field, the researchers further classified precision oncology therapies into four categories based on the novelty of their mechanism of action. They found that 42 percent of these drugs worked through a similar mechanism of action as a previously approved therapy or targeted resistance to an existing drug.
“The majority of these therapies target only seven biomarkers, highlighting the narrow scope of precision oncology drug development during this period,” added Chakravarty. “Several targets have remained undruggable since 1998. We are now making inroads with some, for example, targeting specific mutant forms of KRAS, but we need to continue to expand the number of actionable genetic alterations.”
Furthermore, the study showed that the fraction of patient samples carrying genomic alterations that make them eligible for treatment with standard-of-care precision oncology therapies or for enrollment in a clinical trial with promising clinical data nearly doubled (from 18.1 percent to 35.9 percent) from 2017 to 2022. In parallel, there was a decrease of almost 50 percent (from 44.2 percent to 22.8 percent) in the fraction 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,” said Chakravarty. “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.”
Another aspect highlighted by this study is the importance of universal genetic testing that can help develop treatments targeting rare genomic alterations regardless of the site of tumor origin, added Chakravarty.
According to the authors, one limitation of their analysis is that it does not have information on whether patients actually received the precision therapy for which they were found to be eligible.
“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. “It is also important to note that not all patients treated with a genomic-matched therapy will benefit equally.”
Other limitations include the low diversity of the patient population studied and the fact that the analysis was based on U.S. FDA drug approvals and, therefore, does not reflect the regulatory status and approaches to precision oncology in other countries.
