Nearly Half of Oncology Drugs Approved Since 1998 Are Precision Therapies

A study by Debyani Chakravarty, PhD. and Sarah P. Suehnholz, Ph.D. published in Cancer Discovery reveals that approximately 43% of the 198 new oncology drugs approved by the U.S. Food and Drug Administration (FDA) between 1998 and 2022 are precision oncology therapies. These therapies are guided by biomarker testing and are most effective for specific subsets of patients. Imatinib has a 95% response rate in patients with chronic myeloid leukemia and extends quality-adjusted life by about 9 years; venetoclax has an 80% response rate in patients with chronic lymphocytic leukemia who have a 17p deletion.

The study, conducted by researchers from Memorial Sloan Kettering Cancer Center (MSK), marks the beginning of the field of precision oncology in 1998 with the approval of trastuzumab (Herceptin) for HER2-positive breast cancer. Since then, the field has experienced significant growth due to advancements in biomarker discovery, drug approvals, and improvements in genomic sequencing technology. The researchers quantified the expansion and impact of precision oncology by reviewing FDA-approved oncology drugs and assessing the clinical actionability of genetic alterations in solid tumor samples. The study found that only 8% of patients with cancer are eligible for precision medications approved as of January 2018 and only 5% would actually benefit from them.

They found that 82.8% of the approved drugs were molecularly targeted therapies, while 43% were precision oncology drugs. This analysis showed a gradual increase in FDA approvals of precision oncology therapies until 2017, followed by a rapid increase through 2022. However, the number of approvals appears to have peaked in 2020 and has since declined, indicating a potential saturation of single biomarker-based precision oncology therapies. According to the study, 43% of the 198 new oncology drugs approved by the FDA between 1998 and 2022 were precision oncology therapies.

This finding underscores the importance of innovative combination approaches that can address multiple genomic alterations, as well as targeted therapies that are effective in patients with tumors driven by common tumor suppressor genes or transcription factors. Tumor suppressor genes are important regulators of cellular growth and their mutations can lead to uncontrolled cell growth and cancer formation. This research highlights the importance of combining therapies to target multiple genomic alterations and to treat tumors driven by tumor suppressor genes or transcription factors.

To evaluate the level of innovation in the field, the researchers categorized precision oncology therapies into four groups based on the novelty of their mechanism of action. They discovered that 42% of these drugs functioned in a similar way to previously approved therapies or targeted resistance to existing drugs. This suggests that although precision oncology therapies are new, they are not always truly innovative. Furthermore, the researchers highlighted the need for more research and development in this field.

"Our analysis revealed that the majority of these therapies only target seven biomarkers, indicating the limited scope of precision oncology drug development during this time period," added Chakravarty. "Several targets have remained untargetable since 1998. We are starting to make progress with some, such as targeting specific mutant forms of KRAS, but we must continue expanding the number of actionable genetic alterations."

Results from the second part of the study showed that the percentage of patient samples with genomic alterations eligible for treatment with standard-of-care precision oncology therapies, or for participation in a clinical trial with promising clinical data, nearly doubled from 2017 to 2022 (from 18.1% to 35.9%).

Meanwhile, the fraction of samples with non-actionable oncogenic alterations decreased by almost 50% (from 44.2% to 22.8%). This decrease in the percentage of samples with non-actionable oncogenic alterations is a positive sign that the testing methods are becoming increasingly accurate. This suggests that fewer patients are being incorrectly identified as having a tumor when in fact, they do not.

"Despite the significant growth of the field, the clinical impact of precision oncology is still a subject of debate. Our comprehensive mapping of the precision oncology landscape revealed that these therapies are now a vital part of current oncology care," said Chakravarty.

"Unfortunately, these drugs can be prohibitively expensive, and access to them is often determined by insurance coverage. Our findings support the importance of ensuring that precision oncology therapies are accessible to all, rather than just a select few."

The study also emphasized the value of universal genetic testing for the development of treatments that target rare genomic alterations, regardless of the site of tumor origin, according to Chakravarty.

The authors noted that one limitation of their analysis is the lack of information on whether eligible patients actually received the precision therapy for which they were eligible.

"There are various reasons why eligible patients may not receive a precision oncology drug. This may be related to their disease or the current healthcare landscape," said Chakravarty. "It is also important to acknowledge that not all patients treated with a genomic-matched therapy will benefit equally."

Additionally, the study did not gather information on germline mutations that determine eligibility for certain targeted therapies, and the patient population studied was not diverse.

The analysis was based on U.S. FDA drug approvals, and different countries may have different regulatory statuses and approaches to precision oncology, the authors explained." Therefore, the authors recommend that countries should develop their own strategies for precision oncology, in order to ensure the best outcomes for patients. They suggest creating a comprehensive framework for regulatory approval, as well as developing resources and infrastructure to support precision oncology. Ultimately, these strategies should aim to ensure the availability of safe and effective precision oncology treatments to patients around the world.