Nearly one-third of solid tumor drug approvals in the last 12 years were for additions to existing regimens, which could increase therapy complexity, costs, and exposure to drug side effects, according to researchers at the 2023 ASCO Annual Meeting.

In a retrospective analysis, the investigators reviewed all drugs approved by the US Food and Drug Administration (FDA) for malignant solid tumors from January 2011 to December 2022. They sought to determine how many new approvals replaced or added to existing therapies.

“Single agents replacing previous therapies are ideal, but combination therapies with two or more active agents have been proposed to decrease drug resistance, promote mechanistic synergy, and/or have additive cytotoxic effects in cancer treatment,” researchers said. “However, approval of combination therapies may increase exposure to new and former drugs, leading to more costs and time commitments to patients.”

The authors looked at package inserts from the FDA’s website and analyzed data on all new and clinically meaningful indication changes. Excluded from the analysis were approvals for topical medications, precancerous conditions, hematologic conditions, primarily pediatric cancers, primary genetic syndrome neoplasms, biosimilars, and minor indication changes.

Out of 279 drugs approved during the study period, 247 indications met the researchers’ criteria. Approvals were most commonly for non-small cell lung cancer (21%, n = 52), breast cancer (11.3%, n = 28), and melanoma (8.9%, n = 22).

Small molecular targeted therapies and immunotherapy checkpoint inhibitors were the most common drug classes, with proportions of 40% (n = 99) and 34% (n = 84), respectively. Additionally, researchers found most approvals were indicated for the first-line (44.9%, n = 111), second-line (42.9%, n = 106), and adjuvant settings (6.9%, n = 17).

The findings indicate 167 of 247 approvals (67.6%) replaced an existing therapy to become a new, single treatment, while 80 approvals (32%) added to existing therapy. 

Among those that were added to existing therapies, 49 approvals (19.8%) were in combinations of at least 2 drugs, while 32 approvals (12.9%) were for regimens comprised of at least 3 drugs.

“When comparing single-agent vs combination regimen approvals, there was difference in cancer types, type of regimen, line of therapy, highest endpoints leading to approval, novel therapy, and type of drug approval (P < .05; test statistic > critical value). However, the year of approval, fast-track, and priority-review status were not statistically significant,” researchers found.

While most drug approvals over the last 12 years replaced or added a new standard, the authors concluded “a significant minority” added to existing regimens, signaling increased therapy complexity for patients with non-hematologic solid cancers.

Researchers warned this heightened complexity could increase the “potential time commitment for patients, costs, and exposure to therapies with notable side effects.”

Reference:
Rai MP, Chitkara A, Thawani R, Chen EY. Trends in FDA approval of solid tumor therapies with analysis of single-agent vs. combination therapies. J Clin Oncol. 2023;41(suppl 16; abstr e13659). doi:10.1200/JCO.2023.41.16_suppl.e13659