FDA Reviews Accelerated Approvals for Keytruda, Opdivo, and Tecentriq in Multiple Cancers
Key Insights
The FDA is re-evaluating the accelerated approvals of Merck's Keytruda, Bristol-Myers Squibb (search)'s Opdivo, and Roche's Tecentriq across six cancer types due to failed confirmatory trials.
ODAC will discuss Tecentriq with Abraxane for advanced triple-negative breast cancer (search), focusing on alternative confirmatory studies after the Impassion131 trial failure.
Keytruda and Tecentriq's first-line treatment status for urothelial carcinoma (search) is under review, considering the approval of Bavencio as a first-line maintenance therapy.
The FDA's Oncologic Drugs Advisory Committee (ODAC) is scrutinizing the accelerated approvals of three major cancer immunotherapies—Merck & Co (search)'s Keytruda (pembrolizumab), Bristol-Myers Squibb (search)'s Opdivo (nivolumab), and Roche's Tecentriq (atezolizumab)—across six cancer indications. This review comes after confirmatory trials failed to validate the promising data that initially supported these approvals, raising questions about their continued availability for patients.
Scrutinizing Accelerated Approvals
These drugs initially received accelerated approval based on encouraging mid-stage study results, aligning with the FDA's efforts to expedite access to novel therapies. However, subsequent larger trials failed to confirm these early benefits, prompting the FDA to re-evaluate their market status. Richard Pazdur, head of the FDA's Office of Oncologic Diseases, emphasized the importance of this review, stating it "creates an opportunity for external oncology experts and patients with cancer to share input and perspective with the FDA."
Tecentriq and Triple-Negative Breast Cancer
On April 27, ODAC focused on Tecentriq in combination with Abraxane (nab-paclitaxel) for advanced triple-negative breast cancer (search) (TNBC (search)) with PD-L1 expression. This indication was initially approved in 2019 based on the Impassion130 study. However, the follow-up Impassion131 trial, using Tecentriq with regular paclitaxel, yielded disappointing results, even suggesting potentially better outcomes with paclitaxel alone. The FDA briefing documents indicate that discussions will center on identifying alternative confirmatory studies to support this indication.
Keytruda, Tecentriq, and Urothelial Carcinoma
On April 28, the committee shifted its attention to Keytruda and Tecentriq as first-line treatments for urothelial carcinoma (search) (UC (search)) patients ineligible for cisplatin-containing chemotherapy. Both drugs received approval for this indication in 2017. The landscape has since changed with the full FDA approval of Merck KGaA and Pfizer's Bavencio (avelumab) as a first-line maintenance therapy, potentially raising the evidentiary bar for Keytruda and Tecentriq to maintain their approved status.
Keytruda and Hepatocellular Carcinoma
On April 29, ODAC reviewed Keytruda for third-line treatment of recurrent, PD-L1-expressing gastric or gastroesophageal junction adenocarcinoma (search), initially cleared in 2017. Additionally, the approvals of Keytruda and Opdivo as second-line therapies for hepatocellular carcinoma (search) (HCC (search)) previously treated with sorafenib were examined. These approvals, granted in 2018 and 2020, are now under scrutiny to determine if their clinical benefits have been confirmed in larger, controlled trials.
Historical Context and Implications
Since 1992, the FDA has granted over 155 accelerated approvals for cancer drugs, with only 10 (6%) being withdrawn. Pazdur and Julia Beaver noted in the New England Journal of Medicine that a small percentage of drugs failing to confirm initial benefits should be viewed as "an expected trade-off in expediting drug development that benefits patients with severe or life-threatening diseases." The outcomes of these ODAC meetings could significantly impact the treatment landscape for these cancers, potentially leading to the withdrawal of certain indications or requirements for additional clinical trials.