Pictured: Glass front and sign of a Merck building/iStock, JHVEPhoto
A final, pre-specified analysis of the Phase III CLEAR/KEYNOTE-581 study showed that the combination of Merck’s Keytruda (pembrolizumab) with Eisai’s Lenvima (lenvatinib) has durable long-term survival benefits when used as a first-line treatment in patients with advanced renal cell carcinoma, the companies announced Thursday.
After four years of follow-up, the combination regimen significantly reduced the risk of death by 21%, as compared with Pfizer’s Sutent (sunitinib). In the Keytruda/Lenvima arm, overall survival (OS) rates at 24 and 36 months were 80.4% and 66.4%, respectively; in Sutent-treated patients, corresponding OS rates were 69.6% and 60.2%.
Beyond survival, the four-year follow-up data also demonstrated that Merck’s and Eisai’s treatment combination cut the risk of progression or death by 53% relative to Sutent. Objective response rate was 71.3% as opposed to 36.7% with Pfizer’s drug.
As for safety, the long-term data found no new safety signals. The tolerability profile of the Keytruda-Lenvima combo was consistent with that in the primary analysis, including a higher rate of treatment-related adverse events grade three or higher, as compared with Sutent (74.1% vs 60.3%).
Merck and Eisai will present these data at an oral abstract session at the upcoming 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2-6.
The Keytruda-Lenvima combination regimen won the FDA’s approval for the first-line treatment of advanced renal cell carcinoma in August 2021.
Frontline Standard in Advanced Cervical Cancer
Also being presented at ASCO are long-term data from the KEYNOTE-826 study, which assessed the value of adding Keytruda to standard chemotherapy, with or without Genentech’s (Roche) Avastin (bevacizumab), for the frontline treatment of metastatic, recurrent or persistent cervical cancer.
At around 40 months of follow-up, the Keytruda-chemotherapy combo reduced the risk of death across the entire study population by 37%. This survival benefit remained significant regardless of PD-L1 expression status, Merry Jennifer Markham, professor of medicine in the Division of Hematology and Oncology in the Department of Medicine at the University of Florida Health Cancer Center, said in a statement.
Progression-free survival was likewise better among patients treated with add-on Keytruda relative to placebo.
In terms of safety, Keytruda elicited a higher rate of adverse events grade three and above than placebo. The most common grade three side effects were anemia, neutropenia and hypertension.
“The results of this study solidify the addition of pembrolizumab to chemotherapy with or without bevacizumab in people with persistent, recurrent, or metastatic cervical cancer as the front-line standard of care for this disease,” Markham said.
Keytruda is already approved for the first-line treatment of cervical cancer, an indication it picked up in October 2021, though its use is restricted only to patients positive for PD-L1.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
