Post-surgical cancer therapy holds promise

Keytruda for Carcinoma

Merck and Co.’s PD-1 inhibitor Keytruda appears to have potential for setting a new standard of post-surgical care for high-risk kidney care patients, according to a report by Angus Liu of Fierce Pharma that covered findings presented at the American Society of Clinical Oncology meeting.

While Pfizer’s kinase inhibitor Sutent has been approved since 2017 to help prevent tumors from returning in high-risk kidney cancer patients after surgery, its efficacy and safety are less than optimal. Keytruda could be an alternative. In patients with clear-cell renal cell carcinoma, treatment with Keytruda after surgery reduced the risk of returning disease or death by 32 percent compared with placebo. After two years, 77.3 percent of patients received Keytruda in the phase 3 Keynote-564 trial remained alive and disease-free, while 68.1 percent of patients in the placebo group were in that category.

It is the first time a PD-1/L1 inhibitor improved so-called disease-free survival for patients with high-risk kidney cancer, according to the report. ASCO Chief Medical Officer Julie Gralow, M.D. said that, if approved, Keytruda could become a new standard of care for clear-cell renal cell carcinoma. Approximately 70 percent of renal cell carcinomas are the clear-cell type. That degree of improvement in disease-free survival has triggered previous FDA approvals and is deemed clinically meaningful, according to Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories.

Two experts specializing in genitourinary cancers who were interviewed by SVB Leerink said a disease-free survival improvement of at least eight months would help to support Keytruda adoption in high-risk kidney cancer, even before key data on patient survival are ready, according to an investor’s note. While median disease-free survival data were premature, Keytruda will probably cross the eight-month threshold given historical clinical data from Sutent.

Sutent earned its adjuvant kidney cancer status based on data from the S-Trac trial, in which the Pfizer small-molecule drug reduced the risk of returning disease or death by 24 percent over placebo. Patients on Sutent lived a median 6.8 years without recurrence, a 1.2-year improvement over placebo, but that did not make Sutent the standard of care. Sutent is only approved for adjuvant kidney cancer in the U.S., and its use there has been “sporadic,” according to Ebbinghaus.

During an FDA advisory committee meeting in 2017, external experts voted 6-6 on using Sutent in adjuvant kidney cancer. The experts were split on the significance of the disease-free survival advantage and noted Sutent's 60 percent rate of side effects of grade 3 or above. About 28 percent of patients discontinued treatment. The FDA approved the drug anyway.

The degree of disease-free survival is higher for Keytruda in its own trial, and the side effect profile for single-agent anti-PD-1 is better than that of long-term use of a kinase inhibitor, Ebbinghaus explained. Side effects of grade 3 or above occurred in 32.4 percent of Keytruda patients in Keynote-564. On those two characteristics, Keytruda “will have an important role to play” in adjuvant kidney cancer, he said.