The Food and Drug Administration approved Keytruda in combination with Inlyta for the frontline treatment of patients with advanced renal cell carcinoma.
The approval is based on findings from the phase 3 KEYNOTE-426 trial, which demonstrated that the frontline combination significantly improved overall response rates, progression-free (time from treatment to disease progression or worsening) and overall survival compared with Sutent (sunitinib) in patients with advanced RCC. Moreover, data showed that Keytruda/Inlyta led to a 47% reduction in the risk of death versus Sutent.
This is the first anti—PD-1 therapy that is approved as part of a combination regimen that significantly improved overall survival, progression-free survival and overall response rate compared with Sutent in this patient population.
"This represents a new treatment option for patients with advanced renal cell carcinoma, who will now have access to Keytruda as part of a first-line combination regimen," said Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories, the developer of Keytruda. "Today’s approval reflects Merck’s commitment to patients with cancer and further supports the use of Keytruda to help improve survival outcomes for patients with advanced renal cell carcinoma."
In the open-label KEYNOTE-426 study (NCT02853331), 861 patients with newly diagnosed or recurrent stage 4 clear cell RCC were randomized 1:1 to receive Keytruda at 200 mg intravenously every three weeks for up to 35 cycles plus Inlyta at 5 mg orally twice daily or Sutent at 50 mg orally once daily for the first four weeks of each six-week cycle. Treatment was administered until disease progression, unacceptable toxicity, or if patients dropped out of the trial.
The median age was 62; 73% of patients were male and 27% were female. Patients were stratified by geographic region and by International Metastatic Renal Cell Carcinoma Database Consortium risk group as having favorable-, intermediate- or poor-risk disease.
The coprimary endpoints were overall and progression-free; secondary endpoints were overall response rate, duration of response, patient-reported outcomes and safety.
At a median follow-up of 12.8 months, results showed that the median overall survival was not reached in either arm. The median progression-free survival was 15.1 months for Keytruda/Inlyta and 11.1 months with Sutent. With the combination, there was a 31% reduction in the risk of disease progression.
The 12- and 18-month overall survival rates were higher with Keytruda/Inlyta than Sutent, at 89.9% versus 78.3% and 82.3% versus 72.1%, respectively. The 12-month and 18-month progression-free survival rates were also higher with Keytruda and Inlyta (59.6% and 41.1%) compared with Sutent (46.2% and 32.9%). The survival benefits were observed irrespective of PD-L1 status or risk group.
Additionally, the overall response rate was 59.3% with the combination and 35.7% with Sutent. The median duration of response was not reached in the Keytruda/Inlyta arm and was 15.2 months for Sutent. Treatment is ongoing in 59.0% of patients on the immunotherapy/TKI arm and in 43.1% of those on the Sutent arm.
Regarding safety, the incidence of all-grade side effects was comparable between the two arms, at 96.3% with the combination and 97.6% with Sutent. Grade 3 to 5 side effects were higher with Keytruda/Inlyta (62.9%) versus Sutent (58.1%). A total of 0.9% of side effects led to death in the combination arm versus 1.6% in the Sutent arm.
Moreover, 25.9% of patients who were treated with Keytruda/Inlyta discontinued treatment of either drug, compared with 10.1% of patients who discontinued Sutent. A total 8.2% of patients discontinued treatment with both Keytruda and Inlyta.
"Given the aggressive nature of the disease, many patients with advanced renal cell carcinoma need additional treatment options that can help improve survival outcomes," said Brian Rini, M.D., medical oncologist at Cleveland Clinic Cancer Center and professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. "(Keytruda) in combination with (Inlyta) offers an important new therapeutic option for physicians to consider when approaching initial treatment for patients newly diagnosed with advanced renal cell carcinoma."
This article appeared originally on OncLive, titled “FDA Approves Pembrolizumab/Axitinib Combo for Frontline RCC.”