Keytruda-Inlyta Combo Continues to Improve Survival in Kidney Cancer

Use of the combination of Keytruda and Inlyta is associated with long-term survival benefits in patients with kidney cancer.

Treatment with Keytruda (pembrolizumab) combined with Inlyta (axitinib) continues to show long-term survival benefits in patients with renal cell carcinoma, compared to Sutent (sunitinib) alone.

The findings were recently presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

At a median follow-up of 42.8 months, the median overall survival (time that a patient with cancer is still alive) was 45.7 months in patients who received Keytruda and Inlyta compared with 40.1 months in those who received single-agent Sutent. The median progression-free survival (time during and after treatment when the patient lives without disease progression) was 15.7 months versus 11.1 months, respectively.

“(These data) represent the longest follow-up of a checkpoint inhibitor combined with a VEGF/VEGFR inhibitor for first-line clear cell (renal cell carcinoma),” said lead study author Dr. Brian I. Rini, a professor of medicine and the inaugural chief of Clinical Trials at Vanderbilt-Ingram Cancer Center in Nashville, during a presentation of the findings.

“Results of the final analysis of KEYNOTE-426 continue to support (Keytruda) plus (Inlyta) as standard of care for patients with previously untreated advanced clear cell (renal cell carcinoma),” added Rini.

The international, open-label, phase 3 KEYNOTE-426 study included 861 patients aged 18 years or older with treatment-naive, advanced renal cell carcinoma. Patients were randomized to receive either the combination (432 patients; median age, 62 years; 71.3% male) or single-agent Sutent (429 patients; median age, 61 years; 74.6% male).

Previous nephrectomy (surgery to remove one or both kidneys) had been performed in 82.6% of the combination group, and 72.9% of patients in this grouo had at least two sites of metastases (spread of cancer from primary site).

In the combination group, patients received 200 mg of Keytruda intravenously every 3 weeks for up to 35 cycles plus 5 mg of Inlyta orally twice daily. The other patients were treated with 50 mg of Sutent orally once daily for the first 4 weeks of each 6-week cycle.

Treatment was administered until disease progression, unacceptable toxicity, or if patients dropped out of the trial. Measuring overall survival and progression-free survival were the main goals of the study.

The follow-up range for the data reported at the ASCO Annual Meeting was a minimum of 35.6 months to a high of 50.6 months. At the time of follow-up, 14.5% of patients in the combination group were still receiving treatment, compared with 9.4% of patients in the Sutent group.

More than half (58.4%) of patients in the combination group received subsequent anticancer therapy, compared with 73% in the Sutent group.

Objective response rate (the rate of a measurable response to the treatment) at 42.8 months was 60.4% in the combination group compared with 39.6% in the Sutent group. The complete response and partial response rates were 10% versus 3.5% and 50.5% versus 36.1%, respectively.

The median time to response was 2.8 months with the combination versus 3 months with Sutent. The median duration of response (the length of time a tumor continues to respond to treatment without the cancer growing or spreading) was 23.6 months versus 15.3 months, respectively.

Regarding safety, Rini said, “The safety profile was comparable between (groups) and no new safety signals emerged.”

Updated safety data showed treatment-related side effects occurred in 96.3% of the combination group compared with 97.6% of patients in the Sutent group. “The only addition to this from previous presentations is proteinuria (increased levels of protein in the urine) has now reached 20% overall incidence in the (Keytruda) plus (Inlyta) arm,” said Rini.

The rates of serious, severe or life-threatening side effects were 67.8% versus 63.8%, respectively. There were four patient deaths in the Keytruda and Inlyta group compared with seven in the Sutent group.

Based on prior data from this trial, the Food and Drug Administration approved Keytruda plus Inlyta in April 2019 for use in the front-line setting for patients with advanced renal cell carcinoma.

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