“These results continue to support pembrolizumab (Keytruda) plus axitinib (Inlyta) as a standard of care for patients with previously untreated advanced RCC,” said lead study author Dr. Elizabeth R. Plimack.
Updated results of the phase 3 KEYNOTE-426 trial presented during the 2020 ASCO Virtual Scientific Program showed that Keytruda (pembrolizumab) in combination with Inlyta (axitinib) continued to demonstrate significant improvements in progression-free survival (PFS) and overall survival (OS) compared to Sutent (sunitinib) in patients with previously untreated, advanced renal cell carcinoma.
“These results continue to support pembrolizumab plus axitinib as a standard of care for patients with previously untreated advanced RCC,” lead study author Dr. Elizabeth R. Plimack, chief of the Division of Genitourinary Medical Oncology and director of Genitourinary Clinical Research at Fox Chase Cancer Center, said during a presentation of the data.
Based on earlier findings of the KEYNOTE-426 trial, the Food and Drug Administration in 2019 approved the combination of Keytruda and Inlyta for the frontline treatment of patients with advanced RCC.
The data the approval was based on demonstrated that, at a median follow-up of 12.8 months, patients who received the combination had a 47% reduction in the risk of death compared to those who received Sutent. Additionally, patients who received the combination had a 31% reduction in the risk of disease progression or death compared to Sutent. Keytruda in combination with Inlyta was also associated with a higher overall response rate (59.3%) compared to those who received Sutent alone (35.7%). Patients in either arm did not reach a median OS.
The approval marked the first time that an anti—PD-1 therapy became available as part of a combination regimen that significantly improved OS, progression-free survival (PFS), and ORR compared with Sutent in this patient population.
The open-label KEYNOTE-426 trial consisted of 861 patients (median age, 62 years; 73% male) with newly diagnosed or recurrent stage 4 clear cell RCC who were randomized 1:1 to receive Keytruda at 200 milligrams (mg) intravenously every three weeks for up to 35 cycles plus Inlyta at 5 mg orally twice daily (432) or Sutent at 50 mg orally once daily for the first four weeks of each six-week cycle (429). Patients continued to receive treatment until disease progressed, an unacceptable toxicity was reached, or they dropped out of the trial.
More than half of the patients (51.7%) in the study were from countries outside of North America (24.1%) and western Europe (24.4%). Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), 31.2% of patients had favorable-risk disease, 56.2% had intermediate-risk disease, and 12.6% had poor-risk disease.
In the analysis presented at the 2020 ASCO Virtual Scientific Program, the data cutoff date was 23 months of minimum follow-up.
The updated findings show that patients who received the combination had not yet reached a median OS, whereas patients who received Sutent reached a median OS of 35.7 months. One-year and two-year OS rates were 90% and 74% in those who received the combination and 79% and 66% with Sutent, respectively. Additionally, median PFS in the intent-to-treat population was 15.4 months in the combination arm compared to 11.1 months in the Sutent arm, which lead to a 29% reduction in the risk of disease progression or death. One-year and two-year PFS rates were 60% and 38% with Keytruda and Inlyta vs. 48% and 27% with Sutent, respectively.
The updated results also show that 22.8% of patients remain on Keytruda and Inlyta, while 72.7% had discontinued the combination therapy. These numbers were similar in the Sutent arm, where 17.9% remain on therapy and 82.1% had discontinued treatment.
The longer follow-up data also demonstrated improvements in ORR in the ITT population, which was 60.2% in those who received Keytruda and Inlyta compared to 39.9% in the Sutent arm. Patients who received the combination demonstrated a higher median duration of response (23.5 months) than those who received Sutent (15.9 months).
“We see with extended follow-up that the curves remain separated. The difference in OS remains statistically significant,” Plimack said regarding the OS data in the ITT population. “An important point to make about the 24-month landmark is that this is the point at which patients on the study ceased receiving infusions of pembrolizumab, and were allowed, per protocol, to either continue off both therapies or on axitinib alone. Further evaluation of data beyond this cutoff will be critical in understanding the implications of infusional treatment-free survival in this patient population.”
Most patients in both the combination arm (96.3%) and Sutent arm (97.6%) reported experiencing a treatment-related side effect, regardless of severity. The most common side effects patients reported included diarrhea, hypertension, hypothyroidism, fatigue, decreased appetite and nausea.
More severe treatment-related side effects — rated as grade 3 to grade 5 – occurred in 66.9% of patients receiving the combination vs. 62.4% receiving Sutent.
Additionally, 94% of patients in the combination arm experienced a reduction in tumor burden vs. 86% of patients in the Sutent arm.
A version of this story originally appeared on OncLive® as “Frontline Pembrolizumab/Axitinib Survival Benefit Upholds in Advanced RCC”.