Adjuvant pembrolizumab (Keytruda) extended disease-free survival (DFS) in patients with renal cell carcinoma (RCC), according to findings from the phase 3 KEYNOTE-564 trial announced today by Merck (MSD), the developer of the PD-1 inhibitor.1
An independent data panel determined during an interim analysis that, as compared with placebo, single-agent pembrolizumab achieved the trial’s primary end point by inducing a statistically significant and clinically meaningfully DFS improvement. The trial remains ongoing to evaluate the key secondary end point of overall survival (OS).
According to Merck, no new safety signals emerged as compared with previously reported trials of pembrolizumab. The company plans to present the actual data from the study at a future medical conference.
“Since its first approval in renal cell carcinoma nearly 2 years ago, Keytruda has become an important first-line treatment option in combination with axitinib for patients with advanced renal cell carcinoma,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, stated in a press release.
“These new data are the result of our research to evaluate the role of Keytruda in helping patients with earlier stages of disease and are the first positive results for an anti-PD-1 therapy in the adjuvant treatment of patients with renal cell carcinoma. We look forward to sharing results of KEYNOTE-564 with the medical community and regulatory authorities as soon as possible,” added Baynes.
The parallel assignment, double-blind phase 3 KEYNOTE-564 trial (NCT03142334) included patients with RCC with a clear cell component who had undergone nephrectomy and had intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED). Patients were not eligible to enroll if they had prior radiotherapy for RCC, or brain or bone metastatic lesions.
Pembrolizumab is currently approved by the FDA for use in combination with axitinib as a frontline treatment for patients with advanced RCC.2 The approval was based on the phase 3 KEYNOTE‑426 trial (NCT02853331).
The data from KEYNOTE‑426 evaluated by the FDA showed that pembrolizumab/axitinib reduced the risk of death by 47% versus sunitinib in the frontline setting (HR, 0.53; P <.0001). The 12-month OS rates were 90% versus 78% with the combination versus sunitinib, respectively. The median OS was not reached in either group of patients. The combination also led to significant improvement in progression-free survival (PFS), with a median PFS of 15.1 months versus 11.1 months with sunitinib (HR, 0.69; P = .0001).
Also in the frontline RCC setting, it was reported earlier this year at the 2021 Genitourinary Cancers Symposium that pembrolizumab plus lenvatinib (Lenvima) reduced the risk of death by 34% versus sunitinib in the phase 3 CLEAR trial.3 The median OS was not reached in either arm. The combination also significantly improved PFS versus sunitinib, with a median PFS of 23.9 months versus 9.2 months, respectively (HR, 0.39; P <.001).
Based on the findings from the CLEAR trial, the National Comprehensive Cancer Network added pembrolizumab/lenvatinib to its clinical guidelines as a Category 1 recommendation for the frontline treatment of patients with advanced RCC.4
1. Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Superior Disease-Free Survival (DFS) Compared With Placebo as Adjuvant Therapy in Patients With Renal Cell Carcinoma (RCC) Following Surgery. Published online April 8, 2020. Accessed April 8, 2020. https://bit.ly/3dREIAO.
2. FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma. Published online April 19, 2019. Accessed April 8, 2020. https://bit.ly/39VMW9D.
3. Motzer RJ, Porta C, Eto M, et al. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study). J Clin Oncol. 2021; 39(suppl6):269. doi: 10.1200/JCO.2021.39.6_suppl.269
4. National Comprehensive Cancer Network. Kidney Cancer. Version 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf