(UroToday.com) KEYNOTE-426 was a large phase III clinical trial that randomly assigned 861 patients with clear cell (renal cell carcinoma) RCC to either pembrolizumab + axitinib (5 mg BID) or sunitinib (50 mg daily x 4 weeks, 6-week cycle). This data, initially presented at GU ASCO 2019, showed that combination pembrolizumab plus axitinib significantly improved overall survival at 1 year (90% vs 78%, HR 0.53) and objective response rates was 59% with pembro/axi compared with 36% with sunitinib. The benefit of pembro/axi was observed across all IMDC risk groups, regardless of PD-L1 expression. This presentation provides updated data from Keynote-426.
This presentation at ASCO 2020 provides data with a minimum follow up of 23 months on Keynote-426. The study schema is shown above. During the first data cutoff, a minimum of 7 months was required and at that time, the study met both primary endpoints of improving overall survival and PFS.
22% of patients are still on treatment in the pembro/axi arm compared with 17.9% in the sunitinib arm. For patients who discontinued treatment on trial, 54.5% of patients on pembro/axi received subsequent therapy, the majority of patients being a VEGF/VEGFR inhibitor and 69.3% of patients on the sunitinib arm.
Updated overall survival analysis shows that 74% of patients are alive from the pembro/axi arm at 24 months, compared with 66% of patients on sunitinib arm. Median survival is not yet reached with pembro/axi and was 35.7 months with sunitinib.
In terms of progression-free survival, median PFS in the pembro/axi arm was 15.4 months and 11.1 months with sunitinib, HR 0.71. The objective response held at 60.2% with pembro/axi and was 40% in the sunitinib arm. The median duration of response on pembro/axi was 23.5 months compared with 15.9 months with sunitinib.
For patients with favorable-risk disease, there was no significant difference in OS or PFS, with a median PFS of 20.8 months with pembro/axi and 18 months with sunitinib. However, for patients with IMDC intermediate or poor risk disease, there were significant differences in OS and PFS with HR of 0.63 for OS and 0.69 for PFS.
No new safety signals emerged with prolonged follow up. 66% of patients on pembro/axi had grade 3-5 toxicity compared with 62.4% of patients on sunitinib. Hypertension, diarrhea, and hypothyroidism were common in both arms. Patients on sunitinib had more thrombocytopenia and neutropenia and patients on pembro/axi had more dysphonia and immune-related side effects like hypothyroidism and pneumonitis.
94% of patients on pembro/axi had some reduction in tumor burden compared with 86% of patients on sunitinib. A post-hoc depth of response and overall survival analysis was completed all patients who were alive at 6 months. Patients were divided in subgroups based on tumor reduction in size. For patients with a complete response in either arm, there were very few deaths in the following 42 months. However, for patients with near CR, 80% to almost 100% shrinkage, patients on pembro-axitinib continued to do almost just as well as the CR arm, whereas patients receiving sunitinib did less well with an OS between 70-80%.
These data presented today continue to show that pembro/axi is superior to sunitinib for most patients with mRCC and landmark analyses show that the depth of tumor shrinkage correlates with overall survival. It will be interesting to follow the OS and PFS curves for patients in the IMDC favorable risk category to see if they separate out any further with longer follow up.
Presented by: Elizabeth R. Plimack, MD, MS, Chief, Division of Genitourinary Medical Oncology, Professor, Department of Hematology/Oncology, Director, Genitourinary Clinical Research, Kidney, Bladder, and Prostate Cancer TRDG Member, NCCN, Bladder/Penile Cancers Panel Member, NCCN, Kidney Cancer Panel Member, NCCN, Prostate Cancer Panel Member, Fox Chase Cancer Center
Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020
Watch: KEYNOTE-426: Pembrolizumab plus Axitinib versus Sunitinib as First-Line Therapy for Advanced Renal Cell Carcinoma (RCC) - Brian Rini