ASCO GU 2022: Real-World Treatment Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States

( The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Yousef Zakharia and colleagues presenting real-world treatment outcomes of first-line axitinib plus pembrolizumab in patients with advanced RCC in the United States. The combination of axitinib plus pembrolizumab is a standard of care in the first-line treatment of patients with advanced clear cell RCC based on the phase 3 KEYNOTE-426 trial.1-2 In extended follow-up of the KEYNOTE-426 phase 3 trial, approximately 1/5 of patients who received axitinib plus pembrolizumab discontinued axitinib treatment secondary to treatment-related adverse events and nearly 2/3 had treatment interruption. This analysis describes the demographic and clinical characteristics, treatment and outcomes of patients receiving first-line axitinib plus pembrolizumab in a real-world setting.

Medical record data were extracted from the Flatiron Health Database, which includes ~280 cancer clinics across 800 sites in the United States. Eligible patients had confirmed Stage IV or metastatic RCC and initiated first-line axitinib plus pembrolizumab on or after January 1, 2018 to March 31, 2021. Tumor response is reported as best overall response to first-line therapy. Real-world progression-free survival and overall survival are reported as patients without a clinical event (real-world progression-free survival: progression/death; real-world overall survival: death) at landmark time periods (3, 6, 9, and 12 months).

There were 355 patients that received first-line axitinib plus pembrolizumab, with follow-up of 9.7 (0.1–24.3) months. Most patients were male (69.6%), and the median age was 68.0 (IQR 60.0–75.0) years. At diagnosis, 55.5% of patients had Stage IV RCC and 77.2% of patients had clear cell histology. IMDC Risk Score was favorable, intermediate, and poor in 27 (7.6%), 126 (35.5%), and 76 (24.4%) patients, respectively. Real-world progression-free survival at 3 months and 1 year was achieved by 77% and 39% of patients, respectively. Real-world overall survival ranged from 91% surviving at 3 months to 74% of patients surviving at 1 year. The following table summarizes patients experiencing clinical events during follow-up at specified landmark time points: 

ASCO GU 2022_Zakharia_0 

 The best overall response rate to first-line was 47.9%, complete response was observed in 4.2% and partial response was observed in 46.2%:

ASCO GU 2022_Zakharia_1 

At the time of analysis, 270 patients (76%) received only first-line therapy with axitinib plus pembrolizumab, while 85 patients (24%) received ≥1 subsequent line of treatment. VEGF-receptor inhibitors were the most commonly used second-line treatment (51 patients, 60%), with cabozantinib as the most frequently used VEGF-receptor inhibitor (40 patients, 47%). The following figure summarizes subsequent events following therapy management due to toxicity: 

ASCO GU 2022_Zakharia_2 

Dr. Zakharia concluded this presentation of real-world treatment outcomes of first-line axitinib plus pembrolizumab with the following take-home messages:

  • This study provides real-world evidence for the use and effectiveness of first-line axitinib plus pembrolizumab in patients with advanced RCC, which was comparable to the randomized trials
  • Axitinib plus pembrolizumab was used across all IMDC risk groups
  • Dose holds and changes may represent effective strategies to manage toxicity
  • A relatively small proportion of patients who discontinued axitinib plus pembrolizumab due to treatment-related toxicity switched to another treatment
  • While these initial finding support the use of axitinib plus pembrolizumab, additional follow-up is warranted to provide further understanding of the clinical outcomes and treatment patterns of patients with advanced RCC in the US receiving first-line axitinib plus pembrolizumab


Presented By: Yousef Zakharia, MD, University of Iowa, Iowa City, IA

Co-Authors: Despina Thomaidou, Benjamin Li, Gordan Siu, Rebecca Levin, Anna Vlahiotis, Giovanni Zanotti
Affiliations: University of Iowa, Iowa City, IA, Pfizer Inc, Hellas, Greece, Pfizer Inc, New York, NY

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022


  1. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 2019;380(12):1116-1127.
  2. Powles T, Plimack ER, Soulieres D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomized, open-label, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1563-1573.

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