Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial.

Abstract

BACKGROUND:

Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).

METHODS:

Fifty-two treatment-naïve patients with advanced RCC were treated with oral axitinib 5 mg twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of response (DoR) and OS were summarised using the Kaplan-Meier method.

RESULTS:

At a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), median OS was not reached; 38 (73.1%) patients were alive. The probability of being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no treatment-related deaths.

CONCLUSIONS:

In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.

• Authors: Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Jamal C Tarazi, William Duggan, Rodolfo Perini, Mahgull Thakur, Kathrine C Fernandez, Toni K Choueiri
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 145 Pg. 1-10 (03 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 33412465 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Axitinib
• pembrolizumab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Axitinib (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, mortality, pathology)
• Female
• Humans
• Kidney Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Progression-Free Survival
• Time Factors
• United States