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

Eur J Cancer. 2021 Mar:145:1-10. doi: 10.1016/j.ejca.2020.12.009. Epub 2021 Jan 4.

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.

Keywords: Axitinib; Long-term; Overall survival; Pembrolizumab; Progression-free survival; Renal-cell carcinoma; Safety.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Monoclonal, Humanized
  • Axitinib
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT02133742