KEYNOTE-426: no QoL differences pembrolizumab + axitinib versus sunitinib

The open-label, phase 3 KEYNOTE-426 trial demonstrated a significant survival advantage for patients with metastatic renal-cell carcinoma (mRCC) across all risk groups who received pembrolizumab with axitinib compared with those who received sunitinib. Prof. Jens Bedke (University of Tübingen, Germany) presented results of the patient-reported outcome analyses in which no evidence was found of a clinically important difference in quality of life (QoL) between the 2 study arms at any point during the 30 weeks of examination [1].

With a median follow-up of 30.6 months, KEYNOTE-426 demonstrated that pembrolizumab and axitinib (n=432) had a significant benefit compared with sunitinib (n=429) in mRCC patients in terms of overall survival (HR 0.68; 95% CI 0.55-0.85), progression-free survival (HR 0.71; 95% CI 0.60-0.84), and objective response rate (60% vs 40%). Key endpoints regarding the patient-reported outcome analyses included time to deterioration and change from baseline over time. The primary analysis timepoint was 30 weeks. Assessment of time to deterioration was continued up to week 90.

The patient-reported outcome assessment was performed with the following instruments, although arm-specific adjustments to the treatment protocol changed the scheduling between the arms:

1. 
   
   1. QLQ-C30: general QoL in cancer patients;
   2. FKSI-DRS: 9 kidney cancer-specific cancer-related symptoms; and
   3. EQ-5D-3L VAS: general state of health.

The primary outcome –change from baseline over time– never met the threshold for minimally important differences between the 2 study arms at any point during the 30 weeks examined, with any of the validated instruments. Thus, the researchers concluded that health-related QoL in patients treated with the combination pembrolizumab and axitinib was similar to those receiving sunitinib monotherapy. There were also no differences between the treatment groups in time to deterioration in the confirmed analysis (HR 1.12; 95% CI 0.91-1.38), as well as in the unconfirmed analysis (HR 1.02; 95% CI 0.86-1.20).

1. 
   
   1. Bedke J, et al. EAU20 Virtual Congress, 17-26 July 2020, Game-changing Session 4.

Posted on 20 August 202029 February 2024