(UroToday.com) As part of the “Game-changing Session 4” plenary session at the European Association of Urology (EAU) Virtual Annual Meeting, Dr. Bedke discussed health-related quality of life analysis from the KEYNOTE-426 trial. As most UroToday readers will know, the primary analysis of the KEYNOTE-426 trial demonstrated a significant survival advantage for patients with metastatic renal cell carcinoma who received pembrolizumab and axitinib as compared to those who received sunitinib.
Dr. Bedke began by highlighting the survival results from the first interim analysis of the KETNOTE-426 trial. As of this analysis, the combination use of pembrolizumab and axitinib demonstrated significant benefits in overall survival (hazard ratio 0.53, 95% confidence interval 0.37 to 0.74), in progression-free survival (hazard ratio 0.69, 95% confidence interval 0.57 to 0.84), and in objective response rate (59% vs 36%, p<0.001). In data presented at ASCO 2020, Dr. Plimack demonstrated that longer follow-up (median 30.6 months, minimum 23.4 months), pembrolizumab and axitinib continued to have significant benefit compared to sunitinib in terms of overall survival (hazard ratio 0.68, 95% confidence interval 0.55 to 0.85), progression free survival (hazard ratio 0.71, 95% confidence interval 0.60 t0 0.84), and objective response rate (60% vs. 40%).
Before moving to discuss the quality of life related data, Dr. Bedke reviewed the KEYNOTE-426 study design. This was a parallel group, phase III randomized controlled trial of patients with newly diagnosed or recurrent stage IV clear cell renal cell carcinoma who had not previously received systemic therapy and had measurable disease. Randomization was performed in a 1:1 fashion with stratification according to IMDC risk group (favourable vs. intermediate vs. poor) and geographic region (North American vs. Western Europe vs. rest of the world). For the purposes of the patient-reported outcome analyses, key endpoints included time to deterioration and change from baseline over time.
Assessing health related quality of life, the authors used a variety of instruments:
1. the QLQ-C30 which is a general measure to assess quality of life in cancer patients comparing one global health/quality of life score, 5 functioning states (physical, role, cognitive, emotional, and social) and 8 symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, and diarrhea).
2. the FKSI-DRS which measures 9 kidney-cancer specific cancer related symptoms including lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, and hematuria.
3. The EruoQol EQ-5D-3L VAS which measures the general state of health on a visual-analog scale across 5 domains of mobility, self-care, usual activities, pain/discomfort, and depression/anxiety.
Patient reported outcome assessment was performed frequently during the initial phases of treatment and somewhat less frequently as time went on. As highlighted in the figure below, the exact schedule differed somewhat for patients in the two arms but a comparable number of assessments was made.
In order to ensure reliability of the reported data, the authors assessed completion rates of the patient reported outcome measures as well as the compliance, with compliance defined as completion among those who are expected to complete the measures, excluding those who would be expected to be missing due to adverse events, death, treatment discontinuation, lack of availability of translated measures, and no visit scheduled.
As can be seen in the figure, fairly high rates of compliance were observed out to 30 weeks, with subsequent decreases. The primary analysis time point was 30 weeks. Assessment of time to deterioration was continued up to week 90.
Assessing their primary outcome of change from baseline over time, utilizing the QLQ-C30 measure of global health status, the authors found no evidence of a clinically important difference between the two study arms at any point during the 30 weeks examined.
Similar results were identified when using the EQ-5D-3L VAS and the KFSI-DRS scales. In analyses using each of these three measures, changes from baseline never met the threshold for minimally important differences.
Similarly, when the authors examined time to deterioration, either with confirmation (defined as the time to first onset of ≥7 point decrease from baseline with confirmation at the next visit) or without confirmation (same criteria but without the requirement for subsequent confirmation on the next visit), there were no differences between the treatment groups with a hazard ratio of 1.12 (95% confidence interval 0.91 to 1.38) in the confirmed analysis and 1.02 (95% confidence interval 0.86 to 1.20) in the unconfirmed analysis.
These data demonstrate that, despite receiving dual therapy with a tyrosine kinase inhibitor and immunotherapeutic checkpoint inhibitor, patients treated with pembrolizumab and axitinib has similar health related quality of life over 30 weeks as those receiving sunitinib monotherapy. When combined with the previously demonstrated benefits in oncologic endpoints, these data support the role of this treatment approach for first line treatment of patients with mRCC.
Presented by: Jens Bedke, MD, Professor and Chairman, Department of Urology Tuebingen, Tübingen, Germany
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, @WallisCJD on Twitter, at the Virtual 2020 EAU Annual Meeting #EAU20, July 17-19, 2020.
Read: ASCO 2020: KEYNOTE-426: Pembrolizumab plus Axitinib versus Sunitinib as First-Line Therapy for Advanced Renal Cell Carcinoma Watch: KEYNOTE-426: Pembrolizumab plus Axitinib versus Sunitinib as First-Line Therapy for Advanced Renal Cell Carcinoma (RCC) - Brian Rini