Patients (n = 1,069) were randomized (1:1:1) to receive lenvatinib 20 mg PO QD + pembrolizumab 200 mg IV Q3W; lenvatinib 18 mg + everolimus 5 mg PO QD; or sunitinib 50 mg PO QD (4 weeks on/2 weeks off). The trial design for the CLEAR study is as follows:
HRQoL was assessed per FKSI-DRS, EORTC QLQ-C30, and EuroQoL EQ-5D-3L, at baseline, on day 1 of subsequent 3-week cycles starting with cycle 2, and at the off-treatment visit. HRQoL analyses (unless otherwise noted) were based on data from randomized patients with any HRQoL data who received ≥1 dose of study treatment. No adjustments for multiple testing or estimation were used; p-values and confidence intervals are nominal and descriptive.
For comparisons of lenvatinib + pembrolizumab versus sunitinib, overall changes from baseline at mean follow-up (week 46) favored lenvatinib + pembrolizumab with significant differences between treatments for physical functioning (least squares mean difference: 3.0, 95% CI 0.5, 5.5) and fatigue (least squares mean difference: −2.8, 95% CI −5.5, −0.1), dyspnea (least squares mean difference: −2.8, 95% CI −5.3, −0.3), and constipation (least squares mean difference: −2.2, 95% CI −4.2, −0.2). Least squares mean difference of the FKSI-DRS total score was 0.2 (95% CI −0.4, 0.7). A summary of these findings is as follows:
For comparisons of lenvatinib + everolimus versus sunitinib, overall changes from baseline at week 46 favored sunitinib with significant differences in overall HRQoL (least squares mean difference: −2.8, 95% CI −5.1, −0.5 assessed by the EORTC QLQ-C30 GHS/QoL scale) and pain (least squares mean difference: 2.8, 95% CI 0.1, 5.5), appetite loss (least squares mean difference: 4.2, 95% CI 1.3, 7.1), and diarrhea (least squares mean difference: 5.3, 95% CI 2.6, 7.9). Least squares mean difference of the FKSI-DRS total score was −0.4 (95% CI −1.0, 0.2). A summary of these findings is as follows:
14 of 18 scales for both lenvatinib + pembrolizumab and lenvatinib + everolimus versus sunitinib had no significant differences in least squares mean difference comparisons. The lenvatinib + pembrolizumab arm is favored over sunitinib for the median time to first deterioration for physical functioning, dyspnea, appetite loss, and EQ-5D VAS:
15 of 19 scales for both lenvatinib + pembrolizumab and lenvatinib + everolimus versus sunitinib had no significant differences in time to first deterioration comparisons.
Dr. Motzer concluded this presentation of the HRQoL findings from the CLEAR trial with the following conclusions:
- Lenvatinib + pembrolizumab demonstrated similarly or improved HRQoL and disease-related symptom scores supporting its tolerability compared with sunitinib
- Lenvatinib + everolimus resulted in similar or worse HRQoL and symptom scores compared with patients treated with sunitinib
- Efficacy, safety, and HRQoL results from the CLEAR trial support lenvatinib + pembrolizumab as first-line therapy for patients with advanced RCC
Clinical trial information: NCT02811861
Presented by: Robert J. Motzer, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
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