First-Line Lenvatinib Plus Pembrolizumab Yields Comparable in HRQOL Vs Sunitinib for Advanced RCC

Lenvatinib (Lenvima) plus pembrolizumab (Keytruda) and single-agent sunitinib (Sutent) yielded similar health-related quality of life (HRQOL) findings for patients with advanced renal cell carcinoma, according to results from the phase 3 CLEAR study (NCT02811861) published in The Lancet Oncology.

At baseline, the mean change in Functional Assessment of Cancer Therapy Kidney Symptoms Index-Disease-Related Symptoms (FKSI-DRS) was –1.75 (SE 0.59) compared with –2.19 (SE 0.66), –5.93 (SE, 0.86) vs –6.73 (SE, 0.94) for European Organisation for the Research and Treatment t of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and –4.96 (SE, 0.85) vs –6.64 (SE, 0.94) for the EQ-5D visual analog scale (VAS) in the combination and sunitinib groups, respectively.

Patients were randomized to receive either lenvatinib plus pembrolizumab (n = 355), lenvatinib plus everolimus (n = 357), or sunitinib (n = 357). The median follow-up for the HRQOL analyses was 12.9 months. HRQOL questionnaire was completed by 95% in the lenvatinib plus pembrolizumab group, 96% in the lenvatinib plus everolimus group, and 92% in the sunitinib group. Completion rates notably declined as patients discontinued treatment.

In the first arm, lenvatinib was administered at 20 mg per day in 21-day cycles and pembrolizumab was administered at 200 mg on day 1 of each 21-day cycle. In the second arm, lenvatinib was given at a starting dose at 18 mg per day and everolimus was given at 5 mg per day for each 21-day cycle. In the third arm, sunitinib was given at 50 mg per day for 4 weeks followed by 2 weeks off.

In the lenvatinib plus pembrolizumab group, the median duration of treatment was 17.0 months, 11.0 months in the lenvatinib plus everolimus group, and 7.8 months in the sunitinib group. Patients were permitted to stay on treatment beyond RECIST 1.1 defined disease progression if they were determined to be obtaining benefit with acceptable toxicity. This occurred in 23% of patients in the lenvatinib plus pembrolizumab group, 20% in the lenvatinib plus everolimus group, and 22% in the sunitinib group.

Completion of at least 1 HRQOL assessment after disease progression included 35% of patients in the lenvatinib plus pembrolizumab group, 38% in the Lenvatinib plus everolimus group, and 41% in the sunitinib group.

The lenvatinib plus pembrolizumab group was nominally significantly favored compared with the sunitinib group on 4 EORTC QLQ-C30 scales, including physical functioning, fatigue, dyspnea, and constipation. Treatment with sunitinib was not favored vs lenvatinib plus pembrolizumab for any scale (nominal P <.05).

The median time to first deterioration in the lenvatinib plus pembrolizumab group was 9.14 weeks (95% CI, 6.43-12.14) vs 12.14 weeks (95% CI, 9.14-15.29) in the sunitinib group (HR, 1.13; 95% CI, 0.94-1.35; log-rank P = .20) for FKSI-DRS, 12.00 weeks (95% CI, 7.29-15.14) vs 9.14 weeks (95% CI, 6.29-12.14; HR, 0.88; 95% CI, 0.74-1.05; log-rank P = .17) for EORTC QLQ-C30, and 9.43 weeks (95% CI, 6.43-12.29) vs 9.14 weeks (95% CI, 6.29-12.00; HR, 0.83; 95% CI, 0.70-0.99; log-rank P = .041) for ED-5D VAS, respectively.

The time to deterioration was nominally significantly favored in the lenvatinib plus pembrolizumab and sunitinib groups for EORTC QLQ-C30 in terms of physical functioning with a median of 15.29 weeks (95% CI, 12.29-21.43) vs 12.71 weeks (95% CI, 9.29-18.14; HR, 0.81; 95% CI, 0.68-0.98; log-rank P = .034). Similar favorability was observed with EORTC QLQ-C30 dyspnea time to first deterioration at a median of 39.29 weeks (95% CI, 24.43-51.00) in the lenvatinib plus pembrolizumab group vs21.14 weeks (15.43-32.71) in the sunitinib group (HR, 0.79; 95% CI, 0.64–0·97; log-rank P = .023). Finally, for EORTC QLQ-C30 appetite loss, the median time to first deterioration was 18.29 weeks (95% CI, 15.14-21.71) in the lenvatinib plus pembrolizumab group vs9.14 weeks (95% CI, 6.29-15.14) in the sunitinib group (HR, 0.82; 95% CI, 0.68-0.98; log-rank P = .028).

Reference

Motzer R, Porta C, Alekseev B, et al. Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study. Lancet Oncol. Published online April 27, 2022. doi:10.1016/S1470-2045(22)00212-1