Higher Lenvatinib Dose May Improve HRQoL in RCC

The standard dose of lenvatinib (Lenvima), 18 mg per day, demonstrated an improved health-related quality of life (HRQoL) and a longer time to deterioration over a lower starting dose of lenvatinib, 14 mg per day, in patients with renal cell carcinoma (RCC), according to secondary results from a phase 2 trial (NCT03173560).1

“Based on these findings, patients who received lenvatinib 18 mg starting dose had better quality of life and less severe symptoms than those who received lenvatinib 14 mg starting dose,” said Cristiane Decat Bergerot, PhD, MS, BS, a postdoctoral fellow at City of Hope National Medical Center in Duarte, California, during the virtual poster presentation at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium. “In addition, participants who received lenvatinib 18 mg maintained quality of life and symptom control for longer than those who received lenvatinib 14 mg starting dose.”

In this phase 2, randomized, open-label trial, researchers compared the safety and efficacy of 2 different starting doses of lenvatinib—18 mg per day (n = 172; median age, 61 years; 77% men) or 14 mg per day (n = 171; median age, 62 years; 75% men)—in patients with renal cell carcinoma who previously received 1 VEGF-targeted treatment. Both starting doses of lenvatinib were given in combination with 5 mg of everolimus per day. Patients received treatment until unacceptable toxicity, disease progression, withdrawal of consent, or the end of the study.

In the primary analysis of the trial, minimal difference was observed between the 2 doses of lenvatinib in terms of objective response rate (ORR) at 24 weeks at 39.1% with the 14-mg dose and 34.8% with the 18-mg dose (odds ratio, 1.20; 90% CI, 0.82-1.76) by independent review. The overall ORR by independent review was 39.7% versus 38.7%, respectively. The median progression-free survival was 12.0 months in the 14-mg group versus 12.9 months in the 18-mg group (HR, 1.27; 90% CI, 0.74-2.20).2

Researchers used 3 different instruments to measure HRQoL: Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS), EQ-5D-3L, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Quality-of-life scores were measured at baseline, first day of the first cycle of treatment and at the end-of-treatment visit.1

Average quality-of-life scores in patients assigned the 18-mg dose were higher compared with those assigned the 14-mg dose. In addition, the higher dose group had lower symptom severity compared with the lower dose group.

“Mean differences in favor of lenvatinib 18 mg were seen in most scales,” said Bergerot during the presentation. “However, none of these differences exceeded the minimally important difference for clinical significance.”

The median time to first deterioration was longer in patients assigned the 18-mg starting dose compared with those assigned the 14-mg starting dose in most scales including the FKSI-DRS total score (HR, 1.3; 12 vs 15.71 weeks, respectively). This was also observed for EORTC QLQ-C30, which assessed emotional functioning (HR, 1.35; 20.71 vs 34.86 weeks), social functioning (HR, 1.32; 12.14 vs 16.29 weeks), dyspnea (HR, 1.54; 20.29 vs 40.29 weeks), insomnia (HR, 1.45; 15.43 vs 28.14 weeks), and financial difficulties (HR, 1.59; 36.14 vs not estimable).

Patients assigned the 18-mg starting dose also had a longer time to definitive deterioration based on the FKSI-DRS total score compared with those assigned to the 14-mg starting dose (HR, 1.46; 56.43 vs 80.14 weeks, respectively). This was also observed for EORTC QLQ-C30 scores, which assessed factors such as quality of life/global health status (HR, 1.44; 46.43 vs 84.71 weeks), physical functioning (HR, 1.65; 56.14 vs 99.57 weeks), cognitive functioning (HR, 1.44; 56.14 vs 72.29 weeks), and fatigue (HR, 1.59; 40.14 vs 72.29 weeks).

“In conclusion, these findings support the approved treatment of lenvatinib 18-mg starting dose in combination with everolimus as an effective treatment option for patients with renal cell carcinoma following one prior VEGF-targeted treatment while maintaining quality of life,” said Bergerot during the presentation. However, in the poster, the researchers cautioned that there were no statistical hypotheses prespecified based on the HRQoL data, so the results were to be taken as descriptive only.

_References

_{1. Bergerot CD, Rha SY, Pal SK, et al. Health-related quality-of-life outcomes from a phase II open-label trial of two different starting doses of lenvatinib in combination with everolimus for treatment of renal cell carcinoma following one prior VEGF-targeted treatment. J Clin Oncol. 2021;39(suppl 6):314. doi:10.1200/JCO.39.6_suppl.314}

_{2. Pal SK, Puente J, Yick Chin Heng D, et al. Phase II trial of lenvatinib (LEN) at two starting doses + everolimus (EVE) in patients (pts) with renal cell carcinoma (RCC): Results by independent imaging review (IIR) and prior immune checkpoint inhibition (ICI). J Clin Oncol. 2021;39(suppl 6):307. doi:10.1200/JCO.2021.39.6_suppl.306}