Study 218: Higher Lenvatinib Starting Dose Trended Toward Better Outcomes

2021 Year in Review - Renal-Cell Carcinoma

Lenvatinib is a tyrosine kinase inhibitor that is approved for use in combination with the mammalian target of rapamycin inhibitor everolimus for patients with advanced renal-cell carcinoma who have been previously treated with antiangiogenic therapy. Lenvatinib is approved for use at a dose of 18 mg in combination with everolimus 5 mg. In the phase 2 Study 218, 2 starting doses of lenvatinib (14 mg [N = 156] and 18 mg [N = 155]) were compared in combination with everolimus. Those patients who started with the 14-mg dose were titrated to the 18-mg dose in the second cycle of treatment if they did not have intolerable grade 2 or any grade ≥3 adverse events. In the primary study analysis, the 14-mg starting dose of lenvatinib was shown to be noninferior to the 18-mg dose for objective response rate at 24 weeks.1

In an exploratory analysis of this trial, the efficacy of the 2 starting doses of lenvatinib was assessed by independent imaging review and, for patients previously treated with immune checkpoint inhibitor therapy, by an investigator.1

Independent imaging review–assessed objective response rate was similar for the 14-mg group (39.7%; 95% confidence interval [CI], 32.1%-47.4%) and the 18-mg group (38.7%; 95% CI, 31.0%-46.4%). Median independent imaging review–assessed progression-free survival was numerically longer with 18-mg lenvatinib (12.9 months; 95% CI, 9.2-17.1 months) than with 14-mg lenvatinib (11.0 months; 95% CI, 9.3-12.9 months) as was median overall survival (18 mg, median not evaluable [NE]; 95% CI, 23.8-NE; 14 mg, 27.0 months; 95% CI, 18.3-NE).1

Among the 82 patients who were previously treated with an immune checkpoint inhibitor, investigator-assessed objective response rate was 30.2% (95% CI, 17.2%-46.1%) in the 14-mg arm and 51.3% (95% CI, 34.8%-67.6%) in the 18-mg arm. In the 14-mg group, median progression-free survival was 12.0 months (8.9-16.7 months), and median overall survival was 17.1 months (10.6-NE). In the 18-mg group, median progression-free survival was 12.9 months (8.4-NE), and median overall survival was 18.0 months (13.1-NE). Similarly, in those patients who had not previously received immune checkpoint inhibitor therapy, efficacy outcomes favored the 18-mg group versus the 14-mg group.1

The safety profile was similar in the 14- and 18-mg treatment groups. Grade 3 or 4 treatment-emergent adverse events were reported in 71.7% of patients treated with the 14-mg lenvatinib starting dose and in 76.8% of patients treated with the 18-mg lenvatinib starting dose.1

The researchers concluded that the efficacy outcomes with the 18-mg starting dose of lenvatinib were numerically improved versus the 14-mg starting dose, and that improvement was independent of previous receipt of immune checkpoint inhibition.1


  1. Pal SK, Puente J, Chin Heng DY, 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(6_suppl):Abstract 307.

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