There was no benefit with modified dosing of lenvatinib plus everolimus compared with standard dosing, given the similar safety and a numerical efficacy benefit of the standard regimen, for patients with previously treated advanced renal cell carcinoma (RCC), according to a presentation at the 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020).
Lenvatinib plus everolimus is a currently approved regimen for the second-line treatment of advanced RCC, after progression on an antiangiogenic therapy. However, a majority of patients require dose interruptions or reductions with this regimen, and the treatment discontinuation rate is 29%.
The purpose of this trial was to evaluate modified dosing of lenvatinib plus everolimus and “see if we can get around this hurdle,” Sumanta K. Pal, MD, of the City of Hope Cancer Center in Duarte, California, and presenter of the study, said.
The phase 2 trial randomly assigned 343 patients with previously treated clear cell RCC to receive the approved dose of 18 mg of lenvatinib plus 5 mg of everolimus or the modified dose of 14 mg of lenvatinib plus 5 mg of everolimus. In the modified-dose arm, if patients tolerated therapy for the first 4 weeks, then the lenvatinib dose was escalated to 18 mg.
The coprimary endpoints were objective response rate (ORR) at 24 weeks and safety. Secondary endpoints included overall ORR, progression-free survival (PFS), overall survival (OS), and treatment discontinuations.
At baseline, the median patient age was 62 years, and 74.9% of patients were male. The majority of patients were at intermediate risk (53.4%), followed by favorable risk (28.9%), and poor risk (17.8%). A majority of patients had undergone a prior nephrectomy, and approximately one-quarter had received an anti–programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) treatment.
The ORR at 24 weeks was 32.1% in the modified-dose arm compared with 34.8% in the standard-dose arm (odds ratio [OR], 0.88; 95% CI, 0.59-1.23; P =.2676), indicating that the standard dose was noninferior to the modified dose. The overall ORR was also not significantly different at 34.6% with the modified dose and 40.6% with the standard dose (OR, 0.77; 95% CI, 0.52-1.14). The median duration of response was 11.5 months and 11.7 months, respectively.
The median PFS was longer with the standard dose at 14.7 months compared with 11.1 months with the modified dose. Median OS was not yet evaluable with the standard dose and was 27 months with the modified dose.
Tolerability was similar between the arms, with 82.8% of patients in the modified arm experiencing an intolerable grade 2 event or any grade 3 or more adverse events (AEs) compared with 79.6% in the standard dose arm (P =.4763). Dose reduction of lenvatinib occurred in 64.7% of patients in the modified-dosing arm compared with 65.5% of patients in the standard-dosing arm.
Treatment-emergent AEs (TEAEs) that led to study drug discontinuation occurred in 32.4% of patients in the modified-dose arm compared with 26.8% of patients in the standard-dose arm. Dose interruption occurred in 74.6% and 83.3% patients, respectively, and dose reduction occurred in 67.6% and 69.6% of patients, respectively.
Dr Pal concluded that “these data really support the current dosing regimen of lenvatinib at 18 mg per day with everolimus at 5 mg per day.” He noted that there was no difference in safety, and although the doses were noninferior to each other, there was a numerical benefit with the standard dose.
Disclosures: Funding for the research discussed in this summary was provided by Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Pal SK, Puente J, Heng DYC, et al. Phase 2 trial of lenvatinib at 2 starting doses + everolimus in renal cell carcinoma (RCC). Presented at: 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020); November 6-7, 2020. Abstract CTR142.
This article originally appeared on Cancer Therapy Advisor