Patients with advanced RCC and no prior systemic therapy 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). Randomization was stratified by geographic region and MSKCC prognostic group. The trial schema for the CLEAR trial is as follows:
In this descriptive follow-up analysis, with a data cutoff of March 31, 2021, they reported updated PFS, ORR, and DOR, by independent imaging review per RECIST v1.1 for lenvatinib + pembrolizumab and sunitinib, and an exploratory analysis of patients who completed 2 years of pembrolizumab and continued lenvatinib.
The median survival follow-up was 33.7 and 33.4 months for patients randomized to lenvatinib + pembrolizumab (n = 355) and sunitinib (n = 357), respectively. The median PFS was 23.3 months (95% CI 20.8-27.7) in the lenvatinib + pembrolizumab arm and 9.2 months (95% CI 6.0-11.0) in the sunitinib arm (HR 0.42, 95% CI 0.34-0.52):
PFS favored lenvatinib + pembrolizumab versus sunitinib treatment regardless of MSKCC or IMDC risk group:
The median OS was not reached in either arm: lenvatinib + pembrolizumab 95% CI 41.5 – NE versus sunitinib 95% CI 38.4 – NE (HR 0.72, 95% CI 0.55-0.93):
Objective response rate was 71.0% (95% CI 66.3-75.7) with lenvatinib + pembrolizumab and 36.1% (95% CI 31.2-41.1) with sunitinib (relative risk: 1.97, 95% CI 1.69-2.29). Among patients who completed 2 years of pembrolizumab (n = 101), most (n = 65) had IMDC intermediate/poor risk and fewer (n = 36) had favorable risk disease, consistent with the intention-to-treat population. Pembrolizumab completers had a 36-month OS rate of 94.5%:
Overall, 69 (68.3%) of these patients had treatment-related treatment-emergent adverse events.
Dr. Porta concluded his presentation by discussing the updated efficacy of lenvatinib + pembrolizumab versus sunitinib in patients with advanced RCC in the CLEAR study with the following take-home messages:
- With this longer follow-up, lenvatinib + pembrolizumab continued to show a clinically meaningful benefit versus sunitinib, consistent with prior results of the CLEAR study
- A large proportion of patients treated with lenvatinib + pembrolizumab completed 2 years of pembrolizumab and continued with lenvatinib monotherapy with ongoing clinical benefit
- These data show that the efficacy benefit observed at the primary analysis was robust and maintained with further follow-up, supported by lenvatinib + pembrolizumab as a standard of care for first-line advanced RCC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA
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