ASCO 2024: Lenvatinib plus Pembrolizumab vs Sunitinib in Advanced Renal Cell Carcinoma: Patterns of Progression and Subsequent Therapy in the CLEAR Trial

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31^st and June 4^th, 2024 was host to a kidney and bladder cancers poster session. Dr. Viktor Grünwald presented a follow-up analysis of progression and subsequent therapy patterns from the CLEAR trial of lenvatinib plus pembrolizumab versus sunitinib in advanced clear cell renal cell carcinoma (ccRCC).

In the primary analysis of the phase 3 CLEAR trial, the combination of lenvatinib plus pembrolizumab resulted in statistically significant and clinically meaningful improvements in overall survival compared with sunitinib for patients with advanced renal cell carcinoma.¹ These results were further confirmed at the final pre-specified overall survival analysis (Figure 1).²
In this report, Dr. Grünwald presented the patterns of progression and subsequent therapy from the CLEAR trial.

The eligibility criteria and dosage information for CLEAR are summarized in the figure above. The objective of this analysis was to evaluate progression patterns within individual organs, with time to progression defined for each organ independently using lesions within each specific organ only, based on independent imaging review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Within each organ, progressive disease was defined as a 20% increase in the sum of diameters of target lesion(s) in that organ, progression of non-target lesion(s) in that organ, and/or any new lesion(s) in that organ. Medians were estimated using the Kaplan–Meier method, and 95% confidence intervals were estimated using a generalized Brookmeyer and Crowley method. Hazard ratios (HRs) for lenvatinib plus pembrolizumab versus sunitinib were calculated using Cox regression modeling with treatment as a factor. The Efron method was used for correction of tied events.

In the lenvatinib plus pembrolizumab arm (n = 355), 252 (71%) patients had lung metastases, 162 (46%) patients had lymph node metastases, 80 (23%) patients had bone metastases, and

63 (18%) patients had liver metastases at baseline. Correspondingly, in the sunitinib arm (n = 357), 228 (64%) patients had lung metastases, 156 (44%) had lymph node metastases, 89 (25%) patients had bone metastases, and 70 (20%) patients had liver metastases at baseline. The number of patients with a baseline brain metastasis across treatment arms was very low (≤ 10). The HRs for time to disease progression favored lenvatinib plus pembrolizumab versus sunitinib treatment across tumors in different organs (bone, central nervous system, kidney, liver, lung, and lymph nodes; Figure 2–7).
At the time of overall disease progression, the median decreases in percent changes in sums of diameters of target lesions were greater with lenvatinib plus pembrolizumab versus sunitinib treatment (−48.1% vs −17.4%; Figure 8).
In the lenvatinib plus pembrolizumab arm, 181 patients received subsequent anti-cancer regimens during survival follow up:

43 patients received axitinib
101 received cabozantinib
42 received nivolumab

In the sunitinib arm, 246 patients received subsequent anticancer regimens:

47 patients received axitinib
107 received cabozantinib
175 received nivolumab

Patients in the lenvatinib plus pembrolizumab arm continued with second-line axitinib or cabozantinib treatment longer than those in the sunitinib arm (Table 1).

Dr. Grünwald concluded as follows:

In all assessed organs, the time to tumor progression was prolonged with lenvatinib plus pembrolizumab versus sunitinib treatment
At the time of overall disease progression, the median tumor burden of target lesions was lower with lenvatinib plus pembrolizumab versus sunitinib treatment.
Patients in the lenvatinib plus pembrolizumab arm remained on second line axitinib or cabozantinib treatment longer compared to patients in the sunitinib arm.
Together, these results continue to support lenvatinib plus pembrolizumab treatment as a standard-of-care first-line therapy in patients with advanced ccRCC.

Presented by: Viktor Grünwald, MD, PhD, Professor, Interdisciplinary Genitourinary Oncology, University Hospital Essen, Essen, Germany

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, May 31^st – June 4^th, 2024

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