Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial Journal Article
| Authors: | Grünwald, V.; McKay, R. R.; Buchler, T.; Eto, M.; Park, S. H.; Takagi, T.; Zanetta, S.; Keizman, D.; Suárez, C.; Négrier, S.; Lee, J. L.; Santini, D.; Bedke, J.; Staehler, M.; Kollmannsberger, C.; Choueiri, T. K.; Motzer, R. J.; Burgents, J. E.; Xie, R.; Okpara, C. E.; Powles, T. |
| Article Title: | Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial |
| Abstract: | Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, ≥65% had two or more metastatic organs/sites involved, >80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions ≥60 mm. Lenvatinib plus pembrolizumab demonstrated greater progression-free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib-plus-pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard-of-care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites. © 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. |
| Keywords: | adult; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; major clinical study; overall survival; clinical trial; mortality; sunitinib; bone metastasis; cancer staging; lymph node metastasis; antineoplastic agent; metastasis; progression free survival; tumor volume; randomized controlled trial; antineoplastic combined chemotherapy protocols; pathology; risk factor; renal cell carcinoma; kidney neoplasms; monoclonal antibody; liver metastasis; lung metastasis; kidney tumor; carcinoma, renal cell; multicenter study; brain metastasis; neoplasm metastasis; phase 3 clinical trial; tumor growth; drug therapy; everolimus; personalized medicine; phylogeny; post hoc analysis; quinolines; quinoline derivative; clinical outcome; antibodies, monoclonal, humanized; phenylurea compounds; very elderly; lenvatinib; carbanilamide derivative; humans; human; male; female; article; pembrolizumab; lenvatinib plus pembrolizumab |
| Journal Title: | International Journal of Cancer |
| Volume: | 156 |
| Issue: | 7 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2025-04-01 |
| Start Page: | 1326 |
| End Page: | 1335 |
| Language: | English |
| DOI: | 10.1002/ijc.35288 |
| PUBMED: | 39739622 |
| PROVIDER: | scopus |
| PMCID: | PMC11789451 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
