Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma Journal Article
| Authors: | Lee, C. H.; Motzer, R. J.; Glen, H.; Michaelson, M. D.; Larkin, J.; Minoshima, Y.; Kanekiyo, M.; Ikezawa, H.; Sachdev, P.; Dutcus, C. E.; Funahashi, Y.; Voss, M. H. |
| Article Title: | Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma |
| Abstract: | Background: No biomarkers have been established to predict treatment efficacy in renal cell carcinoma (RCC). In an exploratory retrospective analysis of a Phase 2 study, we constructed composite biomarker scores (CBSs) to predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic RCC randomised to receive lenvatinib-plus-everolimus. Methods: Of 40 biomarkers tested, the 5 most strongly associated with PFS (HGF, MIG, IL-18BP, IL-18, ANG-2) or OS (TIMP-1, M-CSF, IL-18BP, ANG-2, VEGF) were used to make a 5-factor PFS-CBS or OS-CBS, respectively. A 2-factor CBS was generated with biomarkers common to PFS-CBS and OS-CBS. Patients were divided into groups accordingly (5-factor-CBS high: 3−5, CBS-low: 0–2; 2-factor-CBS high: 1–2, CBS-low: 0). Results: PFS/OS with lenvatinib-plus-everolimus were significantly longer in the 5-factor CBS-high group versus the CBS-low group (P = 0.0022/P < 0.0001, respectively). In the CBS-high group, PFS/OS were significantly longer with lenvatinib-plus-everolimus versus everolimus (P < 0.001/P = 0.0079, respectively); PFS was also significantly longer with lenvatinib-plus-everolimus versus lenvatinib (P = 0.0046). The 5-factor-CBS had a predictive role in PFS and OS after multivariate analysis. Similar trends were observed with the 2-factor-CBS for PFS (i.e., lenvatinib-plus-everolimus versus everolimus). Conclusions: The 5-factor CBS may identify patients with metastatic RCC who would benefit from lenvatinib-plus-everolimus versus everolimus; additional validation is required. Clinical trial registration: The clinical trial registration number is NCT01136733. © 2020, The Author(s). |
| Keywords: | vasculotropin; vasculotropin receptor 3; adult; cancer survival; controlled study; aged; major clinical study; overall survival; monotherapy; progression free survival; multiple cycle treatment; vasculotropin receptor 2; retrospective study; tumor marker; vasculotropin d; correlation analysis; angiopoietin receptor; kidney metastasis; everolimus; intercellular adhesion molecule 1; predictive value; colony stimulating factor 1; angiopoietin 2; tissue inhibitor of metalloproteinase 1; interleukin 18; cxcl9 chemokine; randomized controlled trial (topic); phase 2 clinical trial (topic); clinical outcome; exploratory research; multicenter study (topic); combination drug therapy; lenvatinib; intention to treat analysis; human; male; female; priority journal; article; fibroblast growth factor 21; interleukin 18 binding protein |
| Journal Title: | British Journal of Cancer |
| Volume: | 124 |
| Issue: | 1 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-01-05 |
| Start Page: | 237 |
| End Page: | 246 |
| Language: | English |
| DOI: | 10.1038/s41416-020-01092-0 |
| PUBMED: | 33024271 |
| PROVIDER: | scopus |
| PMCID: | PMC7782770 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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