1903P - Tumor response by baseline metastases in patients (pts) with renal cell carcinoma (RCC) treated with lenvatinib (L) plus pembrolizumab (P) vs sunitinib (S): Post hoc analysis of the CLEAR trial

Background

L+P is a standard of care (SoC) in 1L RCC based on significantly improved efficacy versus S in the CLEAR study [ Motzer 2021 ]. We report tumor response by baseline metastases at the final prespecified overall survival analysis timepoint (cutoff date: 31 Jul 22).

Methods

Treatment-naive adults with RCC were randomized to L (20 mg orally QD in 21-day cycles) plus P (200 mg IV Q3W) or L (18 mg orally QD in 21-day cycles) plus everolimus (5 mg orally QD in 21-day cycles) or S (50 mg orally QD; 4 wks on/2 wks off). This post hoc analysis examined response by baseline metastases in L+P (n=355) vs S (n=357) arms. Objective response rate (ORR), complete response (CR) rate, partial response (PR) rate, and progression-free survival (PFS) via independent imaging review (IIR) per RECIST v1.1 by baseline metastatic characteristics (site of metastasis [lung, lymph node, bone, liver, brain], number of metastatic sites [1 vs ≥2] and sums of diameters of target lesions [≥60 mm vs <60 mm]) are analyzed. Odds ratios (ORs) for ORR and hazard ratios (HRs) for PFS with 95% CIs are reported.

Results

The most common metastatic site by IIR at baseline was lung (L+P: 71.0%; S: 63.9%); 22.5% and 24.9% of pts, respectively, had bone metastases. 65.1% Of pts randomized to L+P and 66.1% of pts randomized to S had metastases at ≥2 sites. ORR favored L+P irrespective of metastatic site (Table). ORR favored L+P in pts with 1 (OR, 2.98 [95% CI 1.71, 5.21]) or ≥2 metastatic sites (OR, 5.06 [95% CI 3.40, 7.53]), and in pts with target lesion diameter sums ≥60 mm (OR, 10.50 [95% CI 6.08, 18.13]) or <60 mm (OR 3.14 [95% CI 1.94, 5.07]). PFS favored L+P vs S across subgroups (Table). CR and PR rates were higher in L+P vs S across subgroups (to be reported).

Conclusions

Tumor response favored L+P in all subgroups of interest, particularly in patients with increased burden of disease. Data further support L+P as a SoC in pts with 1L RCC.

Table: 1903P

^aIIR; ^bRECIST v1.1; ^cL+P n=6; S n=10.

Clinical trial identification

NCT02811861.

Editorial acknowledgement

Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

This study was sponsored by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

V. Gruenwald: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eisai, Ipsen, Janssen Cilag, Merck Serono, MSD, Pfizer, Roche, Novartis, Astellas; Financial Interests, Personal, Advisory Board: BMS, Eisai, Merck Serono, MSD, Nanobiotix, Pfizer, Roche, Apogepha, EUSA Pharm, Debiopharm, Oncorena, PCI Biotech; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: BMS, Novartis; Financial Interests, Institutional, Research Grant: Ipsen, MSD, Pfizer, BMS; Financial Interests, Personal and Institutional, Invited Speaker: Eisai, Ipsen; Financial Interests, Invited Speaker: PharmaMar; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology; Other, Other, Travel support to ESMO 2022 : Pfizer; Other, Other, Travel support for meeting: Merck Serono. R.R. McKay: Financial Interests, Personal, Advisory Board: AstraZeneca, Aveo, Bayer, BMS, Calithera, Dendreon, Exelixis, JNJ, Lilly, Merck, Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Telix, Tempus; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Non-Financial Interests, Trial Chair: AstraZeneca, Bayer; Non-Financial Interests, Steering Committee Member: Aveo, Eli Lilly, Merck; Non-Financial Interests, Local PI: BMS, Calibr, Eli Lilly, Genentech, JNJ, Merck, Oncternal, Poseida, Scholar Rock, SeaGen, Xencor; Non-Financial Interests, Institutional, Local PI: Exelixis. T. 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Keizman: Financial Interests, Personal, Invited Speaker: MSD, BMS, Pfizer, Astellas; Financial Interests, Personal, Advisory Board: MSD, BMS, Pfizer, Astellas, Eisai. C. Suarez Rodriguez: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, BMS (Inst), Ipsen, Pfizer S.L.U, Sanofi- Aventis, Hoffmann-La Roche LTD, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Astellas Pharma, BMS (Inst), Ipsen, Pfizer S.L.U, Hoffmann-La Roche LTD, Merck; Financial Interests, Institutional, Funding: Ipsen. S. Negrier: Financial Interests, Personal, Advisory Board: Pfizer, BMS, Ipsen, MSD, Eisai; Financial Interests, Institutional, Research Grant: Pfizer, Ipsen; Other, Other, Reimbursement of travel costs + Congress registration: Pfizer, Ipsen, MSD; Other, Other, Reimbursement of travel costs: BMS, Eisai. J. 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Motzer: Financial Interests, Institutional, Research Funding: BMS, Eisai, Exelixis, Genentech/Roche, Merck, Pfizer, Aveo Pharmaceuticals; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Aveo Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly, Merck, Novartis, Pfizer, Takeda. J. Burgents: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. C.E. Okpara: Financial Interests, Personal, Full or part-time Employment: Eisai. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. All other authors have declared no conflicts of interest.