Randomized phase II, three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in patients (pts) with metastatic renal cell carcinoma (mRCC).

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 4506)
Robert Motzer, Thomas Hutson, Hilary Glen, Dror Michaelson, Ana M. Molina, Timothy Eisen, Jacek Jassem, Jakub Zolnierek, Pablo Maroto, Begona Mellado, Bohuslav Melichar, Jiri Tomasek, Han-Joo Kim, Karen Wood, Corina Dutcus, James M. G. Larkin; Memorial Sloan Kettering Cancer Center, New York, NY; Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Massachusetts General Hospital Cancer Center, Boston, MA; Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY; Addenbrooke's Hospital, Cambridge, United Kingdom; Medical University, Gdansk, Poland; Centrum Onkologii, Instytut w Warszawie, Warsaw, Poland; Departamento de Oncología Médica, Barcelona, Spain; Translational Genomics and Targeted Therapeutics in Oncology.IDIBAPS. Medical Oncology Department. Hospital Clinic, Barcelona, Spain; Onkologicka Klinika, Lekarska Fakulta Univerzity Palackeho a Fakultni Nemocnice, Olomouc, Czech Republic; Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic; Eisai Inc., Woodcliff Lake, NJ; Eisai Ltd., Hatfield, United Kingdom; Royal Marsden NHS Hospital, London, United Kingdom

Abstract Disclosures


Background: Lenvatinib (LEN), an oral tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, in combination with EVE had manageable toxicity and antitumor activity in a phase 1 mRCC trial (CCP 2013;73:181). This phase II, open-label, multicenter study compared LEN, EVE, and LEN+EVE in pts with mRCC. Methods: Pts with progressive clear cell mRCC following 1 VEGF-targeted therapy were randomized 1:1:1 to LEN (24 mg/d), EVE (10 mg/d), or LEN+EVE (18+5 mg/d) in 28d cycles. The primary objective was progression-free survival (PFS) of LEN+EVE or LEN vs EVE. Secondary objectives included overall survival (OS), objective response rate (ORR), and safety. Primary analysis data cutoff was June 13, 2014. Results: One hundred and fifty-three pts were enrolled: 99% had one prior VEGF-targeted therapy, 1% had two; 18% had prior immunotherapy. LEN+EVE prolonged PFS vs EVE (Table; hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.24–0.68; P < 0.001). LEN alone also prolonged PFS vs EVE (HR 0.61; 95% CI 0.38–0.98; P = 0.048). LEN+EVE and LEN improved ORR vs EVE (P < 0.001 and P = 0.007, respectively). Median duration of response (months) was longest in LEN+EVE, 13.1; LEN, 7.5; EVE, 8.5. OS analysis showed a trend favoring LEN+EVE vs EVE (HR 0.55; 95% CI 0.30–1.01; P = 0.062); this reached significance (HR 0.51; 95% CI 0.30–0.88; P = 0.024) in an updated analysis on Dec 10, 2014. For LEN+EVE, most common any-grade treatment-emergent adverse events (TEAEs) were diarrhea (84%), decreased appetite (51%), and fatigue (47%). Most common grade ≥ 3 TEAEs were diarrhea (20%), hypertension (14%), and fatigue (10%). Conclusions: LEN+EVE improved PFS and ORR versus EVE alone in this phase II trial of pts with mRCC following prior VEGF-targeted therapy. Updated OS also showed improvement with LEN+EVE. A phase III randomized trial of the combination in mRCC is planned. Clinical trial information: NCT01136733

Primary analysisLEN+EVE
n = 51
n = 52
n = 50
Median survival,
months (95% CI)
PFS14.6 (5.9–20.1)7.4 (5.6–10.2)5.5 (3.5–7.1)
OS25.5 (20.8–25.5)18.4 (13.3–NE)17.5 (11.8–NE)
ORR, n (%)22 (43)14 (27)3 (6)
Median duration
of response,
months (95% CI)
13.1 (3.8–NE)7.5 (3.8–NE)8.5 (7.5–9.4)
Median # of
cycles, (range)
9.0 (1–25)8.5 (1–25)5.0 (1–22)

NE, not evaluable