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

Konference: 2015 51th ASCO Annual Meeting - účast ČR

Kategorie: Genitourinární nádory

Téma: Genitourinary (Nonprostate) Cancer

Číslo abstraktu: 4506

Autoři: MD Robert J. Motzer; MD Thomas Hutson; Hilary Glen, PhD, MSc, MRCP, MBCHB; MD Dror Michaelson, Ph.D.; Ass Prof., Dr. Ana M. Molina; prof. Timothy Eisen; prof. dr hab. n. med. Jacek Jassem; MD Jakub Zolnierek; Dr. Pablo Maroto; Begona Mellado; prof. MUDr. Bohuslav Melichar, Ph.D.; MUDr. Jiří Tomášek, Ph.D.; Han-Joo Kim; Karen Wood; MD Corina Dutcus; MD James M. G. Larkin

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 analysis LEN+EVE
n = 51
n = 52
n = 50
Median survival,
months (95% CI)
PFS 14.6 (5.9–20.1) 7.4 (5.6–10.2) 5.5 (3.5–7.1)
OS 25.5 (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)


J Clin Oncol 33, 2015 (suppl; abstr 4506)


Datum přednesení příspěvku: 1. 6. 2015