Subgroup analyses and updated overall survival from the phase II trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in metastatic renal cell carcinoma (mRCC).
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.4553
ISSN1527-7755
AutoresThomas E. Hutson, Corina E. Dutcus, Min Ren, Mahadi Baig, Mayer Fishman,
Tópico(s)Cancer Genomics and Diagnostics
Resumo4553 Background: In the randomized phase 2 study of LEN, EVE, and LEN+EVE in mRCC, LEN+EVE significantly improved the primary endpoint median progression-free survival (PFS) vs EVE (14.6 vs 5.5 months [mos]; hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.24–0.68; P= 0.0005). LEN alone (7.4 mos) also improved median PFS vs EVE (HR 0.61; 95% CI 0.38–0.98; P= 0.048). We report PFS outcomes by patient subgroups. Methods: Patients with progressive clear cell mRCC following 1 VEGF-targeted therapy received LEN (24 mg/d), EVE (10 mg/d), or LEN+EVE (18+5 mg/d). Exploratory subgroups included baseline tumor size (sum of tumor diameters), Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, and metastasis site. The data cutoff for the primary analysis was June 13, 2014; updated cutoff (for overall survival [OS] only) was July 31, 2015. Results: Median PFS was improved in LEN+EVE vs EVE in all examined subgroups (Table). In an updated analysis of OS, the median was 25.5 mos (95% CI 16.4–32.1), 19.1 mos (95% CI 13.6–26.2), and 15.4 mos (95% CI 11.8–20.6) for LEN+EVE, LEN, and EVE, respectively. In comparison with EVE, overall survival was longer for LEN+EVE, a trend that was maintained through the cutoff for the updated OS analysis (HR 0.59; 95% CI 0.36–0.96; P= 0.065). Notably, the HR remains < 0.6, and the upper limit of the CI no longer crosses 1. Conclusions: The PFS advantage with LEN+EVE vs EVE was maintained in all examined subgroups. The updated OS analysis demonstrated a trend towards survival benefit with LEN+EVE vs EVE in patients with mRCC following 1 VEGF-targeted therapy. Clinical trial information: NCT 01136733. Median PFS, mos HR (95% CI); P-value (LEN+EVE vs EVE) n LEN n = 52 n LEN+EVE n = 51 n EVE n = 50 MSKCC risk Favorable 11 18.4 12 20.1 12 9.8 0.25 (0.08–0.76); P = 0.009 Intermediate 18 7.2 19 14.6 19 5.5 0.35 (0.15–0.80); P = 0.0243 Poor 23 5.6 20 5.6 19 3.5 0.44 (0.20–0.98); P = 0.0936 Baseline tumor size < Median 27 7.4 24 14.7 25 5.5 0.34 (0.16–0.71); P = 0.0035 ≥ Median 25 7.2 27 11.2 25 5.3 0.39 (0.19–0.80); P = 0.0134 Metastasis site Bone 23 7.2 16 5.4 17 3.6 0.41 (0.18–0.94) Visceral organs 49 7.4 41 9.5 44 5.5 0.44 (0.26–0.77) Lymph nodes 32 8.0 29 14.7 31 5.5 0.28 (0.14–0.58)
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