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|Title:||Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma|
|Author:||Finn, Richard S.|
Zhu, Andrew X.
Sung, Max W.
Baron, Ari D.
Dutcus, Corina E.
Siegel, Abby B.
Llovet i Bayer, Josep Maria
|Abstract:||PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti-PD-1 antibody) in unresectable HCC (uHCC). PATIENTS AND METHODS In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight $ 60 kg, 12 mg; , 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21- day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase). RESULTS A total of 104 patients were enrolled. No DLTs were reported (n 5 6) in the DLT phase; 100 patients (expansion phase; included n 5 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n 5 29) or C disease (n 5 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade $ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified. CONCLUSION Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.|
|Note:||Reproducció del document publicat a: https://doi.org/10.1200/JCO.20.00808|
|It is part of:||Clinical Oncology, 2020, vol. 38, num. 26, p. 2960-2970|
|Appears in Collections:||Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)|
Articles publicats en revistes (Medicina)
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