Randomized, open-label phase II study of motesanib or bevacizumab in combination with paclitaxel and carboplatin (P/C) for advanced nonsquamous non-small cell lung cancer (NSCLC).
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.7528
ISSN1527-7755
AutoresG. R. Blumenschein, Fairooz F. Kabbinavar, Hari Menon, Tony Mok, J. Stephenson, J.T. Beck, K C Lakshmaiah, Karolyn Kracht, R Sikorski, Lee S. Schwartzberg,
Tópico(s)Hepatocellular Carcinoma Treatment and Prognosis
Resumo7528 Background: Motesanib is a small molecule antagonist of VEGF (1, 2, and 3), PDGF, and Kit receptors. The objective of this study was to estimate the objective response rates (ORR) of motesanib (two dosing cohorts) + P/C and bevacizumab + P/C in patients (pts) with NSCLC. Methods: Adults with confirmed unresectable, stage IIIB with pericardial or pleural effusion or stage IV/recurrent nonsquamous NSCLC and ECOG 0 or 1 were randomized (1:1:1) to receive paclitaxel (200 mg/m2) + carboplatin (AUC 6 mg/mL/min) on day 1 of each 3-week cycle (6 cycles max) plus motesanib orally from day 1 of cycle 1 at either (Arm A) 125 mg once daily (QD) continuously or (Arm B) 75 mg twice daily (BID) for 5 days followed by 2 treatment-free days; or (Arm C) P/C + bevacizumab 15 mg/kg once every 3 weeks on day 1 of each cycle until disease progression or intolerability. The primary endpoint was ORR per RECIST by independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (AEs). Results: 181 pts received at least 1 dose of treatment (Arms A/B/C, n = 59/62/60). In pts with measurable disease at baseline (Arms A/B/C, n = 57/60/62) ORR in Arms A/B/C was 30/23/37%, with no complete responses. At time of data cut-off, median PFS in months (95% CI) was 8.4 (6.1, 10.1) in Arm A, 6.2 (4.7, 6.3) in Arm B, and 9.0 (7.4, 11.0) in Arm C. OS in months was 15.2 (8.5, 20.2) in Arm A, 13.9 (8.6, 18.5) in Arm B, 15.2 (10.2, 18.2) in Arm C. AEs of interest (all grades) included cholecystitis (5/8/0%), hemorrhagic events (22/24/18%), deep vein thrombosis (3/0/2%), and pulmonary embolism (3/2/3%). In Arms A/B/C, grade 3 AEs occurred in 46/58/50%, grade 4 AEs in 10/3/5%, and grade 5 AEs (excluding NSCLC progression) in 7/16/7% of pts. The most common grade ≥ 3 AEs were diarrhea (Arms A/B/C, 19/11/3%), dehydration (17/11/3%), pneumonia (7/10/2%) and neutropenia (7/8/13%). Conclusions: The estimated efficacy of motesanib 125 mg QD + P/C was similar to bevacizumab + P/C. Motesanib BID dosing had relatively lower efficacy than the other arms. The data support further study of motesanib 125 mg QD + P/C in nonsquamous NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, AstraZeneca, Eisai, Lilly, Pfizer, Roche Amgen Amgen, AstraZeneca, Lilly, Pfizer, Roche Amgen
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