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Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536.

ABSTRACT: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m(2)), cetuximab (400 mg/m(2) day 1 then 250 mg/m(2) weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m(2) weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner.The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%.This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.

SUBMITTER: Kim ES

PROVIDER: S-EPMC4072123 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536.

Kim Edward S ES Moon James J Herbst Roy S RS Redman Mary W MW Dakhil Shaker R SR Velasco Mario R MR Hirsch Fred R FR Mack Philip C PC Kelly Karen K Heymach John V JV Gandara David R DR

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20131201 12

<h4>Introduction</h4>Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patie ...[more]

PMID: 24189513

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Project description:IntroductionPRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).MethodsPatients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed.ResultsBaseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms.ConclusionsPem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.

Dataset Information

Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536.

Publications

Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536.

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