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Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with Carboplatin and Paclitaxel plus bevacizumab.

ABSTRACT: Severe (grade >or= 3) pulmonary hemorrhage (PH) in advanced non-small-cell lung cancer was observed in two prospective, randomized, phase II (N = 99) and phase III (N = 878) trials of bevacizumab plus carboplatin and paclitaxel. Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH.Six patients with PH from the phase II trial, 15 potential PH patients with hemorrhage at any site from the phase III trial, and their matched controls were evaluated with review of baseline and on-treatment radiographs by an independent radiology facility, blinded to patient/control status. Patients with severe (grade >or= 3) PH from each trial were matched with up to three controls based on sex, age group, histology (phase II), or sex and age group (phase III).Seven PH patients in the phase III trial were identified as severe PH. Six of the patients were early onset (occurred < 150 days of initiating bevacizumab) and one was late onset. Baseline tumor cavitation, not tumor location, was identified as the only potential risk factor for patients with early onset. Combined analysis of severe PH patients from the phase II and phase III trials (n = 13), compared with their pooled matched controls (n = 42), did not identify any additional baseline radiographic or clinical variables associated with PH.PH was an uncommon event. Based on these analyses, baseline tumor cavitation may be a potential risk factor for PH. No other baseline clinical variables were predictive for PH although the number of events was small.

SUBMITTER: Sandler AB

PROVIDER: S-EPMC3527732 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with Carboplatin and Paclitaxel plus bevacizumab.

Sandler Alan B AB Schiller Joan H JH Gray Robert R Dimery Isaiah I Brahmer Julie J Samant Meghna M Wang Lisa I LI Johnson David H DH

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20090217 9

<h4>Purpose</h4>Severe (grade >or= 3) pulmonary hemorrhage (PH) in advanced non-small-cell lung cancer was observed in two prospective, randomized, phase II (N = 99) and phase III (N = 878) trials of bevacizumab plus carboplatin and paclitaxel. Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH.<h4>Patients and methods</h4>Six patients with PH from the phase II trial, 15 potential PH patients with hemorrhage at any s ...[more]

PMID: 19224857

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Project description:BackgroundPF-06439535 is a bevacizumab biosimilar. We aimed to compare the efficacy and safety of PF-06439535 with that of reference bevacizumab (Avastin®) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC).MethodsIn this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries. Participants were randomized 1:1 to receive PF-06439535 plus paclitaxel and carboplatin or bevacizumab-EU plus paclitaxel and carboplatin on day 1 of each 21-day cycle for 4-6 cycles, followed by blinded monotherapy with PF-06439535 or bevacizumab-EU until disease progression, unacceptable toxicity, withdrawal of consent, or the end of the study. Randomization was stratified by region, sex, and smoking history. The primary endpoint was objective response rate (ORR) in accordance with RECIST 1.1, based on responses achieved by week 19 and confirmed by week 25.ResultsBetween 21 May 2015 and 14 November 2016, 719 patients were randomized to the PF-06439535 group (n = 358) or the bevacizumab-EU group (n = 361). As of data cutoff for analysis of the primary endpoint (8 May 2017), 45.3% (95% confidence interval [CI] 40.01-50.57) of patients in the PF-06439535 group and 44.6% (95% CI 39.40-49.89) of patients in the bevacizumab-EU group achieved an objective response by week 19 that was confirmed by week 25. The unstratified ORR risk ratio was 1.015 (95% CI 0.863-1.193; 90% CI 0.886-1.163), and the unstratified ORR risk difference was 0.653% (95% CI - 6.608 to 7.908); all three CIs fell within pre-specified equivalence margins. Using final data after study completion (22 December 2017), no notable differences in progression-free survival or overall survival were observed between the groups. The most frequently reported grade 3 or higher treatment-emergent adverse events were hypertension, neutropenia, and anemia. There were no clinically meaningful differences in safety, pharmacokinetics, or immunogenicity across treatment groups.ConclusionAmong patients with advanced non-squamous NSCLC, PF-06439535 demonstrated similarity to bevacizumab-EU in terms of efficacy. Safety profiles for the two treatments were comparable.Trial registrationClinicalTrials.gov, NCT02364999.FundingPfizer.

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

Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with Carboplatin and Paclitaxel plus bevacizumab.

Publications

Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with Carboplatin and Paclitaxel plus bevacizumab.

Similar Datasets

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