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First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

ABSTRACT: BACKGROUND:The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with wild-type driver genes in a real-world setting. METHODS:We retrospectively collected the medical records of advanced NS-NSCLC patients with wild-type driver genes administered first-line PemPBev or PacCBev therapy at Shanghai Chest Hospital between January 2014 and June 2016, and analyzed the differences in survival outcomes, efficacy, and safety between PemPBev and PacCBev treatment. RESULTS:A total of 390 patients were included in our analysis: 249 in the PemPBev group and 141 in the PacCBev group. Patients administered PemPBev experienced significantly improved progression-free survival (PFS) and overall survival (OS) compared to those administered PacCBev (PFS 7.5 vs. 6.2?months, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.53-0.84, P

SUBMITTER: Chang Q

PROVIDER: S-EPMC6501044 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

Chang Qing Q Zhang Yanwei Y Xu Jianlin J Zhong Runbo R Qiang Huiping H Zhang Bo B Han Baohui B Qian Jialin J Chu Tianqing T

Thoracic cancer 20190322 5

<h4>Background</h4>The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with wild-type driver genes in a real-world setting.<h4>Methods</h4>We retrospectively collected the medical records of advanced NS-NSCLC patients with wild-type driver genes administered first-line PemPBev or Pa ...[more]

PMID: 30900826

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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.

Project description:ObjectiveTo evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).MethodsA cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity.ResultsOne hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response.ConclusionOverall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.

Project description:A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older.To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC.Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare.Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009.The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings.Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.

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:ImportanceChemotherapy is a mainstay treatment of metastatic non-small cell lung cancer. However, little is known about the comparative risk of hospitalization associated with commonly used chemotherapy regimens.ObjectiveTo evaluate the real-world association of specific lung cancer chemotherapy regimens with measures of acute hospital care (primary objective) and survival (secondary objective).Design, setting, and participantsRetrospective, propensity-matched, cohort study using the Surveillance, Epidemiology, and End Results-Medicare linked data for cancer diagnoses between 2008 and 2013, with follow-up through 2014. Patients were Medicare beneficiaries 66 years of age or older receiving initial chemotherapy for treatment of stage IV, nonsquamous, non-small cell lung cancer. Analyses were performed between September 2017 and April 2018.ExposuresReceipt of chemotherapy with carboplatin-pemetrexed or carboplatin-paclitaxel, with or without concurrent bevacizumab.Main outcomes and measuresThe primary outcome was risk of hospitalization within 30 days of chemotherapy initiation. Secondary measures included cumulative 90-day hospitalizations, 90-day mean hospital-free survival time, and overall survival.ResultsOf the 3310 eligible patients, 1823 received carboplatin-pemetrexed, and 1487 received carboplatin-paclitaxel. The median age at diagnosis was 73 years (interquartile range, 69-77 years), 1784 patients (53.9%) were men, and 2909 patients (87.9%) were non-Hispanic white. In total, 2182 patients were included in the propensity-matched analysis. The 30-day hospitalization risk was 20.7% (95% CI, 18.3%-23.1%) among patients receiving carboplatin-pemetrexed vs 26.0% (95% CI, 23.4%-28.6%) among patients receiving carboplatin-paclitaxel (5.3% difference; P?=?.003). The 90-day cumulative hospitalizations did not differ significantly between the 2 treatment groups; however, the 90-day mean hospital-free survival time was improved for patients receiving carboplatin-pemetrexed (68.4 days [95% CI, 66.5-70.4 days] vs 63.6 days [95% CI, 61.6-65.7 days]; P?=?.001). The median survival time was 9.0 months (95% CI, 8.4-9.5 months) with carboplatin-pemetrexed therapy vs 7.6 months (95% CI, 7.0-8.4 months) with carboplatin-paclitaxel therapy (P?=?.005). Stratified analyses showed no association of bevacizumab use with hospitalization risk or survival when combined with either chemotherapy regimen.Conclusions and relevanceThe findings from this study suggest that patients receiving carboplatin-pemetrexed compared with those receiving carboplatin-paclitaxel have a lower 30-day hospitalization risk, a greater 90-day hospital-free survival, and improved overall survival. Information about hospitalization risk may provide valuable context for evaluating real-world cancer treatment outcomes.

Dataset Information

First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

Publications

First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

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