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The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis.

ABSTRACT: Platinum regimens still play a key role in chemotherapy for incurable non-small cell lung cancer (NSCLC). Although guidelines list many platina regimens, the best regimens have not yet clarified. Electronic searches were carried out during November 26th-28th, 2016. We included individually randomized trials comparing two or more platinum regimes for incurable chemo-naive NSCLC published in English full papers. The platinum doublets should be either Cisplatin (CDDP), Carboplatin (CBDCA), or Nedaplatin (CDGP) plus one of the third-generation agents. The platinum triplet should be the doublet plus bevacizumab (BEV). The data were independently extracted and cross-checked by two investigators. We did not observed heterogeneity (whole network level Q?=?28.9, df?=?34, P?=?0.717) among 59 pairwise comparisons from 45 studies with 16141 cases for the primary outcome, hazard ratio for overall survival (HRos). Using CBDCA?+?Paclitaxel (PTX)?+?BEV as a common comparator, CDGP?+?Docetaxel (DTX) (HRos?=?0.98, 95%CI: 0.75-1.29, P?=?0.884), CDDP?+?Tegafur gimeracil oteracil (S1) (HRos?=?1.23, 95%CI: 0.96-1.57, P?=?0.099), CBDCA?+?S1 (HRos?=?1.23, 95%CI: 0.99-1.53, P?=?0.062), and CDGP?+?Gemcitabine (GEM) (HRos?=?1.24, 95%CI: 0.71-2.17, P?=?0.45) did not have significantly poorer HRos. We suggest that these regimens as acceptable first-choice regimens.

SUBMITTER: Horita N

PROVIDER: S-EPMC5640659 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis.

Horita Nobuyuki N Nagashima Akimichi A Nakashima Kentaro K Shibata Yuji Y Ito Kentaro K Goto Atsushi A Yamanaka Takeharu T Kaneko Takeshi T

Scientific reports 20171013 1

Platinum regimens still play a key role in chemotherapy for incurable non-small cell lung cancer (NSCLC). Although guidelines list many platina regimens, the best regimens have not yet clarified. Electronic searches were carried out during November 26th-28th, 2016. We included individually randomized trials comparing two or more platinum regimes for incurable chemo-naive NSCLC published in English full papers. The platinum doublets should be either Cisplatin (CDDP), Carboplatin (CBDCA), or Nedap ...[more]

PMID: 29030633

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Project description:BackgroundOur goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).MethodsThe protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.ResultsA total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.ConclusionPatients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.

Project description:PurposePalliative radiation therapy (RT) can improve quality of life but also incurs time and financial costs. The aim of this study was to evaluate factors associated with use and intensity of palliative RT for incurable non-small cell lung cancer (NSCLC).Methods and materialsThis was a retrospective analysis of Medicare's Surveillance, Epidemiology and End Results data. We identified patients who were diagnosed with incurable (American Joint Committee on Cancer 6th edition stage IIIB with malignant effusion or stage IV) NSCLC between 2004 and 2011. Univariable and multivariable logistic regressions were used to identify factors associated with the receipt of palliative RT and the use of >10 fractions during the first course of radiation. Among patients who were treated with radiation, freestanding versus hospital-based center information was collected on the basis of the location of the RT delivery claim.ResultsAmong 55,258 patients with incurable NSCLC, 38% (21,053 patients) received palliative RT during the first year after diagnosis. Among patients who received RT, 56% (11,717 patients) received >10 fractions. On multivariable analysis, factors associated with greater RT use included younger age group (overall P < .01), lower modified Charlson comorbidity score (overall P < .01), female sex (odds ratio [OR]: 1.1; P < .01), marital status (OR: 1.1; P < .01), and chemotherapy use (OR: 3.6; P < .01). Predictors for >10 fractions were chemotherapy use (OR: 1.7; P < .01) and treatment at a freestanding versus hospital-based facility (58% vs 43%; OR: 1.7; P < .01).ConclusionsMore than a third of patients diagnosed with incurable lung cancer receive palliative RT and 56% received >10 fractions. The use of RT varied by region and patient characteristics, and patients treated at freestanding RT centers were more likely to receive >10 fractions. Further research into factors that influence treatment decisions including potential financial incentives may contribute to the high value and strategic utilization of palliative RT.

Project description:ImportanceRandomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.ObjectiveTo assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.Data sourcesFull-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.Study selectionPhase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.Data extraction and synthesisData extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.Main outcomes and measuresTwo-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.ResultsEight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).Conclusions and relevanceIn this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

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The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis.

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The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis.

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