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Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN).

ABSTRACT: BACKGROUND:This was a post hoc analysis of patients with non-squamous histology from a phase III maintenance pemetrexed study in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:The six symptom items' [average symptom burden index (ASBI)] mean at baseline was calculated using the lung cancer symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI ? 25) and performance status (PS: 0, 1) subgroups were analyzed for treatment effect on progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazard models adjusted for demographic/clinical factors. RESULTS:Significantly longer PFS and OS for pemetrexed versus placebo occurred in LSB patients [PFS: median 5.1 versus 2.4 months, hazard ratio (HR) 0.49, P < 0.0001; OS: median 17.5 versus 11.0 months, HR 0.63, P = 0.0012] and PS 0 patients (PFS: median 5.5 versus 1.7 months, HR 0.36, P < 0.0001; OS: median 17.7 versus 10.3 months, HR 0.54, P = 0.0019). Significantly longer PFS, but not OS, occurred in HSB patients (median 3.7 versus 2.8 months, HR 0.50, P = 0.0033) and PS 1 patients (median 4.4 versus 2.8 months, HR 0.60, P = 0.0002). CONCLUSIONS:ASBI and PS are associated with survival for non-squamous NSCLC patients, suggesting that maintenance pemetrexed is useful for LSB or PS 0 patients following induction.

SUBMITTER: Obasaju C

PROVIDER: S-EPMC3660084 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN).

Obasaju C C Bowman L L Wang P P Shen W W Winfree K B KB Smyth E N EN Boye M E ME John W W Brodowicz T T Belani C P CP

Annals of oncology : official journal of the European Society for Medical Oncology 20130404 6

<h4>Background</h4>This was a post hoc analysis of patients with non-squamous histology from a phase III maintenance pemetrexed study in advanced non-small cell lung cancer (NSCLC).<h4>Patients and methods</h4>The six symptom items' [average symptom burden index (ASBI)] mean at baseline was calculated using the lung cancer symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI ≥ 25) and performance status (PS: 0, 1) subgroups were analyzed for treatment effect on progressio ...[more]

PMID: 23559150

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Project description:PurposeTo investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo.Patients and methodsPatients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data.ResultsThe visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib.ConclusionThe significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.

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:BackgroundGemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC).MethodsWe performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software.ResultsEleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW".ConclusionsGemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.

Dataset Information

Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN).

Publications

Identifying the target NSCLC patient for maintenance therapy: an analysis from a placebo-controlled, phase III trial of maintenance pemetrexed (H3E-MC-JMEN).

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