A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Yu, Hui; Zhang, Jian; Wu, Xianghua; Luo, Zhiguo; Wang, Huijie; Sun, Si; Peng, Wei; Qiao, Jie; Feng, Yu; Wang, Jialei; Chang, Jianhua

doi:10.4161/cbt.28874

Cited by 25 publications

(15 citation statements)

References 31 publications

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“…By reading the title, abstract, and full text of each article, unrelated trials that did not meet the inclusion criteria were excluded. Ten RCTs 3 4 15 16 17 18 19 20 21 22 with a total of 1,660 patients compared the intercalated combination of chemotherapy and EGFR TKIs to chemotherapy alone or EGFR TKIs alone and were found eligible for this systematic review ( Table 1 ). In accordance with the Cochrane Handbook for Systematic Reviews of Interventions, the methodological qualities of each study were independently assessed by two authors and are presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Yan

Wang

et al. 2015

Sci Rep

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Both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied for the treatment of non-small cell lung cancer (NSCLC), but the efficacy of these two treatments in combination is not yet clear. Thus, we sought to evaluate the efficacy of the intercalated combination of these two treatments in NSCLC. The PubMed database, EMBASE, Cochrane Controlled Trials Register, and Chinese Biomedical Database were systematically searched by two researchers for randomized clinical trials (RCTs) that examined the intercalated combination of chemotherapy and EGFR TKIs in NSCLC. Ten studies involving 1,660 patients were included in this systematic review. The statistical results showed that the intercalated combination of chemotherapy and EGFR TKIs significantly improved overall survival (OS) (hazard ratio (HR) = 0.83, 95% confidence interval (CI): 0.70–0.98), progression-free survival (PFS) (HR = 0.65, 95% CI: 0.51–0.84), and the objective response rate (ORR) (risk ratio (RR) = 1.90, 95% CI: 1.22–2.98) compared to chemotherapy alone. Similarly, compared to EGFR TKIs monotherapy, the intercalated combination of chemotherapy and EGFR TKIs seemed superior to EGFR TKIs alone in terms of PFS, ORR and DCR (PFS: HR = 0.75, 95% CI: 0.62–0.91, ORR: RR = 1.49, 95% CI: 1.12–2.00 and DCR: RR = 1.33, 95% CI: 1.15–1.54) in advanced NSCLC therapy.

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Section: Resultsmentioning

confidence: 99%

Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Yan

Wang

et al. 2015

Sci Rep

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“…However, concomitant administration of EGFR-TKIs standard chemotherapy is controversial. The results of previous randomized trials have not shown improved the overall survival among patients with NSCLC [12–23]. However, another trial on the sequential administration of EGFR-TKIs following chemotherapy revealed a significant improvement in overall survival [24].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

et al. 2016

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The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71–0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14–1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90–1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3–4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.

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“…Six trials on treatment-naive patients with EGFR mutant disease reported excellent response rate of 83.1% (range: 76.9% to 84.2%). 30 , 34 , 39 , 42 , 52 , 54 Five of these trials presented data on median PFS ranging from 13.3 to 23.4 months (median PFS for all 5 trials: 18.6 months). This figure does not include an additional trial from this category which reported 86% PFS at 15 months, with no data on median PFS due to relatively short follow-up.…”

Section: Resultsmentioning

confidence: 99%

“…This figure does not include an additional trial from this category which reported 86% PFS at 15 months, with no data on median PFS due to relatively short follow-up. 34 …”

Section: Resultsmentioning

confidence: 99%

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors

Zwitter

Rossi

Maïo

et al. 2017

Radiology and Oncology

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BackgroundWhen treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.MethodsPublished documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson’s correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.ResultsThe series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with non-squamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.ConclusionsMost suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.

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A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Cited by 25 publications

References 31 publications

Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors

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