Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

Salvia, Anna La; Rossi, Antonio; Galetta, Domenico; Gobbini, Elisa; Luca, Emmanuele De; Novello, Silvia; Maïo, Massimo Di

doi:10.1016/j.cllc.2016.08.006

Cited by 11 publications

(8 citation statements)

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“…Erlotinib, a first generation EGFR-TKI, is economical and efficacious for advanced NSCLC patients. Pivotal trials of erlotinib demonstrated meaningful improvements in both progression-free survival (PFS) and overall response rate (ORR) compared with the standard platinum-doublet chemotherapy in EGFR mutant NSCLC patients (Hirsch et al, 2011 ; La Salvia et al, 2017 ; Yoshida et al, 2017 ). The BR21 study confirmed that erlotinib increased overall survival (OS) in patients who were unsuitable for other treatments, with strong efficacies in East Asians, non-smokers and patients with lung adenocarcinomas (Florescu et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

Chen

Liu

et al. 2018

Front. Pharmacol.

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The efficacy of erlotinib treatment for advanced non-small cell lung cancer (NSCLC) is due to its action as an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Patients treated with erlotinib experience different drug responses. The effect of germline mutations on therapeutic responses and adverse drug responses (ADRs) to erlotinib in Chinese patients requires elucidation. Sixty Han Chinese advanced non-small cell lung cancer patients received erlotinib monotherapy and, for each participant, 76 candidate genes (related to EGFR signaling, drug metabolism and drug transport pathways) were sequenced and analyzed. The single-nucleotide polymorphisms (SNPs) rs1042640 in UGT1A10, rs1060463, and rs1064796 in CYP4F11, and rs2074900 in CYP4F2 were significantly associated with therapeutic responses to erlotinib. Rs1064796 in CYP4F11 and rs10045685 in UGT3A1 were significantly associated with adverse drug reaction. Moreover, analysis of a validation cohort confirmed the significant association between rs10045685 in UGT3A1 and erlotinib adverse drug response(unadjusted p = 0.015). This study provides comprehensive, systematic analyses of genetic variants associated with responses to erlotinib in Chinese advanced non-small cell lung cancer patients. Newly-identified SNPs may serve as promising markers to predict responses and safety in erlotinib-treated advanced non-small cell lung cancer patients after chemotherapy doublet.

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Section: Introductionmentioning

confidence: 99%

Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

Chen

Liu

et al. 2018

Front. Pharmacol.

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“…Using a strategy for an intercalating and maintenance use of gefitinib with chemotherapy, we demonstrated that, compared to chemotherapy alone, gefitinib significantly prolonged OS. In a previous meta-analysis of RCTs (6 with erlotinib, 4 with gefitinib), intercalated combination was associated with a significant improvement in overall survival (OS; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71–0.95; P = 0.01) 29 . The results from the current study supported the notion that intercalating gefitinib in select patients (high probability of EGFR mutation but no testing results) is a viable option.…”

Section: Discussionmentioning

confidence: 99%

Intercalating and maintenance gefitinib plus chemotherapy versus chemotherapy alone in selected advanced non-small cell lung cancer with unknown EGFR status

Hong

et al. 2017

Sci Rep

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Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15–25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31–0.56; P < 0.001). Overall survival (OS) was also longer in the gefitinib arm (20.1 vs. 15.4 months; HR: 0.68; 95% CI 0.48–0.97; P = 0.0323). Adverse events, including diarrhea, dermal reaction and thrombocytopenia, were more common in the gefitinib arm. In conclusion, intercalating and maintenance gefitinib treatment is a viable option for advanced NSCLC patients with unknown EGFR mutation status in subpopulations with high EFGR mutation rate.

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“…On the basis of published randomized trials, a recent meta-analysis concluded that intercalated treatment is superior to the comparator arm. 24 While this meta-analysis offered a valuable insight into an area which is not in the main stream of current clinical research, the question of efficacy of intercalated treatment is too complex to be answered by a simple comparison.…”

Section: Discussionmentioning

confidence: 99%

“…This aspect was clearly presented in a recent review: apart from the expected skin toxicity and diarrhea, intercalated schedules do not present a disproportional burden to patients. 24 …”

Section: Discussionmentioning

confidence: 99%

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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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Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

Cited by 11 publications

References 47 publications

Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

Intercalating and maintenance gefitinib plus chemotherapy versus chemotherapy alone in selected advanced non-small cell lung cancer with unknown EGFR status

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

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