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

ABSTRACT: 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.

SUBMITTER: Yan H

PROVIDER: S-EPMC4611484 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Yan Han H Li Qin Q Wang Wei W Zhen Hongchao H Cao Bangwei B

Scientific reports 20151020

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 ...[more]

PMID: 26481697

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Project description:The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P?=?0.02). In selected patients by EGFR-mutation, both mutation positive (HR?=?0.48, 95% CI 0.28-0.83, P?=?0.009) and negative (HR?=?0.84, 95% CI 0.72-0.98, P?=?0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P?=?0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR?=?0.51, 95% CI 0.35-0.74, P?=?0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR?=?2.01, 95% CI 1.11-3.63; P?=?0.02) and diarrhea (RR?=?2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

Project description:BackgroundThe combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.MethodsEMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.ResultsA total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79) and rash (RR = 7.43, 95% CI = 4.56-12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93) and fatigue (RR = 9.60, 95% CI = 2.28-40.86) compared with EGFR TKI monotherapy.ConclusionsThe synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.

Project description:ObjectiveThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.MethodsA systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.ResultsA total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50-0.64; P <0.00001) and 0.70 (95% CI = 0.54-0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10-1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.ConclusionsCompared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.

Project description:BACKGROUND:The treatment strategy for brain metastasis (BM) in patients with epidermal growth factor receptor (EGFR) -mutant lung adenocarcinoma (LAC) remains controversial. In the present study, we compared the efficacy of brain radiotherapy (RT) in combination with tyrosine kinase inhibitors (TKIs) and TKIs alone for advanced LAC patients with EGFR mutations and BM. METHODS:We retrospectively studied 78 patients diagnosed with EGFR-mutant LAC who developed BM. These patients were divided into two groups: 49 patients in the combination treatment group who received brain RT in combination with EGFR-TKIs (including 23 patients with asymptomatic BM before RT); 29 patients in the TKI group who received EGFR-TKI targeted therapy alone (including 22 patients with asymptomatic BM before TKI treatment). RESULTS:The median intracranial progression-free survival (iPFS) of the combination treatment group was longer than that of the TKI alone group (21.5 vs. 15?months; P?=?0.036). However, there were no significant differences in median progression-free survival (PFS, 12 vs. 13?months; P?=?0.242) and median overall survival (mOS, 36 vs. 23?months; P?=?0.363) between the two groups. Further analysis of asymptomatic BM showed that both the median iPFS and the mOS of the combination treatment group were significantly longer than for the TKI alone group (iPFS, 21.5 vs. 14.8?months, P?=?0.026; mOS, 36 vs. 23?months, P?=?0.041). Cox multivariate regression analysis found no independent adverse predictors of iPFS in all patients. CONCLUSIONS:The synchronous combination of brain RT and TKIs was superior to EGFR-TKIs alone for EGFR-mutant LAC patients with BM. The combination treatment group exhibited longer iPFS, while the PFS and OS were not significantly different between the two groups. In addition, the combination treatment could result in better iPFS and OS in those with asymptomatic BM. Therefore, addition of brain RT was useful for intracranial metastatic lesions.

Project description:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Project description:Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been used for the first-line treatment of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, some patients fail to benefit from this treatment. The aim of this study is to analyze whether or not clinical-selected patients (Asian, adenocarcinoma histology, non-smoking) and EGFR mutation-selected patients benefit from EGFR-TKIs or chemotherapy. Our results could be used as basis to guide clinical therapy.Randomized controlled trials evaluating the efficacy of EGFR-TKIs versus chemotherapy as first-line treatments of NSCLC were obtained from electronic databases, namely, PubMed, Embase, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology, and China Biology Medicine disc. Assessment, data collection, and statistical analysis were performed according to Cochrane Handbook 5.1.0.A total of 14 randomized controlled trials with 5,000 patients were included in this study. Compared with the chemotherapy group, EGFR-TKI therapy group in EGFR mutation-selected NSCLC patients showed a higher response rate (RR=2.31; 95%CI: 1.88-2.84) and more significant improvement in progression free survival (PFS; HR=0.39; 95%CI: 0.30-0.49); by contrast, no significant difference was observed in overall survival (OS; HR=0.99; 95%CI: 0.84-1.16). The response rate of clinical-selected patients treated with EGFR-TKI significantly increased (RR=1.30; 95%CI: 1.15-1.47) compared with that of the patients treated with chemotherapy; PFS (HR=0.93; 95%CI: 0.58-1.49) and OS (HR=0.91; 95%CI: 0.81-1.02) of the two groups did not significantly differ. Likewise, the PFS and the OS of the unselected patients in the EGFR-TKI treatment group and the chemotherapy group did not significantly differ, although the OS of the former was shorter than that of the latter.EGFR mutation-selected patients received more benefits from EGFR-TKI first-line treatment than other treatments. First-line EGFR-TKI treatment was recommended for clinically selected patients who were unsuitable for themotherapy. By comparison, first-line EGFR-TKI treatment was not a suitable choice for unselected patients.

Dataset Information

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

Publications

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

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