Dataset Information

Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients.

ABSTRACT:

Background

Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data.

Methods

This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed.

Results

A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24-0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37-1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse.

Conclusion

This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.

SUBMITTER: Chen RL

PROVIDER: S-EPMC8071858 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe great efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been identified in patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, it has not yet been established in postoperative adjuvant therapy.Patients and methodsTo compare the prognosis and toxicity of EGFR-TKI-based adjuvant therapy and non-EGFR-TKI-based adjuvant therapy in resected NSCLC with sensitive EGFR mutations, we performed this meta-analysis of all eligible randomized controlled trials (RCTs).ResultsA comprehensive literature search of electronic databases (from inception to December 31, 2017) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology conferences and World Conference on Lung Cancer held between January 2000 and November 2017 were searched to identify relevant trials. Disease-free survival (DFS), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Five RCTs were selected, and 560 participants were included. This meta-analysis demonstrated that EGFR-TKI-based adjuvant therapy was associated with better DFS compared with non-EGFR-TKI-based therapy (HR =0.52, 95% CI 0.34-0.78, P=0.002). Pooled estimate has showed the trend of superiority of EGFR-TKI-based therapy in the aspect of OS (HR =0.65, 95% CI 0.22-1.91, P=0.43); however, the difference was not significant. The incidence rate of grade 3-4 toxicities of EGFR-TKI-based regimens was significantly higher for rash (OR =10.17, 95% CI 2.37-43.63, P=0.002) but lower for vomiting (OR =0.08, 95% CI 0.01-0.61, P=0.02).ConclusionEGFR-TKI-based therapy was associated with better DFS compared with non-EGFR-TKI-based adjuvant therapy in patients with NSCLC harboring EGFR mutations. A trend was found that EGFR-TKI-based regimen improved the OS, though the difference was not significant. Although more OS data are needed, EGFR-TKI-based treatment has the potential to be an alternative of adjuvant therapy for NSCLC with a sensitive EGFR mutation.

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:PurposeA meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC).MethodsPubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ? 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs).ResultsData were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002).ConclusionAddition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.