Pui San Tan

Meta-Analysis of First-Line Therapies in Advanced Non-Small-Cell Lung Cancer Harboring EGFR-Activating Mutations

Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor–activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I2 statistics and predictive intervals (PIs). Results: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non–small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31–0.63; 95% PI, 0.22–0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15–0.42; 95% PI, 0.11–0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26–0.75; 95% PI, 0.20–0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30–1.08; 95% PI, 0.24–1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53–1.92; 95% PI, 0.41–2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27–1.18; 95% PI, 0.22–1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy. Conclusion: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.

Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an Indirect Comparison.

Introduction This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel. Methods A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear regression models. Results There was no statistically significant difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68–1.07). However, there was some evidence that enzalutamide may outperform abiraterone acetate with respect to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30–0.53), radiographic PFS (HR 0.61, 95% CI 0.50–0.74), and PSA response rates (RRs) (OR 10.69, 95% CI 3.92–29.20). Conclusion While there was no statistically significant difference in OS, enzalutamide may be advantageous for secondary endpoints. Findings of this indirect comparison serve to be hypothesis-generating for future head-to-head trials.

Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non-small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: Results by performance status, EGFR mutation, histology and response to previous induction

BACKGROUND Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction. METHODS PubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analysed in a Bayesian hierarchical model. The primary outcome, overall survival (OS), was evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratio (95% credible interval). Secondary outcomes were progression-free survival (PFS) and adverse events. FINDINGS Twelve trials evaluating eight maintenance treatments in 3850 patients were meta-analysed. Selected maintenance treatments showed clinically meaningful benefits of ⩾20% reduction in hazards of death with ⩾90% probability of outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed (nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors (TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1 patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv) switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients, (v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or continue gemcitabine for responders to induction, or (vii) switch to or continue pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease post-induction. INTERPRETATION Maintenance treatments show clinically meaningful survival benefits in good performance status patients with advanced NSCLC not progressing after first-line chemotherapy. Benefits are optimised by targeting specific maintenance to individual patients guided by PS, EGFR mutation status, histology and response to induction.

Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR-Mutated Advanced Non–Small Cell Lung Cancer

Importance The survival of patients with advanced non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. Objective The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. Design, Setting, and Participants For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives. Main Outcomes and Measures The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first- or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC. Results In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first- and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were

Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer - A systematic review and network meta-analysis of 3024 participants.

226 527 vs erlotinib,

Addition of abiraterone, docetaxel, bisphosphonate, celecoxib or combinations to androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC): a network meta-analysis.

231 123 vs gefitinib, and

Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations

219 874 vs afatinib. In Brazil, the ICERs were

A meta-analysis of anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer

162 329,

Ten-year survival in women with primary stage IV breast cancer

180 804, and

Anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer: A meta-analysis.

175 432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from