RESUMO
INTRODUCTION: To examine the magnitude of the clinical benefit from first-line tyrosine kinase inhibitors (TKIs) advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR)-mutations. Areas covered: The present evaluation was restricted to pivotal phase III RCTs in first-line for advanced NSCLC with activating EGFR-mutations. We have subsequently applied the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above pivotal phase III RCTs, to derive a relative ranking of the magnitude of clinically meaningful benefit. Our study evaluated 8 phase III RCTs (including 1710 patients). The ESMO-MCBS reached high grade (grade 4) for all TKIs treatments with at least one phase III RCT for each TKI. Expert commentary: Combining pharmacological costs of drugs with the measure of efficacy, afatinib has the lowest difference in costs per month-PFS gained and a comparable high grade of magnitude of clinical benefit.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Afatinib , Antineoplásicos/economia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/genética , Ensaios Clínicos Fase III como Assunto , Custos de Medicamentos , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/economia , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
We evaluated HER-2/neu status in 100 consecutive ductal breast carcinomas by using the Food and Drug Administration (FDA) and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) scoring systems. With the FDA system, scores were 3+ in 23.0%, 2+ in 25.0%, and 0 or 1+ in 52.0% of cases. With the ASCO/CAP system, scores were 3+ in 16.0%, 2+ in 34.0%, and 0 or 1+ in 50.0%. With the FDA and ASCO/CAP systems, respectively, 3+ cases (n = 23 and 16, respectively) showed high-grade, granular HER-2/neu amplification in 15 (65%) and 14 (88%); low-grade, borderline amplification in 7 (30%) and 1 (6%); and chromosome 17 polysomy without amplification in 1 (4%) and 1 (6%). Concordance between schemes was higher for cases with high-grade, granular HER-2/neu amplification (concordance coefficient, 0.74). Cases with low-grade, borderline HER-2/neu amplification showed poor concordance (concordance coefficient, 0.20). The FDA and ASCO/CAP schemes for HER-2/neu evaluation select patients differently for trastuzumab therapy. Major discordance is present for low-grade, borderline HER-2/neu amplification. FDA low-grade, borderline tumors would be reclassified as without HER-2/neu amplification or as polysomic. The ASCO/CAP scheme has a great concordance coefficient between strong 3+ immunohistochemical cases and cases with high-grade, granular HER-2/neu amplification.