Acquired Resistance to First-Line Afatinib and the Challenges of Prearranged Progression Biopsies
| Autor: | Rebecca S. Heist, Alice T. Shaw, Alona Muzikansky, Meghan Campo, Jennifer S. Temel, Jeffrey A. Engelman, David E. Gerber, Justin F. Gainor, Panos Fidias, Lecia V. Sequist |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Adult medicine.medical_specialty Radiation-Sensitizing Agents Lung Neoplasms First line Afatinib Biopsy Pilot Projects Disease-Free Survival 03 medical and health sciences T790M 0302 clinical medicine Acquired resistance Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans Prospective Studies EGFR inhibitors Aged Aged 80 and over business.industry Middle Aged Confidence interval Surgery Clinical trial ErbB Receptors 030104 developmental biology Oncology Egfr mutation Drug Resistance Neoplasm 030220 oncology & carcinogenesis Mutation Disease Progression Quinazolines business medicine.drug |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 11(11) |
| ISSN: | 1556-1380 |
| Popis: | Objectives The mechanisms of acquired resistance to the irreversible EGFR inhibitor afatinib are not well documented. We performed this prospective clinical trial to determine the prevalence of the mutation T790M in afatinib-resistant patients. Methods Eligible patients had EGFR mutations; they were tyrosine kinase inhibitor–naive and were treated with afatinib, 40 mg daily. At enrollment, patients consented to a future repeat biopsy at the time of acquired resistance. Results A total of 24 patients were enrolled. The objective response rate was 58% (95% confidence interval [CI]: 37–78) with a median progression-free survival of 11.4 months (95% CI: 5.9–13.7) and median overall survival of 20.8 months (95% CI: 15.1–40.5). Of the 24 patients enrolled, 23 progressed and only 14 completed repeat biopsy at time of progression, with 11 samples sufficient for molecular analysis. Of those 11 patients, four (36% [95% CI: 10.9–69.2]) harbored T790M. Conclusions T790M is likely a common resistance mechanism in patients treated with first-line afatinib. Although repeat biopsies at progression are crucial in elucidating resistance mechanisms, this study suggests that clinical and technical issues often limit their feasibility, highlighting the importance of developing noninvasive tumor-genotyping strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|