EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP)
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Non-small cell lung cancer (NSCLC) has a 5-year survival of 5–16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role.
Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp.
Patients and Methods
Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status.
30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3–34.6) vs. (11.0, 95% CI 8.2–16.7); p = 0.002] and OS [(37.8, 95% CI 30.9–44.7) vs. (27.1, 95% CI 12.8–41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0–44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4–42.5) (p < 0.001) and longer PFS (p = 0.043).
Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.
We are grateful for the generous contribution from the Silberman and Buendía families for altruistically promoting the development of cancer research in Colombia.
Compliance with Ethical Standards
Supported by the Foundation for Clinical and Applied Cancer Research (FICMAC, Bogotá, Colombia) research grant 017-2015.
Conflict of Interest
Andrés F. Cardona declares consulting fees or honorarium, support for travel to meetings for the study, manuscript preparation or other purposes, payment for lectures including service on speakers’ bureaus for Roche, Pfizer, Bristol-Myers Squibb, Merck, MSD, and AstraZeneca. Noemí Reguart declares advisory roles for Boehringer Ingelheim, Roche, AstraZeneca, Bristol Myers, and Pfizer, lectures and speaker bureaus for Boehringer Ingelheim, Roche, AstraZeneca, Bristol Myers, and Pfizer, and expert testimony for Boehringer Ingelheim, Roche, AstraZeneca, Bristol-Myers, and Pfizer. Luis Corrales declares that he has participated in advisory boards organized by AstraZeneca and received honoraria from AstraZeneca for lectures in scientific meetings. Oscar Arrieta declares advisory role, lectures, and speaker bureaus and expert testimony for Boehringer Ingelheim, Roche, AstraZeneca, and Lilly. Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Beatriz Wills, Hernán Carranza, Carlos Vargas, Jorge Otero, Claudio Martín, Pilar Archila, July Rodriguez, Jenny Avila, Melissa Bravo, Luis Eduardo Pino, and Rafael Rosell declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.
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