Cancer Chemotherapy Reviews
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REVIEW ARTICLE

Outcome of Patients with Lung Adenocarcinoma Harboring Common and Rare Epidermal Growth Factor Receptor Mutations in Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

April-June 2015, Volume 02, Number 2
Eduardo Amieva-Rivera, Jorge Negueb Martínez-Hernández, Mariana López-Mejía, Jaime de la Garza-Salazar and Óscar Arrieta-Rodríguez
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
 

Background: Approximately 10-40% of patients with adenocarcinoma have somatic mutations in the epidermal growth factor receptor. The presence of the common activating epidermal growth factor receptor mutations (DEL 19/L858R) is closely associated with sensitivity to reversible tyrosine kinase inhibitors. Conversely, rare mutations (G719X/L861Q/768I/T790M/Exon 20 insertion) have usually been associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors and poorer prognosis. Methods: We conducted a literature review up to January 2015 using PubMed and Embase to identify phase II and III randomized trials and case series that assessed first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy versus standard platinum-based chemotherapy regimens in previously untreated patients with positive epidermal growth factor receptor mutation advanced lung adenocarcinoma with uncommon epidermal growth factor receptor mutations and response to epidermal growth factor receptor tyrosine kinase inhibitors, and compared them with our previous study to determine differences in response rates as well as clinical factors among patients with common and rare mutations. Review: Overall, in patients with epidermal growth factor receptor mutations, women have shown a better progression-free survival to epidermal growth factor receptor tyrosine kinase inhibitors compared to men, and also, rare epidermal growth factor receptor mutations are more frequent in high-grade adenocarcinomas than in low-grade tumors. We report a significant number of patients with epidermal growth factor receptor mutations; most of the studies refer to the status of the mutation, but only a few of them report the type of mutation. Concerning common mutations, these studies report a longer progression-free survival with epidermal growth factor receptor tyrosine kinase inhibitors versus chemotherapy (9.2-13.6 vs. 4.6-6.9 months; p < 0.001). However, progression-free survival for uncommon mutations with epidermal growth factor receptor tyrosine kinase inhibitors versus standard chemotherapy was lower (1.4-3.9 vs. 5.1-5.9 months, respectively), with no significant difference. Conclusion: Our findings suggest that due to their low response rates and short progression-free survival in response to epidermal growth factor receptor tyrosine kinase inhibitors, only patients with uncommon epidermal growth factor receptor mutations should receive platinum-based chemotherapy as first-line treatment. Consequently, epidermal growth factor receptor tyrosine kinase inhibitors could be reserved as a second- or third-line treatment.

 
 
Key words:
EGFR mutation. EGFR tyrosine kinase inhibitor. Adenocarcinoma lung cancer. Deletion exon 19. L858R mutation. Uncommon mutations.
 
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