Outcomes of First-Generation EGFR-TKIs Against Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Post Hoc Analysis of the BE-POSITIVE Study

Sara Pilotto, Antonio Rossi, Tiziana Vavalà, Alessandro Follador, Marcello Tiseo, Domenico Galetta, Alessandro Morabito, Massimo Di Maio, Olga Martelli, Orazio Caffo, Pier Luigi Piovano, Diego Cortinovis, Nicoletta Zilembo, Clelia Casartelli, Giuseppe Luigi Banna, Antonio Ardizzoia, Maria Luisa Barzelloni, Alessandra Bearz, Giovenzio Genestreti, Claudia MucciariniVirginio Filipazzi, Jessica Menis, Elisa Rizzo, Fausto Barbieri, Erika Rijavec, Fabiana Cecere, Gianluca Spitaleri, Emilio Bria, Silvia Novello

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study.

PATIENTS AND METHODS: Data of advanced NSCLC patients with uncommon EGFR mutations who received first-line first-generation EGFR-TKIs in 24 Italian Hospitals were collected. In this analysis we aimed to evaluate overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of EGFR-TKIs in NSCLC patients harboring uncommon EGFR mutations.

RESULTS: Thirty-five patients harboring uncommon EGFR mutations (any mutation other than deletion 19 or substitution of leucine by arginine at codon 858) were included of the original 312 EGFR-mutated cases. Most of them were female (n = 20, 57.1%), former smokers (n = 23, 65.7%), with adenocarcinoma (n = 31, 88.6%). The most frequent EGFR mutations were G719X (n = 6, 17.2%) and L861Q (n = 5, 14.2%). The population presented an ORR of 25.7%, a median PFS of 5.19 months, and a median OS of 14.49 months. When stratified according to type of EGFR mutation, median OS ranged from 3.65 months for unspecified mutations to 21.29 for double EGFR mutations. Median PFS ranged from 1.77 months for unspecified mutations to 20.83 months for concomitant EGFR-anaplastic lymphoma kinase alteration. ORR varied from 0% in exon 18, 20 and double gene alteration to 66.6% in exon 19.

CONCLUSION: Our study supports the existence of a strong outcome heterogeneity within patients harboring uncommon EGFR mutations, which needs to be clarified to achieve a real personalized treatment strategy.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalClinical Lung Cancer
Issue number1
Publication statusPublished - Jan 2018


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