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 Mucciarini & 9 others Virginio Filipazzi, Jessica Menis, Elisa Rizzo, Fausto Barbieri, Erika Rijavec, Fabiana Cecere, Gianluca Spitaleri, Emilio Bria, Silvia Novello

Research output: Contribution to journalArticle

Abstract

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
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Mutation
Disease-Free Survival
Survival
Exons
Sequence Deletion
Codon
Leucine
Population
Multicenter Studies
Observational Studies
Arginine
Adenocarcinoma

Cite this

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

In: Clinical Lung Cancer, Vol. 19, No. 1, 01.2018, p. 93-104.

Research output: Contribution to journalArticle

Pilotto, S, Rossi, A, Vavalà, T, Follador, A, Tiseo, M, Galetta, D, Morabito, A, Di Maio, M, Martelli, O, Caffo, O, Piovano, PL, Cortinovis, D, Zilembo, N, Casartelli, C, Banna, GL, Ardizzoia, A, Barzelloni, ML, Bearz, A, Genestreti, G, Mucciarini, C, Filipazzi, V, Menis, J, Rizzo, E, Barbieri, F, Rijavec, E, Cecere, F, Spitaleri, G, Bria, E & Novello, S 2018, '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', Clinical Lung Cancer, vol. 19, no. 1, pp. 93-104. https://doi.org/10.1016/j.cllc.2017.05.016
Pilotto, Sara ; Rossi, Antonio ; Vavalà, Tiziana ; Follador, Alessandro ; Tiseo, Marcello ; Galetta, Domenico ; Morabito, Alessandro ; Di Maio, Massimo ; Martelli, Olga ; Caffo, Orazio ; Piovano, Pier Luigi ; Cortinovis, Diego ; Zilembo, Nicoletta ; Casartelli, Clelia ; Banna, Giuseppe Luigi ; Ardizzoia, Antonio ; Barzelloni, Maria Luisa ; Bearz, Alessandra ; Genestreti, Giovenzio ; Mucciarini, Claudia ; Filipazzi, Virginio ; Menis, Jessica ; Rizzo, Elisa ; Barbieri, Fausto ; Rijavec, Erika ; Cecere, Fabiana ; Spitaleri, Gianluca ; Bria, Emilio ; Novello, Silvia. / 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. In: Clinical Lung Cancer. 2018 ; Vol. 19, No. 1. pp. 93-104.
@article{80d6a135ebd8499d937886b9d980aff4,
title = "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",
abstract = "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.",
author = "Sara Pilotto and Antonio Rossi and Tiziana Vaval{\`a} and Alessandro Follador and Marcello Tiseo and Domenico Galetta and Alessandro Morabito and {Di Maio}, Massimo and Olga Martelli and Orazio Caffo and Piovano, {Pier Luigi} and Diego Cortinovis and Nicoletta Zilembo and Clelia Casartelli and Banna, {Giuseppe Luigi} and Antonio Ardizzoia and Barzelloni, {Maria Luisa} and Alessandra Bearz and Giovenzio Genestreti and Claudia Mucciarini and Virginio Filipazzi and Jessica Menis and Elisa Rizzo and Fausto Barbieri and Erika Rijavec and Fabiana Cecere and Gianluca Spitaleri and Emilio Bria and Silvia Novello",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2018",
month = "1",
doi = "10.1016/j.cllc.2017.05.016",
language = "English",
volume = "19",
pages = "93--104",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Outcomes of First-Generation EGFR-TKIs Against Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations

T2 - A Post Hoc Analysis of the BE-POSITIVE Study

AU - Pilotto, Sara

AU - Rossi, Antonio

AU - Vavalà, Tiziana

AU - Follador, Alessandro

AU - Tiseo, Marcello

AU - Galetta, Domenico

AU - Morabito, Alessandro

AU - Di Maio, Massimo

AU - Martelli, Olga

AU - Caffo, Orazio

AU - Piovano, Pier Luigi

AU - Cortinovis, Diego

AU - Zilembo, Nicoletta

AU - Casartelli, Clelia

AU - Banna, Giuseppe Luigi

AU - Ardizzoia, Antonio

AU - Barzelloni, Maria Luisa

AU - Bearz, Alessandra

AU - Genestreti, Giovenzio

AU - Mucciarini, Claudia

AU - Filipazzi, Virginio

AU - Menis, Jessica

AU - Rizzo, Elisa

AU - Barbieri, Fausto

AU - Rijavec, Erika

AU - Cecere, Fabiana

AU - Spitaleri, Gianluca

AU - Bria, Emilio

AU - Novello, Silvia

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.cllc.2017.05.016

DO - 10.1016/j.cllc.2017.05.016

M3 - Article

VL - 19

SP - 93

EP - 104

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

IS - 1

ER -