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

S. Pilotto, A. Rossi, T. Vavalà, A. Follador, M. Tiseo, D. Galetta, A. Morabito, M. Di Maio, O. Martelli, O. Caffo, P.L. Piovano, D. Cortinovis, N. Zilembo, C. Casartelli, G.L. Banna, A. Ardizzoia, M.L. Barzelloni, A. Bearz, G. Genestreti, C. MucciariniV. Filipazzi, J. Menis, E. Rizzo, F. Barbieri, E. Rijavec, F. Cecere, G. Spitaleri, E. Bria, S. 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. © 2017 Elsevier Inc.
Original languageEnglish
JournalClinical Lung Cancer
DOIs
Publication statusPublished - 2017

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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

Keywords

  • Erlotinib
  • G719X
  • Gefitinib
  • Heterogeneity outcome
  • L861Q

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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, S.; Rossi, A.; Vavalà, T.; Follador, A.; Tiseo, M.; Galetta, D.; Morabito, A.; Di Maio, M.; Martelli, O.; Caffo, O.; Piovano, P.L.; Cortinovis, D.; Zilembo, N.; Casartelli, C.; Banna, G.L.; Ardizzoia, A.; Barzelloni, M.L.; Bearz, A.; Genestreti, G.; Mucciarini, C.; Filipazzi, V.; Menis, J.; Rizzo, E.; Barbieri, F.; Rijavec, E.; Cecere, F.; Spitaleri, G.; Bria, E.; Novello, S.

In: Clinical Lung Cancer, 2017.

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 2017, '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. https://doi.org/10.1016/j.cllc.2017.05.016
Pilotto, S. ; Rossi, A. ; Vavalà, T. ; Follador, A. ; Tiseo, M. ; Galetta, D. ; Morabito, A. ; Di Maio, M. ; Martelli, O. ; Caffo, O. ; Piovano, P.L. ; Cortinovis, D. ; Zilembo, N. ; Casartelli, C. ; Banna, G.L. ; Ardizzoia, A. ; Barzelloni, M.L. ; Bearz, A. ; Genestreti, G. ; Mucciarini, C. ; Filipazzi, V. ; Menis, J. ; Rizzo, E. ; Barbieri, F. ; Rijavec, E. ; Cecere, F. ; Spitaleri, G. ; Bria, E. ; Novello, S. / 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. 2017.
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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. {\circledC} 2017 Elsevier Inc.",
keywords = "Erlotinib, G719X, Gefitinib, Heterogeneity outcome, L861Q",
author = "S. Pilotto and A. Rossi and T. Vaval{\`a} and A. Follador and M. Tiseo and D. Galetta and A. Morabito and {Di Maio}, M. and O. Martelli and O. Caffo and P.L. Piovano and D. Cortinovis and N. Zilembo and C. Casartelli and G.L. Banna and A. Ardizzoia and M.L. Barzelloni and A. Bearz and G. Genestreti and C. Mucciarini and V. Filipazzi and J. Menis and E. Rizzo and F. Barbieri and E. Rijavec and F. Cecere and G. Spitaleri and E. Bria and S. Novello",
note = "Export Date: 14 July 2017 Article in Press CODEN: CLCLC Correspondence Address: Pilotto, S.email: sara.pilotto@univr.it",
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journal = "Clinical Lung Cancer",
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}

TY - JOUR

T1 - 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

AU - Pilotto, S.

AU - Rossi, A.

AU - Vavalà, T.

AU - Follador, A.

AU - Tiseo, M.

AU - Galetta, D.

AU - Morabito, A.

AU - Di Maio, M.

AU - Martelli, O.

AU - Caffo, O.

AU - Piovano, P.L.

AU - Cortinovis, D.

AU - Zilembo, N.

AU - Casartelli, C.

AU - Banna, G.L.

AU - Ardizzoia, A.

AU - Barzelloni, M.L.

AU - Bearz, A.

AU - Genestreti, G.

AU - Mucciarini, C.

AU - Filipazzi, V.

AU - Menis, J.

AU - Rizzo, E.

AU - Barbieri, F.

AU - Rijavec, E.

AU - Cecere, F.

AU - Spitaleri, G.

AU - Bria, E.

AU - Novello, S.

N1 - Export Date: 14 July 2017 Article in Press CODEN: CLCLC Correspondence Address: Pilotto, S.email: sara.pilotto@univr.it

PY - 2017

Y1 - 2017

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. © 2017 Elsevier Inc.

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. © 2017 Elsevier Inc.

KW - Erlotinib

KW - G719X

KW - Gefitinib

KW - Heterogeneity outcome

KW - L861Q

U2 - 10.1016/j.cllc.2017.05.016

DO - 10.1016/j.cllc.2017.05.016

M3 - Article

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

ER -