Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

Antonio Passaro, Arsela Prelaj, Laura Bonanno, Marcello Tiseo, Alessandro Tuzi, Claudia Proto, Rita Chiari, Danilo Rocco, Carlo Genova, Claudio Sini, Diego Cortinovis, Sara Pilotto, Lorenza Landi, Chiara Bennati, Andrea Camerini, Luca Toschi, Carlo Putzu, Giulio Cerea, Gianluca Spitaleri, Federico CappuzzoFilippo de Marinis

Research output: Contribution to journalArticle

Abstract

Background: Molecular characterization of non–small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. Patients and Methods: We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. Results: Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. Conclusion: Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.

Original languageEnglish
Pages (from-to)e186-e194
JournalClinical Lung Cancer
Volume20
Issue number2
DOIs
Publication statusPublished - Mar 1 2019

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Exons
Point Mutation
Protein-Tyrosine Kinases
Survival
Insertional Mutagenesis
Disease-Free Survival

Keywords

  • Complex mutations
  • Exon 18
  • Exon 20
  • Lung cancer
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations. / Passaro, Antonio; Prelaj, Arsela; Bonanno, Laura; Tiseo, Marcello; Tuzi, Alessandro; Proto, Claudia; Chiari, Rita; Rocco, Danilo; Genova, Carlo; Sini, Claudio; Cortinovis, Diego; Pilotto, Sara; Landi, Lorenza; Bennati, Chiara; Camerini, Andrea; Toschi, Luca; Putzu, Carlo; Cerea, Giulio; Spitaleri, Gianluca; Cappuzzo, Federico; de Marinis, Filippo.

In: Clinical Lung Cancer, Vol. 20, No. 2, 01.03.2019, p. e186-e194.

Research output: Contribution to journalArticle

Passaro, A, Prelaj, A, Bonanno, L, Tiseo, M, Tuzi, A, Proto, C, Chiari, R, Rocco, D, Genova, C, Sini, C, Cortinovis, D, Pilotto, S, Landi, L, Bennati, C, Camerini, A, Toschi, L, Putzu, C, Cerea, G, Spitaleri, G, Cappuzzo, F & de Marinis, F 2019, 'Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations', Clinical Lung Cancer, vol. 20, no. 2, pp. e186-e194. https://doi.org/10.1016/j.cllc.2018.11.005
Passaro, Antonio ; Prelaj, Arsela ; Bonanno, Laura ; Tiseo, Marcello ; Tuzi, Alessandro ; Proto, Claudia ; Chiari, Rita ; Rocco, Danilo ; Genova, Carlo ; Sini, Claudio ; Cortinovis, Diego ; Pilotto, Sara ; Landi, Lorenza ; Bennati, Chiara ; Camerini, Andrea ; Toschi, Luca ; Putzu, Carlo ; Cerea, Giulio ; Spitaleri, Gianluca ; Cappuzzo, Federico ; de Marinis, Filippo. / Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations. In: Clinical Lung Cancer. 2019 ; Vol. 20, No. 2. pp. e186-e194.
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AU - Passaro, Antonio

AU - Prelaj, Arsela

AU - Bonanno, Laura

AU - Tiseo, Marcello

AU - Tuzi, Alessandro

AU - Proto, Claudia

AU - Chiari, Rita

AU - Rocco, Danilo

AU - Genova, Carlo

AU - Sini, Claudio

AU - Cortinovis, Diego

AU - Pilotto, Sara

AU - Landi, Lorenza

AU - Bennati, Chiara

AU - Camerini, Andrea

AU - Toschi, Luca

AU - Putzu, Carlo

AU - Cerea, Giulio

AU - Spitaleri, Gianluca

AU - Cappuzzo, Federico

AU - de Marinis, Filippo

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: Molecular characterization of non–small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. Patients and Methods: We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. Results: Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. Conclusion: Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.

AB - Background: Molecular characterization of non–small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. Patients and Methods: We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. Results: Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. Conclusion: Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.

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KW - Exon 18

KW - Exon 20

KW - Lung cancer

KW - Tyrosine kinase inhibitors

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