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 language | English |
|---|---|
| Pages (from-to) | e186-e194 |
| Journal | Clinical Lung Cancer |
| Volume | 20 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 1 2019 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations
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.
KW - Complex mutations
KW - Exon 18
KW - Exon 20
KW - Lung cancer
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85058417112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058417112&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2018.11.005
DO - 10.1016/j.cllc.2018.11.005
M3 - Article
C2 - 30563752
AN - SCOPUS:85058417112
VL - 20
SP - e186-e194
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
SN - 1525-7304
IS - 2
ER -