Abstract
OBJECTIVES: The discovery of tyrosine kinase inhibitors (TKI) has remarkably improved the clinical course of patients with non-small cell lung cancer driven by Epidermal Growth Factor Receptor (EGFR) mutations. However, virtually in all cases, the disease resurfaces in a TKI-resistant form that is mainly linked to an acquired EGFR-T790M mutation, a MET amplification, or small cell lung cancer (SCLC) transformation. Third-generation TKIs are able to block tumor growth through an irreversible binding to the T790M-mutated receptor. Such new treatments require the diagnostic analysis of new pathologic tissue or a liquid biopsy to detect the presence of the T790M mutation. MATERIALS AND METHODS: Pre-TKI and post-TKI biopsies from 27 patients with an activating EGFR mutation were collected and analyzed for EGFR-T790M mutation, MET amplification, and SCLC transformation. RESULTS: The T790M mutation was found in 16 patients (59%) whereas MET gene amplification was found in 2 (10.5%) of 19 evaluated cases. The histologic transformation from adenocarcinoma (ADC) to SCLC was identified in 3 patients (11%). In one of them reversal from SCLC back to adenocarcinoma was observed. One patient had the T790M mutation concordantly detected in 2 synchronous lesions whereas another patient showed T790M positivity only in one of 2 specimens. In 4 patients longitudinal biopsies revealed T790M gains and losses not always according to biological expectations. CONCLUSIONS: Intrapatient molecular or histologic heterogeneity may be frequently found during routine treatment of non-small cell lung cancer patients. This biological aspect may have profound repercussions on subsequent therapeutic decisions, and therefore requires in-depth investigation.
| Original language | English |
|---|---|
| Pages (from-to) | 845-850 |
| Number of pages | 6 |
| Journal | American Journal of Clinical Oncology |
| Volume | 42 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2019 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Intrapatient Molecular and Histologic Heterogeneity After First-generation or Second-generation TKI Therapy of NSCLC Patients : Potential Clinical Impact on Subsequent third-generation TKI Treatment. / Iacono, Daniela; Osman, Giorgia A.; Migliorino, Maria R.; Grillo, Lucia; Remotti, Daniele; Nunnari, Josè; Ricciardi, Serena; Rossi, Antonio; Mancuso, Andrea; Graziano, Paolo; Di Lorenzo, Angela; Bronzini, Monica; Signora, Mauro; Leone, Alvaro.
In: American Journal of Clinical Oncology, Vol. 42, No. 11, 01.11.2019, p. 845-850.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intrapatient Molecular and Histologic Heterogeneity After First-generation or Second-generation TKI Therapy of NSCLC Patients
T2 - Potential Clinical Impact on Subsequent third-generation TKI Treatment
AU - Iacono, Daniela
AU - Osman, Giorgia A.
AU - Migliorino, Maria R.
AU - Grillo, Lucia
AU - Remotti, Daniele
AU - Nunnari, Josè
AU - Ricciardi, Serena
AU - Rossi, Antonio
AU - Mancuso, Andrea
AU - Graziano, Paolo
AU - Di Lorenzo, Angela
AU - Bronzini, Monica
AU - Signora, Mauro
AU - Leone, Alvaro
PY - 2019/11/1
Y1 - 2019/11/1
N2 - OBJECTIVES: The discovery of tyrosine kinase inhibitors (TKI) has remarkably improved the clinical course of patients with non-small cell lung cancer driven by Epidermal Growth Factor Receptor (EGFR) mutations. However, virtually in all cases, the disease resurfaces in a TKI-resistant form that is mainly linked to an acquired EGFR-T790M mutation, a MET amplification, or small cell lung cancer (SCLC) transformation. Third-generation TKIs are able to block tumor growth through an irreversible binding to the T790M-mutated receptor. Such new treatments require the diagnostic analysis of new pathologic tissue or a liquid biopsy to detect the presence of the T790M mutation. MATERIALS AND METHODS: Pre-TKI and post-TKI biopsies from 27 patients with an activating EGFR mutation were collected and analyzed for EGFR-T790M mutation, MET amplification, and SCLC transformation. RESULTS: The T790M mutation was found in 16 patients (59%) whereas MET gene amplification was found in 2 (10.5%) of 19 evaluated cases. The histologic transformation from adenocarcinoma (ADC) to SCLC was identified in 3 patients (11%). In one of them reversal from SCLC back to adenocarcinoma was observed. One patient had the T790M mutation concordantly detected in 2 synchronous lesions whereas another patient showed T790M positivity only in one of 2 specimens. In 4 patients longitudinal biopsies revealed T790M gains and losses not always according to biological expectations. CONCLUSIONS: Intrapatient molecular or histologic heterogeneity may be frequently found during routine treatment of non-small cell lung cancer patients. This biological aspect may have profound repercussions on subsequent therapeutic decisions, and therefore requires in-depth investigation.
AB - OBJECTIVES: The discovery of tyrosine kinase inhibitors (TKI) has remarkably improved the clinical course of patients with non-small cell lung cancer driven by Epidermal Growth Factor Receptor (EGFR) mutations. However, virtually in all cases, the disease resurfaces in a TKI-resistant form that is mainly linked to an acquired EGFR-T790M mutation, a MET amplification, or small cell lung cancer (SCLC) transformation. Third-generation TKIs are able to block tumor growth through an irreversible binding to the T790M-mutated receptor. Such new treatments require the diagnostic analysis of new pathologic tissue or a liquid biopsy to detect the presence of the T790M mutation. MATERIALS AND METHODS: Pre-TKI and post-TKI biopsies from 27 patients with an activating EGFR mutation were collected and analyzed for EGFR-T790M mutation, MET amplification, and SCLC transformation. RESULTS: The T790M mutation was found in 16 patients (59%) whereas MET gene amplification was found in 2 (10.5%) of 19 evaluated cases. The histologic transformation from adenocarcinoma (ADC) to SCLC was identified in 3 patients (11%). In one of them reversal from SCLC back to adenocarcinoma was observed. One patient had the T790M mutation concordantly detected in 2 synchronous lesions whereas another patient showed T790M positivity only in one of 2 specimens. In 4 patients longitudinal biopsies revealed T790M gains and losses not always according to biological expectations. CONCLUSIONS: Intrapatient molecular or histologic heterogeneity may be frequently found during routine treatment of non-small cell lung cancer patients. This biological aspect may have profound repercussions on subsequent therapeutic decisions, and therefore requires in-depth investigation.
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UR - http://www.scopus.com/inward/citedby.url?scp=85074111676&partnerID=8YFLogxK
U2 - 10.1097/COC.0000000000000615
DO - 10.1097/COC.0000000000000615
M3 - Article
C2 - 31644442
AN - SCOPUS:85074111676
VL - 42
SP - 845
EP - 850
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
IS - 11
ER -