What question did this study set out to answer?

To evaluate intrapatient molecular and histologic resistance mechanisms—such as EGFR-T790M mutations, MET amplification, and small cell transformation—in lung cancer patients progressing on EGFR-targeted therapy.

October 9, 2019American Journal of Clinical Oncology

Intrapatient Molecular and Histologic Heterogeneity After First-generation or Second-generation TKI Therapy of NSCLC Patients

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Authors

DIDaniela IaconoUniversity of Campania "Luigi Vanvitelli"GOGiorgia Amira OsmanAzienda Ospedaliera Sant'Andrea MMMaria Rita MigliorinoNini Hospital

Discussion

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Implication

Cohort study reveals frequent molecular and histologic heterogeneity in EGFR-mutated lung cancer after targeted therapy, highlighting challenges for subsequent treatment selection.

Key Points

To evaluate intrapatient molecular and histologic resistance mechanisms—such as EGFR-T790M mutations, MET amplification, and small cell transformation—in lung cancer patients progressing on EGFR-targeted therapy.
Analyzed paired pre- and post-TKI tumor biopsies from 27 patients with activating EGFR mutations.
Assessed specimens for acquired EGFR-T790M mutations, MET gene amplification, and histologic shift to small cell lung cancer (SCLC).
Acquired EGFR-T790M mutations were detected in 16 of 27 patients (59%), while MET gene amplification was found in 2 of 19 evaluated cases (10.5%).
Histologic transformation from adenocarcinoma to SCLC occurred in 3 patients (11%), with 1 patient subsequently reverting back to adenocarcinoma.
Spatial and temporal discordance was observed, including mixed T790M positivity across synchronous lesions and longitudinal gains or losses of T790M across sequential biopsies in 4 patients.

Cite This Study

Iacono et al. (2019) studied this question.

synapsesocial.com/papers/6a8683d4cb9e3399d743848c https://doi.org/10.1097/coc.0000000000000615

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Implication

Cohort study reveals frequent molecular and histologic heterogeneity in EGFR-mutated lung cancer after targeted therapy, highlighting challenges for subsequent treatment selection.

Intrapatient Molecular and Histologic Heterogeneity After First-generation or Second-generation TKI Therapy of NSCLC Patients

Discussion

Member takes

Implication

Key Points

Cite This Study

Intrapatient Molecular and Histologic Heterogeneity After First-generation or Second-generation TKI Therapy of NSCLC Patients

Discussion

Member takes

Implication

Key Points

Cite This Study

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