Dataset Information

Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for Treatment With Ponatinib.

ABSTRACT:

Introduction

Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines. KRAS mutations did not preclude sensitivity.

Patients and methods

Metastatic EGFR- and ALK-negative lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hybridization (SISH). Patients with positive findings were offered ponatinib, a multi-kinase inhibitor of FGFR1-4. Differences in overall survival (OS) between cohorts were assessed by the log-rank test. Association of FGFR1 positivity with clinicopathologic features were assessed by Fisher exact test and Kruskal-Wallis rank sum test.

Results

A total of 171 cases were prescreened: 9 (7.3%) of 123 SISH⁺; 53 (42.1%) of 126 ISH⁺; and 6 cases concordantly positive for SISH and ISH. SISH⁺ cases had fewer coincident KRAS mutations (P = .03) than SISH^- cases, and ISH⁺ cases had worse OS (P = .020) than ISH^- cases. Data distributions suggested a distinct higher positivity cut point for FGFR1 ISH (≥ 20%), occurring in 29 (23%) of 126 cases, was associated with small-cell lung cancer histology (P = .022), soft tissue metastases (P = .050) and shorter OS (P = .031). Four patients received ponatinib on study: All ISH⁺ by the initial cut point, 2 of 4 by higher cut point, 1 of 4 SISH⁺. Tolerability was poor. The best response for the 2 higher ISH cases was stable disease and progressive disease for the 2 lower ISH cases.

Conclusion

Elevated FGFR1-MRNA is more common than FGFR1-AMP and associated with worse OS. Higher FGFR1 mRNA expression may be associated with a specific phenotype and is worthy of further exploration. Ponatinib's poor tolerance suggests further fibroblast growth factor receptor exploration in ISH⁺ cases should utilize more selective FGFR1 inhibitors.

SUBMITTER: Ng TL

PROVIDER: S-EPMC6339510 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for Treatment With Ponatinib.

Ng Terry L TL Yu Hui H Smith Derek E DE Boyle Theresa A TA York Emily R ER Leedy Scott S Gao Dexiang D Aisner Dara L DL Van Bokhoven Adrie A Heasley Lynn E LE Hirsch Fred R FR Camidge D Ross DR

Clinical lung cancer 20180907 1

<h4>Introduction</h4>Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines. KRAS mutations did not preclude sensitivity.<h4>Patients and methods</h4>Metastatic EGFR- and ALK-negative lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hy ...[more]

PMID: 30297175

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Dataset Information

Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for Treatment With Ponatinib.

Introduction

Patients and methods

Results

Conclusion

Publications

Preselection of Lung Cancer Cases Using FGFR1 mRNA and Gene Copy Number for Treatment With Ponatinib.

Similar Datasets

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