Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification

A single-arm, phase 2 study

Sung Hee Lim, Jong Mu Sun, Yoon La Choi, Hye Ryun Kim, Soomin Ahn, Ji Yun Lee, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Joo Hang Kim, ByoungChul Cho, Myung Ju Ahn

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS: Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of>5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity. RESULTS: All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%-23.8%) and the disease control rate was 50% (95% CI, 30.8%-69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months,≥5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95% CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95% CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted.

Original languageEnglish
Pages (from-to)3027-3031
Number of pages5
JournalCancer
Volume122
Issue number19
DOIs
Publication statusPublished - 2016 Jun 17

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Receptor, Fibroblast Growth Factor, Type 1
Non-Small Cell Lung Carcinoma
Squamous Cell Neoplasms
Safety
Confidence Intervals
Lung Neoplasms
Disease-Free Survival
Survival
National Cancer Institute (U.S.)
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Hyponatremia
Anorexia
Fluorescence In Situ Hybridization
Oncogenes
Terminology
Fatigue
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lim, Sung Hee ; Sun, Jong Mu ; Choi, Yoon La ; Kim, Hye Ryun ; Ahn, Soomin ; Lee, Ji Yun ; Lee, Se Hoon ; Ahn, Jin Seok ; Park, Keunchil ; Kim, Joo Hang ; Cho, ByoungChul ; Ahn, Myung Ju. / Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification : A single-arm, phase 2 study. In: Cancer. 2016 ; Vol. 122, No. 19. pp. 3027-3031.
@article{f6486f273099498fbdd1b026fca1be3f,
title = "Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification: A single-arm, phase 2 study",
abstract = "BACKGROUND: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS: Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of>5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity. RESULTS: All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5{\%} (95{\%} confidence interval [95{\%} CI], 0.8{\%}-23.8{\%}) and the disease control rate was 50{\%} (95{\%} CI, 30.8{\%}-69.2{\%}), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months,≥5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95{\%} CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95{\%} CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2{\%}), anorexia (11.5{\%}), and hyponatremia (11.5{\%}) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted.",
author = "Lim, {Sung Hee} and Sun, {Jong Mu} and Choi, {Yoon La} and Kim, {Hye Ryun} and Soomin Ahn and Lee, {Ji Yun} and Lee, {Se Hoon} and Ahn, {Jin Seok} and Keunchil Park and Kim, {Joo Hang} and ByoungChul Cho and Ahn, {Myung Ju}",
year = "2016",
month = "6",
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doi = "10.1002/cncr.30135",
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volume = "122",
pages = "3027--3031",
journal = "Cancer",
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}

Lim, SH, Sun, JM, Choi, YL, Kim, HR, Ahn, S, Lee, JY, Lee, SH, Ahn, JS, Park, K, Kim, JH, Cho, B & Ahn, MJ 2016, 'Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification: A single-arm, phase 2 study', Cancer, vol. 122, no. 19, pp. 3027-3031. https://doi.org/10.1002/cncr.30135

Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification : A single-arm, phase 2 study. / Lim, Sung Hee; Sun, Jong Mu; Choi, Yoon La; Kim, Hye Ryun; Ahn, Soomin; Lee, Ji Yun; Lee, Se Hoon; Ahn, Jin Seok; Park, Keunchil; Kim, Joo Hang; Cho, ByoungChul; Ahn, Myung Ju.

In: Cancer, Vol. 122, No. 19, 17.06.2016, p. 3027-3031.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of dovitinib in pretreated patients with advanced squamous non-small cell lung cancer with FGFR1 amplification

T2 - A single-arm, phase 2 study

AU - Lim, Sung Hee

AU - Sun, Jong Mu

AU - Choi, Yoon La

AU - Kim, Hye Ryun

AU - Ahn, Soomin

AU - Lee, Ji Yun

AU - Lee, Se Hoon

AU - Ahn, Jin Seok

AU - Park, Keunchil

AU - Kim, Joo Hang

AU - Cho, ByoungChul

AU - Ahn, Myung Ju

PY - 2016/6/17

Y1 - 2016/6/17

N2 - BACKGROUND: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS: Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of>5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity. RESULTS: All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%-23.8%) and the disease control rate was 50% (95% CI, 30.8%-69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months,≥5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95% CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95% CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted.

AB - BACKGROUND: Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS: Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of>5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity. RESULTS: All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%-23.8%) and the disease control rate was 50% (95% CI, 30.8%-69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months,≥5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95% CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95% CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted.

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