The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma

H. R. Kim, S. M. Lim, H. J. Kim, S. K. Hwang, J. K. Park, E. Shin, M. K. Bae, S. H.I. Ou, J. Wang, S. S. Jewell, D. R. Kang, R. A. Soo, H. Haack, J. H. Kim, H. S. Shim, B. C. Cho

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Abstract

Background: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. Patients and methods: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. Results: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). Conclusions: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

Original languageEnglish
Article numbermdt220
Pages (from-to)2364-2370
Number of pages7
JournalAnnals of Oncology
Volume24
Issue number9
DOIs
Publication statusPublished - 2013 Sep 1

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Epidermal Growth Factor Receptor
Pemetrexed
Adenocarcinoma of lung
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Protein-Tyrosine Kinases
Disease-Free Survival
Smoking
Mutation
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Kim, H. R. ; Lim, S. M. ; Kim, H. J. ; Hwang, S. K. ; Park, J. K. ; Shin, E. ; Bae, M. K. ; Ou, S. H.I. ; Wang, J. ; Jewell, S. S. ; Kang, D. R. ; Soo, R. A. ; Haack, H. ; Kim, J. H. ; Shim, H. S. ; Cho, B. C. / The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma. In: Annals of Oncology. 2013 ; Vol. 24, No. 9. pp. 2364-2370.
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title = "The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma",
abstract = "Background: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. Patients and methods: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. Results: Of 208 tumors screened, 7 (3.4{\%}) were ROS1 rearranged, and 15 (7.2{\%}) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7{\%} (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0{\%} versus 8.5{\%}; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). Conclusions: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.",
author = "Kim, {H. R.} and Lim, {S. M.} and Kim, {H. J.} and Hwang, {S. K.} and Park, {J. K.} and E. Shin and Bae, {M. K.} and Ou, {S. H.I.} and J. Wang and Jewell, {S. S.} and Kang, {D. R.} and Soo, {R. A.} and H. Haack and Kim, {J. H.} and Shim, {H. S.} and Cho, {B. C.}",
year = "2013",
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doi = "10.1093/annonc/mdt220",
language = "English",
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Kim, HR, Lim, SM, Kim, HJ, Hwang, SK, Park, JK, Shin, E, Bae, MK, Ou, SHI, Wang, J, Jewell, SS, Kang, DR, Soo, RA, Haack, H, Kim, JH, Shim, HS & Cho, BC 2013, 'The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma', Annals of Oncology, vol. 24, no. 9, mdt220, pp. 2364-2370. https://doi.org/10.1093/annonc/mdt220

The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma. / Kim, H. R.; Lim, S. M.; Kim, H. J.; Hwang, S. K.; Park, J. K.; Shin, E.; Bae, M. K.; Ou, S. H.I.; Wang, J.; Jewell, S. S.; Kang, D. R.; Soo, R. A.; Haack, H.; Kim, J. H.; Shim, H. S.; Cho, B. C.

In: Annals of Oncology, Vol. 24, No. 9, mdt220, 01.09.2013, p. 2364-2370.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma

AU - Kim, H. R.

AU - Lim, S. M.

AU - Kim, H. J.

AU - Hwang, S. K.

AU - Park, J. K.

AU - Shin, E.

AU - Bae, M. K.

AU - Ou, S. H.I.

AU - Wang, J.

AU - Jewell, S. S.

AU - Kang, D. R.

AU - Soo, R. A.

AU - Haack, H.

AU - Kim, J. H.

AU - Shim, H. S.

AU - Cho, B. C.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Background: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. Patients and methods: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. Results: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). Conclusions: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

AB - Background: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. Patients and methods: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. Results: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). Conclusions: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

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U2 - 10.1093/annonc/mdt220

DO - 10.1093/annonc/mdt220

M3 - Article

C2 - 23788756

AN - SCOPUS:84883343307

VL - 24

SP - 2364

EP - 2370

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 9

M1 - mdt220

ER -