Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer

P A Jänne; I Smith; G McWalter; H Mann; B Dougherty; J Walker; M C M Orr; D R Hodgson; A T Shaw; J R Pereira; G Jeannin; J Vansteenkiste; C H Barrios; F A Franke; L Crinò; P Smith

doi:10.1038/bjc.2015.215

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer

Br J Cancer. 2015 Jul 14;113(2):199-203. doi: 10.1038/bjc.2015.215. Epub 2015 Jun 30.

Authors

P A Jänne¹, I Smith², G McWalter², H Mann², B Dougherty³, J Walker², M C M Orr², D R Hodgson², A T Shaw⁴, J R Pereira⁵, G Jeannin⁶, J Vansteenkiste⁷, C H Barrios⁸, F A Franke⁹, L Crinò¹⁰, P Smith²

Affiliations

¹ Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
² AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
³ AstraZeneca, Gatehouse Park, Waltham, MA 02451, USA.
⁴ Department of Medicine, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114, USA.
⁵ Instituto Brasileiro de Cancerologia Torácica, Rua Dr. Martinico Prado, 26/101, Higienópolis, Sao Paulo 01224-010, Brazil.
⁶ Department of Pneumology, Hôpital Gabriel Montpied, 58 Rue Montalembert, 63000 Clermont-Ferrand, France.
⁷ Department of Pneumology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
⁸ Department of Medicine, PUCRS School of Medicine, Padre Chagas 66, 203, Porto Alegre RS 90 570 080, Brazil.
⁹ CACON, Hospital de Caridade de Ijuí, Avenida David José Martins, 152-Centro, Ijuí RS 98700-000, Brazil.
¹⁰ Department of Oncology, University Medical School Perugia, Piazza Università 1, 06123 Perugia, Italy.

Abstract

Background: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825).

Methods: Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations.

Results: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations.

Conclusion: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Benzimidazoles / administration & dosage
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / mortality
Codon*
Docetaxel
Female
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / mortality
Male
Middle Aged
Mutation*
Neoplasm Staging
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins p21(ras)
Retrospective Studies
Taxoids / administration & dosage
ras Proteins / genetics*

Substances

AZD 6244
Benzimidazoles
Codon
KRAS protein, human
Proto-Oncogene Proteins
Taxoids
Docetaxel
Proto-Oncogene Proteins p21(ras)
ras Proteins

Associated data

ClinicalTrials.gov/NCT00890825