Format

Send to

Choose Destination
BMC Cancer. 2016 Jan 15;16:22. doi: 10.1186/s12885-016-2051-5.

Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial.

Author information

1
Department of Interdisciplinary Oncology, HELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125, Berlin, Germany. peter.reichardt@helios-kliniken.de.
2
Ludwig Center at Harvard and Dana-Farber Cancer Institute, Boston, MA, USA. george_demetri@dfci.harvard.edu.
3
Leiden University Medical Center, Leiden, The Netherlands. a.j.gelderblom@lumc.nl.
4
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. rutkowskip@coi.waw.pl.
5
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. moisa@snu.ac.kr.
6
Tata Memorial Centre, Mumbai, India. sudeepgupta04@yahoo.com.
7
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. ykkang@amc.seoul.kr.
8
University Hospitals Leuven, Leuven Cancer Institute, and Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium. patrick.schoffski@uz.kuleuven.ac.be.
9
Hämatoonkologische Schwerpunktpraxis, Düsseldorf, Germany. jochen.schuette@uni-duisburg-essen.de.
10
Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada. denis.soulieres@umontreal.ca.
11
Centre Léon Bérard, Université Claude Bernard, Lyon, France. jean-yves.blay@lyon.unicancer.fr.
12
Prince of Wales Hospital, Sydney, Australia. d.goldstein@unsw.edu.au.
13
Pfizer Oncology, Groton, CT, USA. kolette.d.fly@pfizer.com.
14
Pfizer Oncology, La Jolla, CA, USA. xin.huang@pfizer.com.
15
Pfizer Oncology, Milan, Italy. massimo.corsaro@pfizer.com.
16
Pfizer Oncology, Milan, Italy. mariajose.lechuga@pfizer.com.
17
Pfizer Oncology, La Jolla, CA, USA. jean-francois.martini@pfizer.com.
18
VA Portland Health Care System and Oregon Health & Science University, Portland, OR, USA. heinrich@ohsu.edu.

Abstract

BACKGROUND:

Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-α (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population.

METHODS:

This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule. Molecular status was obtained in local laboratories with tumor samples obtained either pre-imatinib, post-imatinib/pre-sunitinib, or post-sunitinib treatment, and all available data were used in the analyses regardless of collection time. The primary analysis compared PFS in patients with primary KIT exon 11 versus exon 9 mutations (using a 2-sided log-rank test) and secondary analyses compared OS (using the same test) and ORR (using a 2-sided Pearson χ(2) test) in the same molecular subgroups.

RESULTS:

Of the 1124 sunitinib-treated patients in the treatment-use study, 230 (20%) were included in this analysis, and baseline characteristics were similar between the two study populations. Median PFS was 7.1 months. A significantly better PFS was observed in patients with a primary mutation in KIT exon 9 (n = 42) compared to those with a primary mutation in exon 11 (n = 143; hazard ratio = 0.59; 95 % confidence interval, 0.39-0.89; P = 0.011), with median PFS times of 12.3 and 7.0 months, respectively. Similarly, longer OS and higher ORR were observed in patients with a primary KIT mutation in exon 9 versus exon 11. The data available were limited to investigate the effects of additional KIT or PDGFRA mutations on the efficacy of sunitinib treatment.

CONCLUSIONS:

This large retrospective analysis confirms the prognostic significance of KIT mutation status in patients with GIST. This analysis also confirms the effectiveness of sunitinib as a post-imatinib therapy, regardless of mutational status.

TRIAL REGISTRATION:

NCT01459757.

PMID:
26772734
PMCID:
PMC4714485
DOI:
10.1186/s12885-016-2051-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center