Imatinib Interrupted by Surgery Improves Outcomes for Patients with Metastatic/Recurrent GIST
(ChemotherapyAdvisor) – Patients with metastatic or recurrent gastrointestinal stromal tumors (GIST) who undergo surgical resection of residual lesions after disease control with imatinib have significantly better outcomes compared with those who receive imatinib alone, according to a retrospective analysis presented in advance of the 10th annual Gastrointestinal Cancers Symposium being held January 24-26 in San Francisco, CA.
“Many clinicians think that adding surgery is beneficial to the patient if the patient is responsive to imatinib, but the clinical evidence for this is scarce,” said Seong Joon Park, MD, lead author and a fellow at Asan Medical Center and the University of Ulsan College of Seoul, Seoul, South Korea.
This study, the first controlled trial to address the role of surgery in the treatment of patients with GIST, suggests that surgery offers a substantial survival benefit.
The study included 134 patients who had at least 6 months of disease stabilization or response to imatinib: 42 who had received imatinib interrupted by surgical resection at a median 19.1 months of imatinib treatment (range 7.2–87.0 months) and 92 who received imatinib alone.
Median age was 51 years in the surgical arm and 58 years in the imatinib-alone arm (P=0.002); 12 and 56 patients, respectively, had metastases to the peritoneum (P=0.001). All other patient and tumor characteristics were statistically similar between the two groups.
With a median follow-up of 58.9 months (range 15.4–129.1 months), progression-free survival (PFS) and overall survival were significantly longer in the surgical group (87.7 months and not reached, respectively) than in the imatinib-alone arm (42.8 months and 88.8 months, respectively).
On multivariate analysis, surgical resection of residual lesions as well as female sex, KIT exon II mutation, and low initial tumor burden were associated with longer PFS; surgical resection and low initial tumor burden were associated with longer OS.
To reduce the selection bias, propensity scores and inverse-probability weighting adjustment were applied, which demonstrated the surgical resection arm had significantly better outcome in terms of both PFS (hazard ratio [HR], 2.326; 95% CI: 1.034–5.236; P=0.0412) and OS (HR, 5.464; 95% CI: 1.460–20.408; P=0.0117).
Approximately 80% to 85% of patients with metastatic or recurrent GIST respond to imatinib, with residual tumors believed to contribute to development of resistance to imatinib.
Residual lesions can be surgically removed in about one third of patients, with the decision to perform surgery dependent upon tumor and patient characteristics.
“This treatment strategy is worth trying as a clinical practice, if the medical center is large enough to have an experienced multidisciplinary team and low morbidity and mortality associated with surgery,” Dr. Park said. Although the study design was retrospective, the results provide “good evidence supporting current clinical practice, as this strategy is widely adopted already,” he concluded.
The 2013 Gastrointestinal Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Surgical Oncology (SSO).