By Christina Frangou
San Francisco—In a study that affirms a practice widely recommended but never validated, surgeons have shown that patients who undergo surgery to remove residual tumors after imatinib therapy have significantly longer overall and progression-free survival than those who receive imatinib (Gleevec, Novartis) therapy alone.
“Many clinicians think that adding surgery is beneficial to the patient if the patient is responsive to imatinib but clinical evidence for this is very scarce,” said lead author Seong Joon Park, MD, a fellow at Asan Medical Center in Seoul, South Korea.
“This study suggests that surgery offers a substantial survival benefit for patients with metastatic or recurrent GIST [gastrointestinal stromal tumors].”
At the 2013 Gastrointestinal Cancers Symposium, Dr. Park presented results from a retrospective study of 134 patients with metastatic or recurrent GIST who were treated with imatinib alone (n=92) or imatinib plus surgery to remove residential tumor lesions (n=42). All patients were responsive to imatinib for at least six months.
Patients who received surgery plus imatinib had double the progression-free survival of patients who received imatinib alone at 87.7 months versus 42.8 months. Overall survival also was significantly better among patients who received surgery, and patients in the imatinib plus surgery group had a 5.5-fold lower risk for death.
“This study really provides provocative evidence that taking a surgical approach in addition to medical treatment with imatinib may in fact result in longer survival of patients with GI stromal tumors and controls the disease on the order of years,” said Neal Meropol, MD, chief of hematology and oncology at Case Western Reserve University, Cleveland.
Mitchell Posner, MD, Thomas D. Jones Professor and chief of general surgery and surgical oncology, University of Chicago, said the study is “interesting but not groundbreaking” because it is not a randomized trial. The study will not change clinical practice as “almost everyone” is already resecting patients with residual disease or those with tumors that stop responding to imatinib, he said.
Based on previous retrospective trials, most experts agree that patients with GIST benefit from surgical removal of residual tumors. However, the previous studies did not provide sufficient evidence that surgery is beneficial because they assessed clinical outcomes in patients who had received surgery without comparison to patients who did not undergo surgery (J Clin Oncol 2006;24:2325-2331; J Surg Oncol 2008;98:27-33; Ann Oncol 2010;21:403-408).
European investigators recently designed a randomized study to examine this question prospectively. However, the study was terminated because of poor accrual.
In Dr. Park’s study, researchers used several statistical models to correct for
the selection bias inherent in a retrospective study. The models included univariate and multivariate analyses, propensity scores and inverse probability-weighting adjustment. The analyses confirmed that having a low initial tumor burden was associated with longer overall survival. Low initial tumor burden, female gender and a specific alteration in the KIT gene also were associated with delayed disease progression. Patients with this KIT alternation typically have better response to imatinib therapy.
Patients in the surgery group were younger (median age of 51 years vs. 58 years in the imatinib group; P=0.002) and had fewer tumors metastatic to the peritoneum (12 vs. 56; P=0.001). The differences are characteristic of clinical practice, said Dr. Park.
“Surgery is a very aggressive treatment strategy, and it’s often considered and recommended in young patients who have good performance status,” he said. Multiple peritoneal metastases make surgery difficult, he added.