Surgery Is Beneficial Even When GIST Responds to Imatinib

Zosia Chustecka

January 23, 2013

Surgery offers a substantial survival benefit for patients with metastatic or recurrent gastrointestinal stromal tumors (GIST) who are responding to treatment with imatinib (Gleevec). In fact, this survival is significantly better than in patients who continue taking imatinib but who do not undergo resection.

These results, from a retrospective study of 134 patients, provide clinical evidence for a strategy that is already commonly used in clinical practice, said lead researcher Seong Joon Park, MD, a fellow at Asan Medical Center in Seoul, South Korea.

Dr. Park was speaking at a presscast organized by the American Society of Clinical Oncology, one of several professional societies supporting the 2013 Gastrointestinal Cancers Symposium, being held January 24 to 26 in San Francisco, California.

The data were described as "provocative" by Neal Meropol, MD, chief of the division of hematology and oncology at Case Western Reserve University in Cleveland, Ohio, who moderated the presscast.

Imatinib has an extremely high response rate and controls the disease in the order of years, he said. "This study provides provocative evidence that taking an aggressive approach surgically in addition to medical treatment with imatinib may result in even longer survival for patients with GIST," he noted.

Adding Surgery Is Beneficial

Imatinib is typically the first-line treatment for metastatic or recurrent GIST, and about 80% to 85% of patients respond, Dr. Park explained. However, most patients eventually develop resistance to the drug, and complete remission is rare. Even when patients are responding to imatinib, they have residual tumor lesions, which are thought to contribute to the development of drug resistance. It makes sense that surgically removing these residual tumors would improve survival.

It has been the consensus among experts that adding surgery to imatinib therapy is beneficial, but "the clinical evidence for this is very scare," Dr. Park said. Previous retrospective studies have followed only patients who underwent surgery, whereas this study compared patients who underwent surgery with those who did not.

In their study, 92 patients continued taking imatinib and 42 patients took imatinib but also underwent surgery to remove residual tumor lesions. Patients in the surgery group were younger and had smaller tumors; these clinical characteristics reflect clinical practice, Dr. Park reported.

Not all patients can be resected, but surgery to remove residual tumor lesions can be performed in about a third of patients, he said.

Significantly Better Outcomes

Patients who underwent surgery had significantly better outcomes than those who did not (median progression-free survival, 87.7 vs 42.8 months; = .001). Median overall survival has not yet been reached in the surgery group, but is 88.8 months with imatinib alone (P = .001).

To correct for selection bias, the researchers used several statistical models, including univariate and multivariate analysis and inverse probability of treatment weighting (IPTW). Even after adjustment for IPTW, the outcomes were significantly better in the surgery group, where risk for death was 5.5 times lower.

"This study strongly suggests that surgical resection of the residual lesion after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST," Dr. Park concluded.

Such surgery is worth trying in clinical practice if the medical center is large enough to have an experienced multidisciplinary team and to have low morbidity and mortality rates associated with surgery, he added.

Dr. Parks has disclosed no relevant financial relationships. Dr. Meropol reports acting as a consultant for Precision Therapeutics.

2013 Gastrointestinal Cancers Symposium (GICS): Abstract 62. To be presented January 24, 2013.