Surgery after imatinib improved survival for patients with metastatic, recurrent GIST

Issue: February 25, 2013

Patients with metastatic or recurrent gastrointestinal stromal tumors who underwent surgery following imatinib therapy demonstrated significantly improved OS and PFS compared with patients who received imatinib therapy alone, according to results of a retrospective study presented at the Gastrointestinal Cancers Symposium.

Perspective from Dale Shepard, MD, PhD; Neal J. Meropol, MD

Gastrointestinal stromal tumors (GIST) frequently form in the stomach and small intestine.

The targeted tyrosine kinase inhibitor imatinib (Gleevec, Novartis) typically is used as the first-line treatment for metastatic or recurrent GIST. Up to 85% of patients respond to imatinib, but many have residual tumors lesions despite continued treatment.

Residual lesions — believed to contribute to the development of imatinib resistance — can be removed in about one-third of patients with GIST. The benefits of such surgery are unclear, however, because prior studies assessed outcomes only in patients who received surgery, according to background information provided by researchers.

“In this study, we were trying to compare the outcomes of surgical resection of residual lesions after imatinib therapy with those of imatinib therapy alone,” Seong Joon Park, MD, a fellow at Asan Medical Center in Seoul, South Korea, said during a press conference prior to the symposium.

Park and colleagues evaluated 134 patients with metastatic or recurrent GIST who demonstrated at least 6 months of disease stabilization or response to imatinib. Of them, 42 underwent surgery and 92 received imatinib therapy alone. The patients who underwent surgery received a median 19.1 months of imatinib treatment.

Median follow-up was 58.9 months.

Patients who underwent surgery demonstrated significantly longer PFS (87.7 months vs. 42.8 months; P=.001) and OS (not reached vs. 88.8 months; P=.001) than patients who received imatinib alone, according to study results.

After inverse probability weighting adjustment, researchers continued to observe significantly better PFS (HR=2.33; 95% CI, 1.03-5.24) and OS (HR=5.46; 95% CI, 1.46-20.408) for patients who underwent surgery.

“This study suggests that surgery offers a substantial survival benefit for metastatic or recurrent GIST,” Park said.

The decision to perform surgery is dependent on tumor size and patient characteristics, Park said. Park and colleagues also confirmed that low initial tumor burden, female sex and a specific alteration in the KIT gene were associated with delayed disease progression.

For more information:

Park SJ. Abstract #62. Presented at: Gastrointestinal Cancers Symposium; Jan. 24-26, 2013; San Francisco.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Dale Shepard, MD, PhD

The role of imatinib in the neoadjuvant, adjuvant and metastatic setting has been well established, as has the role of surgery for definitive therapy. Unfortunately, most patients with metastatic or recurrent disease develop resistance to imatinib and tumor progression. Unlike some tumors, the role of surgery for residual or metastatic disease for patients with GIST has not been determined. A phase 3 cooperative group trial anticipated enrolling 350 patients to determine the effect of surgery on PFS in patients with residual disease after imatinib. Unfortunately, this was closed due to poor accrual. Although retrospective, the trial discussed here showing improvement in both PFS and OS suggests that discussion of surgery in patients with residual disease after imatinib for metastatic or recurrent disease is appropriate.

Dale Shepard, MD, PhD

Staff physician, department of solid tumor oncology

Taussig Cancer Institute

Cleveland Clinic

Disclosures: Shepard reports no relevant financial disclosures.

Perspective

Neal J. Meropol, MD

Gastrointestinal stromal tumors are an uncommon type of gastrointestinal tumor that can arise within many different places in the gastrointestinal tract. Imatinib is a drug that targets against a particular molecular abnormality present in GIST. As such, it has an extremely high response proportion in patients with GIST. Unfortunately, resistance ultimately develops with imatinib. This study provides provocative evidence that taking an aggressive approach surgically — in addition to treatment with imatinib — may result in even longer survival of patients with GIST.

Neal J. Meropol, MD

Chief of hematology and oncology

Case Western Reserve University School of Medicine and University Hospital

Disclosures: