GIST patients resistant to imatinib/sunitinib respond to sorafenib

Publication
Article
Oncology NEWS InternationalOncology NEWS International Vol 17 No 4
Volume 17
Issue 4

When GIST patients develop resistance to imatinib (Gleevec), second-line sunitinib (Sutent) has been shown to achieve a response rate of 7% and a median progression-free survival of 6.2 months. When patients progress on sunitinib, however, therapeutic options have been limited.

ORLANDO-When GIST patients develop resistance to imatinib (Gleevec), second-line sunitinib (Sutent) has been shown to achieve a response rate of 7% and a median progression-free survival of 6.2 months. When patients progress on sunitinib, however, therapeutic options have been limited.

University of Chicago investigators reported at the 2008 Gastrointestinal Cancers Symposium (abstract 7) that patients who progressed after treatment with both imatinib and sunitinib responded to sorafenib (Nexavar) 400 mg twice daily.

The multicenter, phase II study has enrolled 26 patients with unresectable c-KIT-expressing GIST, 58% of whom had metastasis to the liver and 73% to the peritoneum. Patients received a median of four 28-day cycles of sorafenib.

Six patients were treated after developing resistance only to imatinib, prior to sunitinib’s approval. Eighteen patients were resistant to both agents.

A partial response was observed in 3 of 24 patients (13%), while 14 patients (58%) achieved stable disease, for a total disease control rate of 71%, reported Halla S. Nimeiri, MD, an oncology fellow at the University of Chicago.

“It is noteworthy that several patients with stable disease experienced a significant improvement in symptoms in the absence of an objective response,” Dr. Nimeiri said.

Median progression-free survival was 5.3 months, median overall survival 13 months, and 1-year survival 62%.

By prior treatment, an exploratory analysis showed that progression-free survival was 3.4 months in patients resistant to just imatinib and 5.3 months for patients resistant to both agents, a nonsignificant difference.

Dose reductions were required by 67% of patients. Grade 3 and 4 toxicities were primarily hand-foot syndrome (28%), hypertension (24%), and rash (20%). The study is continuing to accrue patients.

“It is marvelous how many new agents are available for patients with GIST today,” commented Paolo G. Casali, MD, Donald L. Bren Professor of Medicine, Molecular Biology and Biochemistry, and Director of the Center for Immunology, University of California, Irvine.

“What is emerging is the possibility of extending survival by moving through several lines of therapy,” Dr. Casali said.

Based on Dr. Nimeiri’s findings and those of the Z9000 trial of adjuvant imatinib (see story above), he said, “one might give imatinib for 2 years, and upon resistance, sunitinib will add another 6 months progression-free survival. Upon further progression, sorafenib will add another 5 months.” He called this a vast improvement over a median survival of less than 3 years with surgery alone.

Related Videos
Immunotherapy may be an “elegant” method of managing colorectal cancer, says Gregory Charak, MD.
Administering neoadjuvant therapy to patients with colorectal cancer may help surgical oncologists attain a negative-margin resection.
Increasing screening for younger individuals who are at risk of colorectal cancer may help mitigate the rising early incidence of this disease.
Laparoscopy may reduce the degree of pain or length of hospital stay compared with open surgery for patients with colorectal cancer.
Rahul Gosain, MD; Sam Klempner, MD; and Rohit Gosain, MD, presenting slides
Rahul Gosain, MD; Sam Klempner, MD; and Rohit Gosain, MD, presenting slides
Rahul Gosain, MD; Sam Klempner, MD; and Rohit Gosain, MD, presenting slides
Rahul Gosain, MD; Sam Klempner, MD; and Rohit Gosain, MD, presenting slides
Rahul Gosain, MD; Sam Klempner, MD; and Rohit Gosain, MD, presenting slides
Tailoring neoadjuvant therapy regimens for patients with mismatch repair deficient gastroesophageal cancer represents a future step in terms of research.
Related Content