KIT Status, Tumor Burden Predict Long-term Imatinib Outcomes for Patients with GIST
Genotype, tumor burden, and performance status predict 10-year survival rates among patients with GIST treated with imatinib.
Genotype, tumor burden, and performance status (PS) predict 10-year survival rates among patients with metastatic gastrointestinal stromal tumors (GIST) treated with imatinib, according to a study published in the Journal of Clinical Oncology.1
“With a long follow-up, 6% of patients are long-term progression-free and 13% are survivors,” concluded lead and corresponding study author Paolo G Casali, MD, of the Instituto Nazionale Tumori (National Cancer Institute) in Milano, Italy, and coauthors.
In multivariate analyses, PS, KIT mutation status, and largest tumor size were predictive of long-term survival.
“The main predictive factor for response to imatinib is genotype,” the authors reported. “The main predictive factor for duration of response is tumor burden. No other relevant predictive or prognostic factors seem to exist, according to the best data available today, for long-term survivorship, assuming that good PS and the lack of previous chemotherapy are surrogates for disease burden.”
The study did not, however, involve extensive genomic or immune system testing.
The results were from a randomized clinical trial, initiated in 2001, that compared standard 400 mg daily imatinib dose with 800 mg among patients with locally advanced or metastatic GIST. The trial had a cross-over design, with patients who experienced disease progression on standard dose given the option of doubling their daily imatinib dose to 800 mg.
At a median follow-up of 10.9 years, median progression-free survival (PFS) durations were similar, at 1.7 years among patients in the 400 mg group and 2.0 years among those in the 800 mg group. Median overall survival (OS) was 3.9 years in both study groups.
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At 10 years, PFS and OS rates from the 400 mg group were 9.5% and 19.4%, respectively, comparable to the 800 mg study group's 9.2% and 21.5%, the authors reported.
“Genomic and/or immune profiling could help understand long-term survivorship,” the authors concluded. “Addressing secondary resistance remains a therapeutic challenge.”
- Casali PG, Zalcberg J, Le Cesne A, et al. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol. 2017 Mar 31. doi: 10.1200/JCO.2016.71.0228 [Epub ahead of print]