Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors following progression with imatinib, sunitinib and regorafenib.

Background: Rechallenge with imatinib is an option in advanced gastrointestinal stromal tumor (GIST) patients following progression with standard tyrosine-kinase inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively collected data from metastatic Italian GIST patients treated with imatinib resumption after progression to conventional TKIs.

Methods: A total of 104 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected from six referral Italian institutions. Mutational analysis was recorded and correlated with survival and response according to RECIST 1.1 or CHOI criteria.

Results: Overall, 71 patients treated with imatinib 400 mg as rechallenge were included. Mutational status was available in all patients. The median follow up was 13 months. In patients who received a rechallenge therapy, the median time to progression (TTP) was 5.4 months [95% confidence interval (CI) 1.9-13.5] and overall survival (OS) was 10.6 months (95% CI 2.8-26.9). A correlation between mutational status, response rate, TTP and OS was not found but comparing deleted versus nondeleted KIT exon 11 patients, a significant difference was identified in terms of TTP and OS ( p  = 0.04 and p  = 0.02, respectively).

Conclusions: Our retrospective data confirm that imatinib rechallenge is a reasonable option in advanced GIST. The prognostic value of the specific KIT mutations was confirmed in our series.