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RESEARCH PRODUCT

Rechallenge in advanced GIST progressing to imatinib, sunitinib and regorafenib: An Italian survey.

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11038 Background: We retrospectively collected data from metastatic Italian GIST patients treated with imatinib or sunitinib reintroduction after progression to conventional three or four lines of therapy. Methods: 82 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected in the present analysis from 6 cancer centres. All patients received all three standard kinase inhibitors. Imatinib dose increase as active second line or 800 mg upfront in exon 9 mutant GIST were allowed. Specific mutations were recorded if available (deletion versus others) and correlated with survival and response according to RECIST 1.1 or CHOI criteria. Results: Seventy-four of 82 patients received Imatinib 400 mg as rechallenge, while 8 patients were treated with sunitinib at personalised dose and schedule according to the physician’s choice. Mutational status was available in all patients and in 68 patients details about type of mutation were achievable. The median follow-up was 13 months (range 1-42 months). The median time to progression (TTP) in patients receiving a rechallenge therapy was 5.4 months (95% CI 1.9-13.5) and Overall Survival (OS) was 10.6 months (95% CI 2.8-26.9). Apparently, in this setting a correlation between mutational status and response rate, TTP or OS was not found. On the contrary, considering only exon 11 mutated patients and comparing patients with deletion vs non deleted ones a significant difference was identified both in terms of TTP and OS (respectively, P = 0.04 and P = 0.02). Conclusions: Our retrospective data confirm that the rechallenge of imatinib or sunitinib is a reasonable option in advanced GIST patients after failure of previous treatments. As expected, imatinib is the most frequently prescribed option in the Italian real-life setting, demonstrating a TTP and OS longer than those observed in previous studies. Also the prognostic value of the specific type of exon 11 KIT mutations has been confirmed in our series.