Abstract
BackgroundThe use of imatinib, sunitinib, and regorafenib has transformed the treatment of advanced GIST. Sunitinib and regorafenib improve progression free-survival in the second (2L) and third (3L) line, respectively, compared with placebo. However, the impact of these agents on overall survival (OS) is unclear.MethodsThe Life Raft Group (LRG) patient registry contains records from 1716 GIST patients; 526 have advanced to at least 2L treatment. Patient-reported treatment and outcome data were examined to determine treatment patterns and their impact on OS.ResultsMedian OS from start of 2L therapy was 32.4 months for sunitinib (n = 436) compared with 27.1 months for patients treated with any other 2L drug (n = 74, p = 0.023, HR 1.377) and 16.8 months for patients who never received sunitinib in any treatment line (n = 42, p = 0.028, HR 1.52). In patients reporting progression in 2L, the median OS in patients subsequently receiving 3L regorafenib (n = 53, 26.2 months) was longer than that of 3L patients who never received regorafenib in any line of therapy (n = 174, 14.3 months, p = 0.0002, HR 2.231), and was longer than that of patients who received any other 3L treatment (19.8 months, p = 0.044, HR 1.525). OS for advanced GIST patients in the LRG registry has improved over time (p = 0.0013), correlated with the increased use of TKIs in ≥ 2L settings.ConclusionsIn our analysis, sunitinib and regorafenib significantly improved OS compared with patients who never received these agents. Our data also support the hypothesis that the use of KIT/PDGFRA inhibitors, including non-approved agents, has improved OS for patients with imatinib- and sunitinib-resistant GIST.
Highlights
The use of imatinib, sunitinib, and regorafenib has transformed the treatment of advanced gastrointestinal stromal tumors (GIST)
Study design and statistical methods In this article, we report on overall survival (OS) and self-reported progression-free survival of patients in the registry, with a focus on 2nd line (2L) and 3rd line (3L) treatments (Fig. 2a–c)
When we replaced the known/unknown variable with the actual mutation the results were similar (Additional file 1: Table S7) with the exception of gender and unknown mutation which both lost significance (p = 0.14 and p = 0.192). These results suggest that the use of nilotinib and/or sorafenib in 3L or 3L+ treatment lines improved survival over imatinib, and that the use of 3L regorafenib was associated with improved OS compared with use of nilotinib and/or sorafenib
Summary
The use of imatinib, sunitinib, and regorafenib has transformed the treatment of advanced GIST. Sunitinib and regorafenib improve progression free-survival in the second (2L) and third (3L) line, respectively, compared with placebo. Gastrointestinal stromal tumors are soft tissue sarcomas that arise from interstitial cells of Cajal (ICC) or from stem cells that can differentiate towards ICCs. GIST have a reported incidence of approximately 14.5 per million per year [1]. Primary tumors most commonly originate in the stomach or intestines and frequently metastasize to the liver or the peritoneum [2, 3]. Imatinib is approved for first line (1L) therapy for advanced/metastatic GIST and for adjuvant treatment after surgery. Sunitinib is approved after progression on or intolerance to imatinib [7]. Regorafenib is approved for patients previously treated with imatinib and sunitinib [8, 9]
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