Survival in advanced GIST has improved over time and correlates with increased access to post-imatinib tyrosine kinase inhibitors: results from Life Raft Group Registry.

BACKGROUND

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. However, the impact of these agents on overall survival (OS) is unclear.

METHODS

The 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.

RESULTS

Median 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,  = 0.023, HR 1.377) and 16.8 months for patients who never received sunitinib in any treatment line (n = 42,  = 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,  = 0.0002, HR 2.231), and was longer than that of patients who received any other 3L treatment (19.8 months,  = 0.044, HR 1.525). OS for advanced GIST patients in the LRG registry has improved over time ( = 0.0013), correlated with the increased use of TKIs in ≥ 2L settings.

CONCLUSIONS

In 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.