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

Abstract

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, 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.

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.

Keywords: GIST; Gastrointestinal stromal tumors; Regorafenib; Sunitinib; Survival.

Fig. 1

Flowsheet of outcomes as reported by patients

Fig. 2

2L, 3L and 3L+ comparison groups

Fig. 3

Exploratory analyses of the impact of sunitinib on overall survival. a OS 2nd line, all other drugs group may or may not have had sunitinib later. b OS 2nd line, all other drugs group excludes patients that had sunitinib at a later time

Fig. 4

OS 2nd line sunitinib by start year. The Gehan–Breslow–Wilcoxon test gives more weight to early time points and appears to be more appropriate for this analysis because patients in the Start year < 2006 category that live long enough will have increased access to ≥ 3L drugs and thus potential for increased OS

Fig. 5

OS 3rd line, all other drugs group excludes patients that had regorafenib at a later time. Regorafenib improved overall survival by 11.9 months in 3rd line treatment compared to best supportive care with other TKI’s and excluding no treatment as best supportive care. Patients that had regorafenib in any treatment line were excluded from the all other drugs group. A high percentage of patients in regorafenib group were still alive at last follow-up (censored), suggesting an even greater benefit might be possible. Analysis limited to patients reporting progression in 2nd line

Fig. 6

The effect of TKI access over time on overall survival of GIST patients. a Most commonly used drugs, 3rd line and beyond by year started 3rd line. b OS from start of 3rd line by time period