What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

Abstract

The introduction of imatinib to clinical practice revolutionized therapy of advanced gastrointestinal stromal tumors (GIST), but its long-term results have been only just collected. We have attempted to identify factors related to the long-term survival. We have analyzed the data of 430 inoperable/metastatic/recurrent GIST patients treated with imatinib in reference centers, assessed the factors influencing the long-term overall survival (OS), and compared the outcomes in three periods of initiation of imatinib therapy during one decade (2001–2003, 2004–2006, 2007–2010). During analyzed time periods, we have found decrease in median largest tumor size at the start of imatinib therapy: 90.5 mm (2001–2003) versus 74 mm (2004–2006) versus 58 mm (2007–2010) (p = 0.002). Median progression-free survival (PFS) on 1st line imatinib was 37.5 months, without differences in PFS between three groups. Median OS was 5.8 years, 8-year OS rate was 43 %, and no difference in OS was demonstrated for patients treated in analyzed time periods. Independent good prognostic factors for longer OS were as follows: surgery of residual disease, initial WHO performance status 0/1, normal baseline albumin level, and the presence of exon 11 KIT mutations. Current median OS in advanced GIST reaches 6 years. The long-term survivors were characterized by smaller maximal tumors at imatinib start, better blood tests results, better performance status, and the surgical removal of residual disease. The latter might reduce the impact of tumor size and equalize the long-term results of therapy during last decade from introduction of imatinib. After introduction of subsequent lines of therapy (as sunitinib), the effect of primary mutational status on the long-term OS is also less visible.

Prediction of long-term survival in patients with metastatic gastrointestinal stromal tumor: analysis of a large, single-institution cohort

“…Patients with large tumors had inferior survival in our study, and previous studies have also shown that a high maximum tumor diameter is associated with shorter PFS [7,13,14]. The most important IM resistance mechanism is the occurrence of secondary KIT mutations [15], and time to IM resistance is closely related to OS.…”

“…In a single-institution study from Taiwan, good performance status, absence of primary IM resistance and small tumor volume was associated with longer OS [14]. A nationwide study from Poland reported that long-term survivors were characterized by small maximum tumor diameter at IM start, better hematological and clinical chemistry parameters, good performance status, and surgical removal of residual disease [13].…”

“…In clinical trials, resistance to IM has occurred at a median time of 18-26 months [7,12]. Studies in real-life practice show a median progression free survival (PFS) of 30-40 months [8,13,14]. Treatment resistance is usually caused by secondary KIT mutations [15], and time to development of TKI-resistant disease is probably a key determinant of survival.…”

Long‐term survival outcome with tyrosine kinase inhibitors and surgical intervention in patients with metastatic or recurrent gastrointestinal stromal tumors: A 14‐year, single‐center experience

“…These are also numerically higher than the 8‐ and 10‐year OS rate of 31% and 23% in the SWOG trial and 10‐year OS rate of 19.4% in the EORTC trial. Consistent with early imatinib trials and recent studies, the long‐term survivors of our study are characterized by younger age, smaller tumor size at the initiation of imatinib, and the presence of exon 11 mutation. Among 126 patients in period 1 with follow‐up >10 years, 42 patients (33.3%) were alive for more than 10 years at the time of the analysis.…”

“…Comparisons between early imatinib trials, recent studies (registered until 2010 or 2013), and the present study are summarized in Table . Although baseline demographic features and KIT or PDGFRA exon mutation were similar between studies, there were differences in tumor burden and surgical intervention.…”