The results of this case report demonstrate that a GIST patient who has undergone adjuvant imatinib therapy responded when rechallenged with imatinib as a treatment for her recurrent disease. These results suggest that sensitivity to imatinib was not compromised by prior exposure to adjuvant imatinib.
The Korean adjuvant Phase II study referred to in this case report enrolled patients with resected primary GIST possessing
KIT exon 11 mutations at high risk of recurrence (mitotic rate ≥5 mitoses/50 HPF and tumor size ≥5 cm, or mitotic rate ≥10 mitoses/50 HPF, or tumor size ≥10 cm) [
9,
10]. Our previous retrospective study showed that the presence of
KIT mutations, along with a high mitotic rate and larger tumor size, was an independent risk factor for poor prognosis in patients with localized GIST [
10]. Because GIST harboring
KIT exon 11 mutations appeared to be more sensitive to imatinib treatment than GIST of other genotypes in the metastatic setting [
11] and, shown more recently, in the adjuvant setting [
12], patients with
KIT exon 11 mutations at high risk of recurrence would be most likely to benefit from adjuvant treatment with imatinib. The fact that some patients, including our patient described in this case report, developed disease recurrence after stopping adjuvant therapy suggests that two years of adjuvant imatinib treatment may not be sufficient for eradicating residual GIST tumor cells and preventing relapse in these high-risk patients. Our patient's residual tumor cells remained sensitive to imatinib therapy, as evidenced by her good response to subsequent imatinib rechallenge. However, it appears that the sensitive residual tumor cells need to be continuously suppressed with adjuvant imatinib therapy to prevent or further delay disease recurrence. The question of how long patients should be treated with adjuvant imatinib remains. The Phase III study conducted by the Scandinavian Sarcoma Group (SSG) and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie (AIO; SSGXVIII/AIO study) recently demonstrated that three years of adjuvant imatinib treatment, compared with one year of imatinib treatment, significantly improves RFS and OS in GIST patients who have a high estimated risk of recurrence after surgery [
13]. This suggests that patients at high risk of recurrence, such as our patient described in this case report, should receive adjuvant imatinib treatment for a minimum duration of three years. This is reflected in the updated National Comprehensive Cancer Network guidelines that, based on the results of the SSGXVIII/AIO trial, recommend considering adjuvant imatinib for at least 36 months for patients with high-risk GIST [
14].
Our patient in this case report remained progression-free for two years and nine months, which is shorter than the median progression-free survival (PFS) of approximately four years achieved in a Korean Phase II study of patients with advanced GIST [
15], but longer than the median PFS of 18 to 20 months reported in other studies of imatinib therapy for metastatic or recurrent GIST [
16]. Although it is not feasible to compare the results of clinical studies conducted in different patient populations at different times, the 33 months of PFS we observed in this case report suggest that our patient maintained sensitivity to imatinib even though she was previously exposed to imatinib for two years in the adjuvant setting.