Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo City, Japan
Takahito Awatsu , Hidekazu Hirano , Kunihito Matsuguma , Toshiharu Hirose , Natsuko Tsuda Okita , Hirokazu Shoji , Atsuo Takashima , Ken Kato
Background: Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor arising from the gastrointestinal tract, characterized by a high predominance of the elderly population. Imatinib is the standard first-line therapy for advanced GIST with a median survival of around 4 years in pivotal clinical trials. However, clinical data for the elderly population is not known well. The aim of this study is to evaluate the efficacy and safety of imatinib for advanced GIST in the elderly population in comparison with the non-elderly population. Methods: We extracted clinical data of patients with advanced GIST treated with imatinib as first-line therapy at our institution between January 2010 and July 2023. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events (AEs) were assessed and compared between the elderly group (age: ≥ 70 years, E group) and the non-elderly group (age: < 70 years, NE group). Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of age groups. Results: A total of 91 patients were included in this analysis with 32 patients in the E group and 59 patients in the NE group with a median follow-up duration of 39.8 months. Patient characteristics were as follows (the E group vs. the NE group): median age 76 (70–90) vs. 54 (29–69) years, male: 50% vs. 56%, performance status 0: 19% vs. 63%, disease status (: 47% vs. 44%), stomach primary 44% vs. 34%, KIT mutation (exon 11: 50% vs. 61%), and maximum tumor diameter (≥8cm: 66% vs. 51%). The proportion of patients with a reduced starting dose of imatinib was significantly higher in the E group (34% vs. 2%, p <0.0001). Median PFS in the E group and the NE group were 29.4 months and 60.0 months (HR=2.04, log-rank p=0.035). Median OS in the E group and the NE group were 91.5 months and not reached (HR=2.74, log-rank p=0.02). ORR was 53% in the elderly group and 66% in the non-elderly group (p=0.32). In for OS, age was not an independent prognostic factor (HR=2.09, p=0.14) with a significant independent prognostic factor of disease status (unresectable/initially metastatic vs. recurrent (reference): HR=3.58, p=0.03). The occurrence of ≥ grade 2 non-hematologic AEs was more common in the elderly group compared to the non-elderly group (78% vs. 32%, p<0.001). Conclusions: The elderly population with advanced GIST may achieve a survival period comparable to that observed in pivotal trials with imatinib. Even with reduced doses of imatinib, careful monitoring is necessary because of the high frequency of non-hematologic ≥ grade 2 AEs in the elderly population.
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