Characteristics and predictors of outcomes with neoadjuvant imatinib in gastrointestinal stromal tumors: Real-world data from a large patient registry.
Authors: Grewal Udhayvir Singh , Loeffler Bradley T. , Evans Denisse , Call Jerry , Kaur Sahibjeet , Rothschild Sara , Milhem Mohammed M. , Monga Varun 
Published: January 2024

737 Background: The standard of care for patients with moderate or high-risk resectable gastrointestinal stromal tumors (GIST) is surgical resection followed by adjuvant therapy with imatinib. The impact of neoadjuvant imatinib on long-term outcomes is largely unknown. Methods: We interrogated the LifeRaft registry, a large international open cohort of patients with GIST. We included patients who did not have metastatic disease at diagnosis, underwent surgical resection and received neoadjuvant imatinib and had no recorded mutations of Kit exon 13 or PDGFRA exon 18 D842V. Baseline patient characteristics were described and survival probabilities were estimated and plotted using the Kaplan-Meier method. Cox regression was used to estimate the effect of demographic and clinical characteristics on recurrence-free survival (RFS) and overall survival (OS). For RFS, time was calculated from the date of surgery to disease recurrence/death, whichever came first. For OS, time was calculated from the date of surgery to death. Estimated effects of predictors were reported as hazard ratios (HR) along with 95% confidence intervals (CI). All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC). Results: Out 2,472 patients with GIST, 137 patients met the inclusion criteria and received neoadjuvant imatinib for a median of 6.8 months. Majority of the patients were aged 40 years or above (129/137, 94.2%) and were males (73/137, 53.3%). The majority of the patients had gastric GIST (72/137, 54.1%), followed by small intestine GIST (34/137, 25.6%) and other (27/137, 20.3%). Most patients had a tumor size of >10 cm (66/137, 52.4%) at the time of diagnosis followed by >5 cm - <=10 cm (42/137, 33.3%) and >2 cm - <=5 cm (18/137, 14.3%). The median RFS for the cohort was 6.1 years. On multivariable analysis, tumor size (HR 1.08, 95% CI 1.05-1.12, p<0.01) and the overall duration of treatment (neoadjuvant and adjuvant) with imatinib therapy (HR 0.98, 95% CI 0.97-0.99, p<0.01) were significantly associated with RFS. A 1-cm increase in tumor size and 1-month increase in total time on imatinib was associated with an 8% increase and 2% decrease in risk of recurrence. The median OS was 14.2 years. Female gender (HR 0.23 95% CI 0.08-0.65, p<0.01) and total length of time on imatinib (HR 0.97 95% CI 0.96-0.99, p<0.01) were found to be significantly associated with OS. Female patients were associated with a 77% decreased risk of death and a 1-month increase in the total time on imatinib was associated with a 3% decrease in the risk of death. Conclusions: We show that most patients receiving neoadjuvant imatinib have gastric GIST with tumor size >10 cm. Smaller tumor size and female gender predicted longer RFS and OS respectively. Longer total duration of imatinib therapy was associated with increased RFS and OS.