(P 47) PATIENT SURVIVAL IN METASTATIC GIST WITH IMATINIB-SENSITIVE MUTATIONS: REAL WORLD DATA FROM GERMAN REFERRAL CENTER (2008-2021)

Objective: The outcome of patients with metastatic GIST and imatinib-sensitive primary mutations has dramatically improved. However, published follow-up data from clinical trials commonly excludes elderly and multimorbid patients. In addition, accessibility to drugs may vary between different health care systems. Data to advise patients about outcome at various treatment-lines is scarce. Hence we aimed to analyze the outcome of patients from a large German GIST referral center from the recent 15 years.

Methods: The institutional GIST database (n=773) was queried for patients who were diagnosed with metastatic disease after 2008 att which time at least three lines of treatment were available in Germany. We filtered for patients that harbored imatinib-sensitive mutations as defined by KIT Exon 9 or 11 mutations. In patients with unknown mutational status, response to imatinib treatment for >1 year was defined as Imatinib-sensitive. In total, 163 patients were identified and analyzed for treatment-line specific progression-free survival and overall survival.

Results: The cohort consisted of 70 female and 93 male patients. Median age at diagnosis of metastases was 59 years and median follow-up was 50months. 127 had a primary exon 11 and 36 a primary exon 9 mutation. 58 patients had died of their disease at the time of analysis. The total patient cohort had a median overall survival (OS) of 84, 44 and 22 months (N= 156, 89 and 82, respectively) after start of palliative imatinib treatment, imatinib failure and sunitinib failure, respectively. Median overall survival was 97 months for patients with primary exon 11 mutation and 89 months in those with a primary exon 9 mutation (p=0,316) (figure B). Notably, the interval between diagnosis of primary tumor and metastatic disease (synchronous vs metachronous diagnosis) did not impact survival. In addition, progression-free survival was identical for imatinib in patients who had received imatinib perioperatively.

Conclusion: In this retrospective cohort we provide real-world data on the outcome of patients in an era of access to multiple kinase inhibitors. The median overall survival by far exceeds historical data for patients with primary exon 11 and exon 9 mutations (8.1 and 7.4 years vs 3.7 years in the meta-GIST analysis for EU patients) which may hint at the survival impact of additional treatment lines since 2008. Notably, adjuvant treatment did not impact time-to-progression and overall survival of patients receiving imatinib for metastatic disease underscoring that apoptotic resistance rather than secondary KIT-mutations are responsible for relapse of patients (figure A).