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Effectiveness of Olaparib Treatment in a Patient with Gallbladder Cancer with an ATM-Inactivating Mutation
Wei Zhang1,2, Junping Shi3, Rentao Li1
1Department of Hepatobiliary Cancer and Neuro-Oncology Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
Abstract:
Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. KEY POINTS: A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. Evidence-based decisions help determine the best choice of treatment for individualized patient care.
Insights
A patient with gallbladder carcinoma (GBC) and an ATM mutation showed a 13-month response to olaparib. This case highlights targeted therapy benefits for advanced GBC, emphasizing next-generation sequencing for treatment planning.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Gallbladder carcinoma (GBC) is an aggressive malignancy with limited treatment options for advanced stages.
- Systemic chemotherapy often has suboptimal outcomes in recurrent GBC.
- Targeted therapies based on molecular profiling are emerging as a promising strategy.
Observation:
- A patient with recurrent GBC, who declined chemotherapy, was found to have ATM and STK11 mutations.
- Next-generation sequencing identified an ATM-inactivating mutation.
- Oral olaparib, a PARP inhibitor, was administered.
Findings:
- The patient experienced significant clinical symptom relief and decreased tumor markers (CA19-9) within one month.
- Radiological assessment showed a reduction in abnormal signals.
- Tumor response remained stable for approximately 13 months, indicating a durable clinical benefit.
Implications:
- This is the first report demonstrating the efficacy of olaparib in GBC with an ATM-inactivating mutation.
- The findings support the use of olaparib as a targeted therapy for select GBC patients.
- This case underscores the critical role of next-generation sequencing in identifying actionable mutations and guiding personalized treatment strategies for advanced GBC.
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