Metastatic gastric cancer with an ATM mutation responding to olaparib

What happened, in summary

A 66-year-old man with a strong family history of gastric cancer developed worsening upper-abdominal pain and reflux in February 2022. Endoscopy found an ulcerated bleeding mass in the stomach, and biopsy showed adenocarcinoma with signet-ring features. CT imaging showed peritoneal carcinomatosis, establishing Stage IV disease. Testing found HER2-negative, MMR-proficient disease with PD-L1 of 15%, and germline testing identified a pathogenic ATM mutation.

He started fluorouracil, leucovorin, oxaliplatin and docetaxel in February 2022, with nivolumab added the following month. The cancer responded strongly. Olaparib, a PARP inhibitor, was added in July because of the ATM mutation. Oxaliplatin was later stopped because the intensive regimen was difficult to tolerate. In November 2022, severe immune-related pneumonitis required hospitalization and oxygen, so chemotherapy and nivolumab were discontinued. He then continued olaparib alone.

The response remained durable through most of 2023. Endoscopies in June and October showed normal-appearing stomach lining and biopsies negative for malignancy. In December 2023, however, imaging again showed multiple peritoneal nodules consistent with carcinomatosis. Right pleural thickening was suspicious but not confirmed as cancer spread. By the latest follow-up, the disease had progressed after a prolonged response of about 18 months.