Metastatic NSCLC with ATM mutations: 28-month response to olaparib before progression

What happened, in summary

This 91-year-old man, a former smoker with complex medical history, was first diagnosed in September 2014 after liver metastases were found. Liver biopsy showed poorly differentiated carcinoma positive for CK7 and CEA and negative for CK20, Napsin A, synaptophysin, PSA, PAX8, and TTF-1. PET-CT scans, EGD, colonoscopy, and tumor-marker testing did not identify a clear primary site, but lung cancer was considered the most plausible source. He began weekly dose-reduced paclitaxel plus carboplatin, with radiation directed to the liver lesion. A later restaging scan found a new left pubic bone lesion, and biopsy again showed adenocarcinoma. Subsequent treatment included gemcitabine plus nab-paclitaxel, nivolumab, and irinotecan. His liver lesions stayed stable from 2016 to 2019 on irinotecan, but pulmonary nodules gradually appeared and increased. By October 2021, PET-CT showed pleural effusion and increasing mildly hypermetabolic pulmonary nodules. Circulating tumor DNA found ATM R3008C and ATM L427S mutations, with additional FGFR3 and CHEK2 findings; common lung cancer drivers such as EGFR, ALK, KRAS, and BRAF were negative. Because options were limited and he wanted more cancer-directed treatment, olaparib was started in February 2022 and increased to 100 mg twice daily, with anemia limiting further escalation. Scans at 7, 18, and 22 months showed sustained remission and near-complete radiologic response. As of June 2024, PET-CT showed new progression in a left lower-lobe lung nodule after 28 months of benefit, though olaparib was still being continued in October 2024 with repeat imaging planned. His quality of life had improved during the response period, especially because he was free from repeated pleural fluid drainage.