Rapid and durable response to fifth-line lorlatinib plus olaparib in an ALK-rearranged, BRCA2-mutated metastatic lung adenocarcinoma patient with critical tracheal stenosis: a case report

Treatment options for heavily treated anaplastic lymphona kinase (ALK)-positive nonsmall cell lung cancer (NSCLC) patients, who typically bear-resistant mechanisms to ALK tyrosine kinase inhibitors (TKIs), are usually limited to chemotherapy, which elicits limited clinical benefit and may incur severe toxicity. It is clinically relevant to explore other revenues for these patients. poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib are currently approved to treat BReast CAncer gene 1/2 (BRCA1/2)-mutated patients in a few tumor types. There have been a trial and two case reports of an olaparib-containing regimen in treating epidermal growth factor receptor (EGFR)-positive or driver-negative NSCLC. We report a case of a 27-year-old female nonsmoker diagnosed with ALK-rearranged metastatic lung adenocarcinoma. She was treated with alectinib and acquired ALK p.I1171N and p.V1180L mutations. Germline BRCA2 p.F2801fs was also identified. After sequential lines of ceritinib and chemotherapy, lorlatinib was chosen as the fourth-line therapy and maintained control for 6 months. Shortly after progression, the patient was admitted to the ICU due to critically severe stenosis caused by a tracheal mass and soon relieved by embolization and stenting. Afterward lorlatinib plus olaparib was started and elicited a rapid response within 1 month. The progression-free survival was 6 months as of the latest follow-up, with the best response of partial response. To the best of our knowledge, this case is the first to provide clinical evidence of antitumor activity of olaparib plus ALK TKI in ALK-positive, gBRCA-mutated metastatic NSCLC. Together with previous reports in EGFR-positive or driver-negative patients, our finding warrants further studies on PARP inhibition in BRCA1/2-mutated NSCLC.