The Highs and Lows of Neoadjuvant Treatment, Debulking Surgery, and Pamiparib Therapy

A 56-year-old woman presented in September 2013 with two months of abdominal distension and two weeks of abdominal pain. Workup revealed a large cystic-solid mass (128×101×114 mm³), extensive ascites, enlarged lymph nodes, and a CA-125 level of 4,138.1 U/mL. Cytology from her ascitic fluid and biopsy confirmed high-grade serous ovarian adenocarcinoma. Due to the size and extent of her disease, a multidisciplinary team recommended neoadjuvant chemotherapy rather than immediate debulking.

She received three cycles of carboplatin (AUC 5) and paclitaxel (175 mg/m²) in three-week intervals. With tumor shrinkage achieved, she proceeded to interval debulking surgery, which successfully removed all visible disease. Post-surgery, she completed five more cycles of the same chemotherapy regimen. Her CA-125 levels normalized (5.9 U/mL), marking a complete response initially.

Despite 32 months of follow-up, the cancer recurred in 2017 with increased CA-125 (43.1 U/mL) and CT evidence of pelvic carcinomatosis. She refused secondary surgery and opted for an additional six cycles of carboplatin-paclitaxel. Although a partial response was achieved (CA-125: 7.8 U/mL), she again experienced relapse 16 months later in November 2018. Genetic testing revealed a pathogenic BRCA2 mutation, prompting her to enroll in a clinical trial for pamiparib, a PARP inhibitor, at 60 mg twice daily.

Within months, imaging showed encouraging shrinkage of metastatic nodules, but she experienced repeated cycles of grade III neutropenia and anemia. After 20 months on pamiparib, she developed therapy-related acute myeloid leukemia (t-AML), confirmed by bone marrow biopsy and flow cytometry. Although supportive care was provided, including blood transfusions and granulocyte colony-stimulating factor (G-CSF), her hematologic condition deteriorated. She succumbed to hematemesis at home two months later.

Her case highlights the complex balance between controlling advanced ovarian cancer with repeated chemo and targeted agents, and the potential for grave secondary complications such as t-AML—underscoring the importance of vigilant monitoring.