Lyndsay Willmott, MD, presents the case of a 57-year-old woman with ovarian cancer.
Lyndsay Willmott, MD: We’d like to discuss a patient who’s presenting with classic symptoms of ovarian cancer. This is a 57-year-old woman who presented with progressive abdominal discomfort and bloating, as well as early satiety, new onset constipation, and unintentional weight loss. Her past medical history is significant for hypertension, but this has been controlled with medications. She also has a history of osteoarthritis. She comes in for her visit and physical exam reveals some right lower-quadrant tenderness. She is healthy with a performance status of 1.
To work up her symptoms, she undergoes imaging, including an ultrasound, which reveals a 4.5-cm ovarian mass. A CT scan reveals this mass, along with what appears to be lymphadenopathy and ascites. She undergoes a paracentesis for further evaluation, with cytology from that study revealing high-grade serous ovarian cancer. She then also has additional testing following this diagnosis, including germline testing, which reveals no evidence of a BRCA1 or BRCA2 mutation, and somatic testing, which is also negative for BRCA1 and BRCA2. She has subsequent testing to look for homologous recombination deficiency, and this confirms that she is showing evidence of homologous recombination deficiency.
The patient underwent up-front surgery, which included a debulking with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and resection of those involved lymph nodes. She was able to be resected to no gross residual disease. She was subsequently placed on adjuvant therapy with carboplatin and paclitaxel, which she had every 3 weeks for 6 cycles. She had normalization of her CA [cancer antigen]–125 and no evidence of disease at the completion of her treatment. Following this course of therapy, the patient and her physician had a conversation, and she was subsequently placed on bevacizumab maintenance. Following this, she was monitored. She experienced recurrence of symptoms 2 years later, which included, similar to her initial presentation, abdominal bloating and pain. She underwent imaging as well as continued CA-125 monitoring. CA-125 started to increase, and her imaging revealed recurrent retroperitoneal adenopathy. Because of her disease distribution, she was counseled about returning to chemotherapy. She was placed back onto carboplatin and paclitaxel and experienced a partial response. Following this, she was subsequently placed onto PARP inhibitor maintenance with rucaparib 600 mg twice daily. She experienced toxicity with some thrombocytopenia requiring interruption of her dose and subsequent dose reduction to 500 mg twice daily. The patient is doing well and is being monitored with a plan to continue this therapy until she experiences either additional toxicity or evidence of disease progression.
This young woman is a very classic presentation of ovarian cancer. Unfortunately, ovarian cancer has no screening modality; therefore, the majority of women who present with ovarian cancer present with these relatively innocuous symptoms and unfortunately are diagnosed in stage III or IV disease. The good news is that the majority of women are also platinum sensitive, so most women can get into remission despite presenting with advanced stage. We obviously understand that there are some prognostic factors that can help predict patients who may perform better, including certainly performance status. Other important things include BRCA status. For women who have a BRCA mutation or homologous recombination deficiency, this often means that they’re more likely to be platinum sensitive. The reason for that is related to the mechanism of action of a platinum drug. This causes DNA adducts and subsequently DNA double-stranded breaks. In women who have a BRCA mutation, they lack the ability to appropriately repair those breaks and are more likely to be more profoundly platinum sensitive. This patient did not have a BRCA mutation, but she was homologous recombination deficient, and that may also allow us to expect that she’d be more likely to have a more profound platinum-sensitive interval. And this person certainly did. This patient had 2 years from completion of her platinum-based chemotherapy before she had evidence of recurrence. These bigger platinum-free intervals are also associated with better likelihood to respond to a platinum rechallenge.
Case Overview: A 57-Year-Old Woman With Ovarian Cancer
A 57-year-old woman presented with progressive abdominal discomfort and bloating, early satiety, new-onset constipation, and unintentional weight loss
PMH: postmenopausal; hypertension—medially controlled; osteoarthritis
PE: right lower quadrant tenderness on palpation
ECOG PS 1
Pelvic exam with ultrasound showed a ~4.5-cm right ovarian mass
Chest/abdomen/pelvis CT with contrast revealed a right adnexal mass with lymph node involvement and ascites
Paracentesis (1200cc) cytology confirmed high-grade serous epithelial ovarian cancer
Germline molecular testing: BRCA1/2wt
Somatic testing: BRCA1/2 negative; HRD positive
CA-125, 360 U/mL
Diagnosis: Stage III, high-grade serous epithelial ovarian cancer
Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
Carboplatin/docetaxel q3 weeks for 6 cycles; CA-125 normalized; CR
At 2 years post chemotherapy, patient experienced abdominal bloating and pain, nausea and vomiting and progressive fatigue; CA-125 increased; imaging revealed progressive retroperitoneal adenopathy suggestive of recurrent disease; not deemed a candidate for secondary surgery
Rechallenged with carboplatin/docetaxel q3 weeks for 6 cycles; PR; predominantly enlarged lymph nodes
Rucaparib single-agent maintenance 600 mg bid
Patient developed clinically significant thrombocytopenia; dose reduced to 500 mg and patient remained on treatment until disease progression
Transcript edited for clarity.