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Case history

image A 60-year-old woman attended routine oncology follow-up 14 months after completing treatment for a stage IIIC high-grade serous ovarian carcinoma. Her previous management included optimal debulking surgery followed by six cycles of paclitaxel and carboplatin chemotherapy. A complete radiological and CA-125 response was achieved. She had no other significant medical history and specifically no cardiac history. BRCA gene testing had not been performed.

She was concerned that she was constipated and had new backache, though this was controlled with paracetamol and codeine. Her performance status was 1. Subsequent investigations revealed marker relapse (CA-125, 289 kU/l) and radiological (CT) evidence of new retroperitoneal lymphadenopathy and diffuse peritoneal thickening, consistent with relapsed ovarian carcinoma.

She discussed treatment options and the risks and benefits of further chemotherapy with her oncologist, making it clear that she wished to maintain an active lifestyle. With a platinum-free interval of more than 12 months and given that she was fit enough for combination chemotherapy, carboplatin and paclitaxel were suggested. The LCC-CARIS-01 trial, which analysed the impact of routine molecular profiling on oncologists' treatment decisions, and for which she was eligible, was also discussed. She chose to enrol in the trial and accepted the potential for a short delay (up to 3 weeks) in starting further treatment whilst multiplatform profiling of her primary tumour specimen was undertaken using the commercial Caris Molecular Intelligence (CMI; Caris Life Sciences, Irving, TX, USA) service.

The results of the profile are shown in Figure 12.1. Following its receipt, a decision was made to give six cycles of carboplatin and liposomal doxorubicin. Mid-way through this chemotherapy course, her symptoms and CA-125 improved and she was tolerating chemotherapy well, with only a low-grade palmar plantar reaction and grade 1 fatigue. She will undergo radiological imaging after six cycles. She will also be considered for the multicentre ARIEL-3 trial. This placebo-controlled randomized phase III study analyses the effect of rucaparib as maintenance therapy following platinum-based chemotherapy in patients with platinum-sensitive, high-grade serous ovarian cancer.

What was the goal of treatment?

What is the evidence base for treatment options for women with symptomatic platinum-sensitive, recurrent serous ovarian cancer?

What is the evidence base for multiplatform molecular profiling in recurrent ovarian cancer?

What is the CMI tumour profile?

How should tumour molecular profiling be used to direct treatment?

What were the key factors influencing the final treatment decision for this patient?

Figure 12.1

An example CMI tumour profile summary for a sample taken from an ovarian malignancy. Drugs of potential benefit, potential lack of benefit and indeterminate benefit are shown. These are identified via an algorithm linking specific tumour biomarkers and a literature review identifying drug targets for each of these biomarkers. Clinicians are provided both with this summary and with a comprehensive summary of biomarker results. NOS, not otherwise specified.

What was the goal of treatment?


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