1. GEMSTONE Educational Case Summary
How do you select a maintenance strategy for a patient with BRCAwt platinum-sensitive recurrent ovarian cancer?
GEMSTONE Educational Case Summary
Last Update: March 23, 2018
GEMSTONE, a committee of ovarian cancer experts, provided direction and approval of the hypothetical patient scenario presented in this educational resource. TESARO, Inc. provided writing and organizational support to GEMSTONE in the generation of this material.

2. Case Objectives
Consider factors affecting maintenance therapy decisions after second-line chemotherapy
Discuss how BRCAwt status affects treatment choice and prognosis
Navigate among currently available options for maintenance therapy
BRCA, breast cancer susceptibility gene; wt, wild-type.

3. Patient History and Baseline Characteristics
Age
44 years
Gravidity and parity
G4P4
Occupation
Human relations specialist
Medical history
Crohn’s disease, mild
Stage IIIC ovarian cancer s/p primary cytoreductive surgery to R0 in 2015, followed by IV/IP chemotherapy ×6 cycles
Diagnosed 12 mo after last IP chemotherapy cycle with first recurrence
Family history
Breast cancer
Baseline Characteristics
Performance status
Symptoms
Mild bloating, early satiety
Comorbidities
None
G, gravida (pregnancy); IP, intraperitoneal; IV, intravenous; P, para (birth); R, residual tumor classification; s/p, status post.

4. First Recurrence: Laboratory Tests, Imaging, and Biomarkers
Laboratory Testing
Liver function
Normal
Renal function
CBC findings
Chemistry findings
Albumin 3.0 g/dL
BMI (<25) 22
Imaging
CT Scan: C/A/P
Biomarkers Testing
BRCA1
Wild-type
BRCA2
CA-125 (<35 U/mL)
25 U/mL
TP53
Mutant
DNA MMR pathway
Intact (MSS)
TMB
Intermediate
BMI, body mass index; BRCA, breast cancer susceptibility gene; CA, cancer antigen; C/A/P, chest, abdomen, pelvis; CBC, complete blood count; CT, computed tomography; MMR, mismatch repair; MSS, microsatellite stable; TMB, tumor mutational burden.

5. Treatment at First Recurrence: Chemotherapy, Surgery, and Maintenance Treatment Options
IV carboplatin and gemcitabine
Tolerance limited by chronic SBO requiring surgical exploration
Declining CA and regression of carcinomatosis on CT supported at least PR to chemotherapy
Surgical Interventions & Findings
Exploratory laparotomy for chronic SBO
Prior to surgery it was unclear if patient was experiencing disease progression
Lysis of adhesions, secondary cytoreduction of “rind” in the pelvis with partial small bowel resection performed
Treatment Outcomes & Findings
PR to 3 cycles carboplatin and gemcitabine
“Adhesioma” in pelvis, trapping small bowel
Fibrotic adhesions infiltrated with microscopic tumor
Persistent ascites and SBO during presurgery chemotherapy due to adhesions and not disease progression
Chemotherapy
IV carboplatin and gemcitabine
Attempted to complete an additional 3 cycles, but patient developed severe carboplatin allergy and grade 3 thrombocytopenia
Overall response to 2L treatment: CR
Risk for recurrence considered high; surgery was required to achieve CR and patient unable to complete 2L regimen
×2 cycles
Maintenance Treatment
Maintenance strategies discussed
Anti-angiogenic therapy recommended, but patient declined due to history of bowel resection and concern for bowel perforation
PARP inhibitors discussed and patient accepted
×3 cycles
2L, second-line; CA, cancer antigen; CR, complete response; CT, computed tomography; IV, intravenous; PARP, poly ADP ribose polymerase; PR, partial response; SBO, small bowel obstruction.

6. Key Discussion Questions?
Key Discussion Questions
What patient factors affect eligibility for maintenance therapy?
How do you determine what is a favorable risk/benefit ratio in the maintenance setting? How can this be optimized?
Which patient factors guide decisions about maintenance strategies?
What disease factors guide decisions about maintenance strategies?

7. GEMSTONE
GEMSTONE, a committee of ovarian cancer experts, provided direction and approval of the material in this educational resource. TESARO, Inc. provided writing and organizational support to GEMSTONE in the generation of this material.
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