1. GEMSTONE Educational Case Summary
How do you manage toxicities in patients receiving PARP inhibitors for maintenance treatment of ovarian cancer?
GEMSTONE Educational Case Summary
Last Update: June 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
Discuss available safety data for PARP inhibitors approved for maintenance treatment of ovarian cancer
Assess factors that affect benefits and risks of PARP inhibitor therapy
PARP, poly ADP ribose polymerase.

3. Patient History and Baseline Characteristics
Age
56 years
Gravidity and parity
G2P2
Occupation
Not specified
Medical history
Postmenopausal
Family history
None
Baseline Characteristics
Performance status 2
Symptoms
Fatigue, abdominal discomfort
Comorbidities
None
G, gravida (pregnancy); P, para (birth).

4. Laboratory Tests, Imaging, and Biomarkers
Laboratory Testing
Liver function
Normal
Renal function
CBC findings
Hb 8.5 g/dL
(normal range 12.0–15.5 g/dL)
Chemistry findings
None performed
Other
Imaging
CT Scan: C/A/P
Biomarkers Testing
BRCA1
Germline mutation
BRCA2
Wild-type
CA-125 (<35 U/mL)
1200 U/mL
Other tests
None performed
BRCA, breast cancer susceptibility gene; CA, cancer antigen; C/A/P, chest, abdomen, pelvis; CBC, complete blood count; CT, computed tomography; Hb, hemoglobin.

5. Surgical Interventions, Findings, and Diagnosis
TAH/BSO
Omentectomy
Tumor debulking
Findings
Ascites
Extensive intra-abdominal tumor: omentum, bilateral adnexa, uterine serosa, pelvic peritoneum, sigmoid colon serosa/mesentery, R hemi- diaphragm, caudate lobe of liver, splenic hilum
Frozen section histology: poorly differentiated carcinoma, NOS
Optimal debulking
Diagnosis & Staging
Stage IIIC high-grade serous carcinoma
BSO, bilateral salpingo-oophorectomy; NOS, not otherwise specified; R, right; TAH, total abdominal hysterectomy.

6. Primary Treatment and Outcomes
IV carboplatin and paclitaxel
Treatment Outcomes
No evidence of disease by examination, CA-125 levels, and imaging
Posttreatment
Monitor with physical examination and CA-125 levels every 3 mo ×2, then CT scan every 6 mo
Recurrence
21 mo following completion of primary chemotherapy
Diffuse intraperitoneal disease by CT of abdomen and pelvis
×6 cycles
CA, cancer antigen; CT, computed tomography; IV, intravenous.

7. First Recurrence: Treatment and Outcomes
Carboplatin and pegylated liposomal doxorubicin
Treatment Outcomes
CR by CT scan and CA-125 levels
Maintenance Treatment
PARP inhibition
Test CBC weekly for first month, then monthly
Monitor with physical examination and CA-125 levels every 3 mo
Patient develops:
Decreased Hb 8.2 g/dL (12.0–15.5 g/dL)
Elevated creatinine mg/dL (0.6–1.1 mg/dL)
Elevated ALT/AST
Recurrence
24 mo following completion of recurrence treatment chemotherapy
×6 cycles
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CA, cancer antigen; CBC, complete blood count; CR, complete response; CT, computed tomography; Hb, hemoglobin; PARP, poly ADP ribose polymerase.

8. Second Recurrence: Treatment and Outcomes
IV carboplatin and gemcitabine
Treatment Outcomes
PR by CT scan
Posttreatment
Monitor with physical examination and CA-125 levels every 3 mo ×2, then CT scan every 6 mo
Recurrence
5 mo following completion of recurrence treatment chemotherapy
×6 cycles
CA, cancer antigen; CT, computed tomography; IV, intravenous; PR, partial response.

9. Third Recurrence: Treatment and Outcomes
Weekly paclitaxel and anti-angiogenic therapy
Treatment Outcomes
PR by CT scan
Posttreatment
Monitor with physical examination and CA-125 levels every 3 mo ×2, then CT scan every 6 mo
CA, cancer antigen; CT, computed tomography; PR, partial response.

10. Key Discussion Questions?
Key Discussion Questions
What are the major safety considerations when prescribing a PARP inhibitor as maintenance treatment to a patient with ovarian cancer?
How do you determine what is a favorable risk/benefit ratio when deciding to treat with a PARP inhibitor in the maintenance setting?
PARP, poly ADP ribose polymerase.

11. 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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