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.

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.

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).

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.

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.

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.

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 1.86 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.

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.

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.

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.

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. TESARO, Inc. | 1000 Winter Street, Suite 3300 | Waltham, MA 02451 ©2018 TESARO, Inc. All rights reserved. PP-DS-US-0144 08/18