What is the role of genetic testing in patients with 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 Review current recommendations regarding germline genetic testing in women with ovarian cancer, including who to test, when to test, and what tests should be performed Review recommended somatic genetic testing in women with ovarian cancer Discuss how genetic test results affect treatment planning for women with ovarian cancer Review how to navigate the conversation with patients about genetic testing and how the results may affect their prognosis and care Assess potential challenges in genetic testing, such as tissue availability, need for repeat biopsy, and likelihood of negative results

Patient History and Baseline Characteristics Age 48 years Gravidity and parity G2P2 Occupation Flight attendant Medical history Premenopausal; diabetes mellitus type 2; history of infertility Family history Prostate cancer in father; ovarian cancer in paternal aunt Baseline Characteristics Performance status Symptoms Abdominal distention, pelvic pressure, generalized abdominal pain Comorbidities Diabetes mellitus type 2 G, gravida (pregnancy); P, para (birth).

Laboratory Tests, Imaging, and Biomarkers Laboratory Testing Liver function Normal Renal function CBC findings Chemistry findings Other None performed Imaging CT Scan: C/A/P Biomarkers Testing BRCA1 Wild-type BRCA2 Germline mutation CA-125 (<35 U/mL) 1233 U/mL Other tests CEA: Normal CA-19-9: Normal CA-27.29: Normal BRCA, breast cancer susceptibility gene; CA, cancer antigen; C/A/P, chest, abdomen, pelvis; CBC, complete blood count; CEA, carcinoembryonic antigen; CT, computed tomography.

Surgical Interventions, Findings, and Diagnosis Diagnostic laparoscopy Determination of unresectable disease Peritoneal and omental biopsy Findings Frozen section: Poorly differentiated carcinoma, consistent with high-grade serous ovarian cancer Disease involving bilateral diaphragm, porta hepatis, mesenteric infiltration, extensive pelvic disease Diagnosis & Staging Stage IIIC high-grade serous carcinoma

Primary Treatment and Outcomes 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 Primary Treatment Neoadjuvant IV carboplatin and paclitaxel Interval debulking to optimal resection (TAH/BSO, omentectomy) to R0 Adjuvant IV carboplatin and paclitaxel ×3 cycles ×3 cycles BSO, bilateral salpingo-oophorectomy; CA, cancer antigen; IV, intravenous; R, residual tumor classification; TAH, total abdominal hysterectomy.

First Recurrence: Detection, Treatment, Outcomes, and Maintenance Recurrence 19 mo following completion of first-line treatment CT reveals pelvic mass and evidence of carcinomatosis Symptoms include difficulty with bowel movements, diffuse abdominal pain Examination reveals abdominal distention and a 10-cm mass on pelvic examination Recurrence Treatment IV carboplatin and paclitaxel every 3 weeks Treatment Outcomes CR by examination, CT scan, and CA-125 levels Maintenance Treatment PARP inhibition ×6 cycles CA, cancer antigen; CR, complete response; CT, computed tomography; IV, intravenous; PARP, poly ADP ribose polymerase.

Key Discussion Questions ? Key Discussion Questions When should genetic testing be performed? Should genetic testing be performed more than once during a patient’s treatment course? What are the recommended tests used for ovarian cancer treatment decisions? What challenges affect implementation of routine genetic testing and the interpretation of results? How do you talk to patients about genetic testing? What is the role of genetic counselors in the care of patients with ovarian cancer?

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-0146 09/18