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.

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.

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.

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.

Treatment at First Recurrence: Chemotherapy, Surgery, and Maintenance Treatment Options IV carboplatin and gemcitabine Tolerance limited by chronic SBO requiring surgical exploration Declining CA-125 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.

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?

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-0126 04/18