Cancer Treatment Today

A Phase II study of olaparib monotherapy for BRCA mutation–associated solid tumors, platinum-based chemotherapy was used first-line in six metastatic pancreatic cancer (MPC) patients; five (83%) achieved a partial response or complete response by RECIST criteria suggesting that BRCA-associated MPC may share the platinum sensitivity observed in other BRCA-associated malignancies.

ODD status was granted for the treatment of ovarian cancer in October 2013. Earlier this year an amended ODD status was granted to include both fallopian tube and primary peritoneal cancers following the expanded US approval of Lynparza in August 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.

Phase III POLO trial of Lynparza in pancreatic cancer was reported in July 2019. It showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as first-line maintenance therapy alone in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas in patients who haven’t responded to platinum-based chemotherapy.

The trial comparing Lynparza (olaparib) to placebo. POLO is a Phase III randomized, double-blinded, placebo-controlled, multi-center trial of Lynparza tablets (300mg twice daily) alone compared to placebo. It randomized 154 patients with gBRCAm metastatic pancreatic cancer that had not progressed on first-line platinum-based chemotherapy. Patients were randomized three to two to receive Lynparza or placebo until the disease progressed.

The primary endpoint of the trial was PFS and key secondary endpoints included overall survival (OS), time to secondary disease progression, overall response rate (ORR), disease control rate, and health-related quality of life. This drug was approved by the FDA for maintenance.
After a few early phase studiyes, a trial comparing Lynparza (olaparib) to placebo was performed. POLO was a Phase III randomized, double-blinded, placebo-controlled, multi-center trial of Lynparza tablets (300mg twice daily) alone compared to placebo.The primary endpoint of the trial was PFS and key secondary endpoints included overall survival (OS), time to secondary disease progression, overall response rate (ORR), disease control rate, and health-related quality of life. This drug was approved by the FDA, but only for maintenance.

Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets The findings from this study support the use of olaparib for BRCA-associated pancreatic cancer even in patients who have previously received multiple lines of therapy.

Golan et al (2019). Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. New England Journal of Medicine. This drug

Prescribing Information 2020

• Sarah Benafif and Marcia Hal, lAn update on PARP inhibitors for the treatment of cancer. Onco Targets Ther. 2015; 8: 519528.

  Kindler HL, et al “Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial” ASCO 2019; Abstract LBA4

  Golan T, et al “Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer” N Engl J Med 2019;