An evaluation of olaparib for the treatment of pancreatic cancer

ABSTRACT

Introduction

Advanced pancreatic cancer remains a lethal, incurable malignancy. Chemotherapy is the mainstay of systemic therapy consideration in metastatic pancreas cancer. Homologous recombinant DNA repair mutations are reported in about 7% of pancreas cancer cases and have rapidly emerged as actionable mutations.

Areas covered

A review was conducted of publications of PARP inhibitors in pancreatic malignancies with a focus on clinical trials with olaparib. This included a review of the phase II and phase III clinical trials of olaparib in pancreatic cancer.

Expert opinion

Olaparib was compared to placebo in a randomized double blind trial in cases with advanced pancreatic cancer and germline BRCA1/2 mutations, with a clinical response or stable disease after at least 16 weeks of platinum based chemotherapy. Olaparib significantly improved progression free survival, [HR = −.53, p = 0.0035] but did not improve overall survival. No differences in quality of life were noted between the two arms. Adverse events from olaparib were noted in 40% of treated patients. Objective response rate was 20% in olaparib arm and 10% in placebo treated arm. A careful consideration of the risks and benefits of this personalized therapy is advisable, prior to clinical application in germline BRCA1/2 mutated advanced pancreatic cancer.

KEYWORDS:

• PARP
• BRCA1/2
• homologous repair
• pancreas cancer

Article highlights

• Olaparib is FDA approved as maintenance therapy in adult patients with advanced pancreas adenocarcinoma whose disease had not progressed for at least 16 weeks of a platinum based first-line chemotherapy regimen and having deleterious or suspected deleterious germline BRCA-mutations.

• NCCN guidelines recommend germline BRCA testing for all patients with advanced pancreas cancer regardless of family history

• Olaparib maintenance improved progression free survival post chemotherapy

• Durable remissions and prolonged benefit were noted in small proportion of patients

• Monitoring for adverse events such as cytopenias and gastrointestinal toxicities is advised

• Quality of life was no different with olaparib therapy as compared to placebo.

• Careful discussion of benefits and risks is advised during consideration of olaparic therapy in BRCA mutation pancreas cancer.

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.