AstraZeneca/MSD’s Lynparza in Combination with Roche’s Avastin Recommended in England for HRD-Positive Advanced Ovarian Cancer

Compiled by Keke

Recently, foreign media reported that the UK’s National Institute for Health and Care Excellence (NICE) has recommended, through the Cancer Drugs Fund (CDF), the use of AstraZeneca/Merck Sharp & Dohme’s Lynparza (olaparib) in combination with Roche’s Avastin (bevacizumab) as maintenance therapy for patients with homologous recombination deficiency (HRD)-positive advanced ovarian, fallopian tube, and primary peritoneal cancer who have had a complete or partial response to first-line platinum-based chemotherapy and bevacizumab.

This recommendation is based on data from the Phase III PAOLA-1 clinical trial, which demonstrated that olaparib combined with bevacizumab reduced the risk of disease progression or death by 67% compared to bevacizumab monotherapy. The combination of olaparib and bevacizumab also extended patients’ progression-free survival (PFS) from 17.7 months to 37.2 months.

In this study, approximately 48% of patients were newly diagnosed with HRD-positive advanced ovarian cancer.

The UK National Health Service (NHS) supports the introduction of olaparib in combination with bevacizumab therapy, and is providing genomic HRD testing for patients receiving this treatment for the first time. This test analyzes a single tumor sample to determine HRD status and somatic BRCA mutation status.

Olabarib (olaparib), as an inhibitor of poly(ADP-ribose) polymerase (PARP), is known as a PARP inhibitor. BRCA1/2 mutations may genetically predispose individuals to certain cancers and may also confer resistance to other cancer therapies. However, these cancers sometimes exhibit a unique vulnerability, as cancer cells become increasingly reliant on PARP for DNA repair, enabling them to continue dividing. This implies that if cancers are susceptible to this therapeutic approach, drugs that selectively inhibit PARP may be beneficial.

In December 2014, the European Medicines Agency (EMA) of the European Union and the U.S. Food and Drug Administration (FDA) approved olaparib as a monotherapy. The U.S. FDA approved the drug for the treatment of advanced ovarian cancer with germline BRCA mutations (gBRCAm) in patients who had received three or more prior lines of chemotherapy. In January 2018, olaparib became the first PARP inhibitor approved by the U.S. FDA for the treatment of gBRCAm metastatic breast cancer. The drug was developed and initially administered to patients by the UK biotechnology company KuDOS Pharmaceuticals. Since AstraZeneca acquired KuDOS in 2006, AstraZeneca and Merck & Co., Inc. (MSD) have jointly conducted clinical development of the drug. Olaparib in combination with temozolomide has demonstrated significant clinical activity in recurrent small cell lung cancer.

Reference Sources:

1. Wikipedia

2.NICE approves Lynparza plus Avastin via Cancer Drugs Fund