AstraZeneca PLC - Lynparza EU recommendation in ovarian cancer
Lynparza recommended for approval in EU by CHMP as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer
Patients treated with Lynparza and bevacizumab lived without disease
progression for a median of 37.2 months vs. 17.7 months for bevacizumab alone
One in two women with advanced ovarian cancer has an HRD-positive tumour
AstraZeneca and MSD's Lynparza (olaparib) has been recommended for marketing authorisation in the European Union (EU) for the 1st-line maintenance treatment with bevacizumab of patients with homologous recombination deficient (HRD)-positive advanced ovarian cancer.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on a biomarker subgroup analysis of the PAOLA-1 Phase III trial, which was published in The New England Journal of Medicine.
The trial showed that Lynparza in combination with bevacizumab maintenance treatment reduced the risk of disease progression or death by 67% (based on a hazard ratio of 0.33; 95% confidence interval 0.25-0.45). The addition of Lynparza improved progression-free survival (PFS) to a median of 37.2 months versus 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.
For patients with advanced ovarian cancer, the primary aim of 1st-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission.1-3
Ovarian cancer is the fifth most common cause of cancer death in
The CHMP recommendation is for Lynparza in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of 1st-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with HRD positive status defined by either a breast cancer susceptibility gene 1/2 (BRCA1/2) mutation and/or genomic instability.
Further results from the PAOLA-1 trial recently presented during the 2020 European Society for Medical Oncology virtual congress showed that Lynparza in combination with bevacizumab maintenance treatment demonstrated a statistically significant improvement in the time to second disease progression (PFS2) versus bevacizumab alone in patients with HRD-positive advanced ovarian cancer, a key secondary endpoint. The results showed Lynparza with bevacizumab provided benefit beyond first disease progression, improving PFS2 to a median of 50.3 months versus 35.3 months with bevacizumab alone.
Lynparza in combination with bevacizumab is approved in the US and several other countries as a 1st-line maintenance treatment for patients with HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries around the world.
In 2018, there were nearly 68,000 new cases of ovarian cancer diagnosed in
Homologous recombination deficiency
HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.9
PAOLA-1 is a double-blind Phase III trial testing the efficacy and safety of Lynparza added to standard-of-care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and MSD announced in
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.
Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU,
Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 30,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology collaboration
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.
By harnessing the power of four scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in
1. Raja et al. (2012). Optimal first-line treatment in ovarian cancer. Annals on Oncology. 23 Suppl 10, x118-127.
2. NHS Choices, Ovarian Cancer Available at: https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed September 2020].
3. Ledermann et al. (2013). Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 24, pp.vi24-vi32.
4. The World Health Organization. IARC. Globocan. (2018). Available at: http://gco.iarc.fr/ [Accessed September 2020].
5. EuroHealth. (2018). Ovarian Cancer: The Silent Killer. Available at: https://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018/ [Accessed September 2020].
6. Moschetta et al. (2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of Oncology, 27(8), pp.1449-1455.
7. Bonadio et al. (2018). Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics, 73(Suppl 1): e450s.
8. Pothuri. (2013). BRCA1- and BRCA2-related mutations: therapeutic implications in ovarian cancer. Annals of Oncology, 24.
9. Moore, K. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379(26), pp.2495-2505.
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