Lynparza (olaparib) Maintenance Treatment Offers Sustained Quality of Life alongside Improved Progression-Free Survival in Women with BRCA-Mutated Ovarian Cancer

CAMBRIDGE, England–(BUSINESS WIRE)– AstraZeneca today reported new data from the Phase III SOLO-2 trial of Lynparza (olaparib) 300mg twice-daily tablet maintenance treatment showing that quality of life (QoL) is sustained alongside improved progression-free survival (PFS) in women with germline BRCA-mutated (gBRCAm), platinum-sensitive, relapsed serous ovarian cancer. ¹

On three separate rating scales (functional, physical well-being and symptoms), women receiving olaparib maintenance treatment reported similar QoL to those taking placebo, according to results presented at the 2017 ASCO Annual Meeting in Chicago, US, 2-6 June 2017. ¹ Significant ‘patient-centred benefits’ of olaparib vs placebo in quality-adjusted progression-free survival (QAPFS) and time without symptoms of disease or toxicity (TWiST) were observed up to 27 months after randomisation.

Eric Pujade-Lauraine, Head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, AP-HP and Principal Investigator of SOLO-2, said: “This is very good news for patients because it suggests that olaparib not only has the potential to significantly prolong the amount of time they have before their disease progresses, but that additional time does not come at the cost of their quality of life. This may mean patients feel more able to adhere to maintenance treatment. This contrasts with what we have seen in the past with chemotherapy where the price of longer progression-free survival is often reduced quality of life leading to poor adherence to treatment.”

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The olaparib quality of life data further support the potential benefit of this first-in-class PARP inhibitor as maintenance therapy for women with BRCA-mutated relapsed serous ovarian cancer. They strengthen our confidence in targeting DNA damage response (DDR) mechanisms to selectively kill cancer cells while minimising damage to healthy tissue which may cause adverse effects that impact negatively on quality of life for patients.”

Key QoL data from SOLO-2 include: ^1,2

• Primary endpoint for patient-reported outcomes (FACT-O TOI): No appreciable detrimental effect on quality of life for patients receiving maintenance treatment with olaparib versus patients on placebo −2.90 vs -2.87 respectively, difference -0.03, 95% confidence interval [CI] –2.19, 2.13; P=0.98)
• Quality-adjusted progression-free survival (QAPFS): Mean 13.96 vs 7.28 months for olaparib and placebo respectively (difference 6.68; 95% CI 4.98, 8.54;P<0.0001)
• Time without symptoms of disease or toxicity (TWiST): Significant improvement for patients on olaparib maintenance (13.5 vs 7.21 months, difference 6.29; 95% CI 2.95, 8.58; P<0.0001)

These data build on previously reported results of SOLO-2 which met its primary endpoint of investigator-assessed PFS (HR 0.30; 95% CI 0.22 to 0.41; P<0.0001; median 19.1 months vs 5.5 months). ² PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P<0.0001). Earlier research also suggested the potential of olaparibas maintenance therapy in relapsed ovarian cancer. ³

The 300mg twice-daily tablet dose, as used in SOLO-2, potentially reduces the existing pill burden for patients from 16 capsules to four tablets per day.

The safety profile for patients treated with olaparib tablets during the trial was consistent with that observed with the currently-approved capsule formulation. ² Any adverse events (AE) Grade ≥3 were reported in 36.9% of patients treated with olaparib and in 18.2% of patients who received placebo. ² The most common non-haematological AEs reported at a frequency of ≥20% were nausea (75.9% [grade ≥3, 2.6%]), fatigue/asthenia (65.6% [grade ≥3, 4.1%]),vomiting (37.4% [≥3, 2.6%]), diarrhoea (32.8% [≥3, 1.0%]) and abdominal pain (24.1% [≥3, 2.6%). ² The incidence of serious (grade ≥3) haematological AEs were 19.5%, 5.1% and 1.0% for anaemia, neutropenia and thrombocytopenia, respectively. ⁴

– ENDS –

NOTES TO EDITORS

About SOLO-2

SOLO-2 was a Phase III, randomised, double-blind, multicentre trial designed to investigate the efficacy of olaparib tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed gBRCA-mutated ovarian cancer. ⁵ The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least two prior lines of platinum-based chemotherapy and were in complete or partial response to their most recent regimen. ^5,6 Eligible patients were randomised to receive either olaparib tablets (300mg twice daily) or placebo. ⁵

About AstraZeneca in Ovarian Cancer

Worldwide, ovarian cancer is the 7th most-commonly diagnosed cancer and the 8th most common cause of cancer death in women. ^7,8 The risk of developing ovarian cancer is increased in women with specific inherited genetic abnormalities, including BRCA mutations. ⁹ AstraZeneca is committed to the continued development of our R&D portfolio for ovarian cancer, with a focus on improved care for all patients, including the development of targeted therapies for patients with specific gene mutations such as BRCA.

About Lynparza (olaparib)

Lynparza  (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. ^10,11,12,13 It is approved by regulatory authorities in the EU and US for the treatment of women with BRCAm ovarian cancer. ^10,11 Olaparib is the foundation of AstraZeneca’s industry-leading portfolio of potential medicines targeting DNA damage response (DDR) mechanisms in cancer cells.

About ENGOT

ENGOT (European Network for Gynaecological Oncological Trial groups) is a research network of the European Society of Gynaecological Oncology (ESGO) and was founded in 2007. Currently, ENGOT consists of 19 cooperative groups from 15 European countries. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science, and enable every patient in every European country to access a clinical trial. ENGOT coordinates and promotes multinational clinical trials within Europe for patients with gynaecological cancer. This coordination is particularly relevant for academic clinical trials, translational research, research on rare diseases, and for clinical trials sponsored by the pharmaceutical industry. ¹⁴

About GINECO

GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCA (Institut National du Cancer or French NCI) for developing and conducting gynaecological and advanced breast cancer clinical trials at the national and international level. The network is nationwide, with over 500 specialised investigators belonging to more than 150 public or private oncology units. The GINECO group was founded in 1993 and is a member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). GINECO was the ENGOT leading group for the SOLO-2 trial. ⁶

About 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 at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

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.

About AstraZeneca

AstraZeneca 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 main therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.comand follow us on Twitter @AstraZeneca.

Intended audiences

This press release is issued from the AstraZeneca Corporate Headquarters in Cambridge, UK and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where AstraZeneca conducts business.

References

1. Friedlander M., et al. Relationship of health-related quality of life (HRQOL) and patient-centered outcomes with the clinical outcomes with olaparib maintenance following chemotherapy in patients with germline (g) BRCA-mutated (m) platinum-sensitive relapsed serous ovarian cancer (PSR SOC): SOLO2 phase III trial. Presented at the American Society of Clinical Oncology (ASCO), June 2 – 6, 2017. Chicago, Illinois, US

2. Pujade-Lauraine E., et al. Treatment with olaparib monotherapy in the maintenance setting significantly improves progression-free survival in patients with platinum-sensitive relapsed ovarian cancer: Results from the Phase III SOLO2 Study. Presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), March 12-15, 2017. National Harbor, Maryland, US.

3. Ledermann J., et al. Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. N Engl J Med 2012;366:1382-92.

4. AstraZeneca Q1 2017 Results – Lynparza: Ovarian cancer – Compelling efficacy and safety (P25). Available at: https://www.astrazeneca.com/investor-relations/results-and-presentations.html. Accessed May 2017.

5. National Institutes of Health. Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy. Available athttps://clinicaltrials.gov/show/NCT01874353.%20Last%20accessed%20October%202016. Accessed May 2017.

6. GINECO. Presentation of GINECO. Association ARCAGY – GINECO – Hotel Dieu Hospital. Available at http://www.arcagy.org/arcagy-organisation-et-recherche/index.php?id=56. Accessed May 2017.

7. Cancer Research UK. Ovarian cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/ovary/incidence/uk-ovarian-cancer-incidence-statistics. Accessed May 2017.

8. Cancer Research UK. Ovarian cancer mortality statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/ovary/mortality/. Accessed May 2017.

9. National Cancer Institute. BRCA1 and BRCA2: cancer risk and genetic testing. Available at https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed May 2017.

10. Lynparza (olaparib) Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, US.

11. Lynparza (olaparib) Summary of Product Characteristics. AstraZeneca Pharmaceuticals LP, Cambridge, UK.

12. O’Connor M. ‘Targeting The DNA Damage Response In Cancer’ (2015) Mol Cell. Accessed May 2017.

13. Tutt A N J., et al. Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer.  Cold Spring Harb Symp Quant Niol. 2005;70:139-48.

14. European Network of Gynaecological Oncological Trial Groups. Mission Statement and ENGOT Activities. European Society of Gynaecological Oncology 2016. Available athttps://www.esgo.org/network/engot/. Accessed May 2017.

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