Lynparza added to bevacizumab reduced the risk of disease progression or death by 41% in the overall PAOLA-1 trial population in advanced ovarian cancer.- AstraZeneca + Merck Inc.

AstraZeneca and MSD Inc., announced detailed positive results from the Phase III PAOLA-1 trial, showing Lynparza (olaparib) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in women with newly-diagnosed advanced ovarian cancer. The trial compared Lynparza when added to standard-of-care (SoC) bevacizumab vs. bevacizumab alone in women in the 1st-line maintenance setting, irrespective of their genetic biomarker status or outcome from previous surgery.

Investigator-assessed results showed Lynparza added to bevacizumab reduced the risk of disease progression or death by 41% (equal to a hazard ratio of 0.59) and improved PFS to a median of 22.1 months vs. 16.6 months for those treated with bevacizumab alone. At two years since trial initiation, 46% of women treated with Lynparza added to bevacizumab showed no disease progression vs. 28% of women receiving bevacizumab alone.

The sensitivity analysis of blinded independent central review (BICR) of PFS was consistent, showing a similar improvement with a median of 26.1 months for Lynparza added to bevacizumab vs. 18.3 months for bevacizumab alone. The safety and tolerability profile of Lynparza and bevacizumab were consistent with those known from previous trials for each medicine, and with no detriment to quality of life.The results were presented during the Presidential Symposium of the 2019 European Society of Medical Oncology (ESMO) congress in Barcelona, Spain (Abstract #LBA2_PR)

The trial also included exploratory sub-group analyses including BRCA-mutated (BRCAm) and broader homologous recombination deficiency (HRD) populations, which showed treatment with Lynparza added to bevacizumab demonstrated greater benefit vs. bevacizumab alone. In the BRCAm-positive sub-group, Lynparza added to bevacizumab reduced the risk of disease progression or death by 69% (equal to a hazard ratio of 0.31). In the broader HRD-positive sub-group, which represents approximately half of women with newly-diagnosed advanced ovarian cancer and includes BRCAm, Lynparza added to bevacizumab reduced the risk of disease progression or death by 67% (equal to a hazard ratio of 0.33).

Jos� Baselga, Executive Vice President, Oncology R&D, said: �This trial was designed to reflect everyday clinical practice using a global standard-of-care treatment with Lynparza. The results showed at two years nearly half of women with advanced ovarian cancer were progression-free with Lynparza added to bevacizumab as a 1st-line maintenance treatment, regardless of their biomarker status or surgical outcome. We are working with regulatory authorities to bring Lynparza to these patients as quickly as possible.�

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre L�on B�rard and President of the GINECO group, said: �The goal of 1st-line, including maintenance, treatment for women with newly-diagnosed advanced ovarian cancer is to delay relapse. Unfortunately, the risk of relapsing is high, as two out of three women relapse within three years of initial diagnosis. In PAOLA-1, the results of Lynparza added to bevacizumab were significant and have the potential to change clinical practice in how women with advanced ovarian cancer are treated in the 1st-line maintenance setting.�

Overall Grade 3 or above adverse events (AEs) were 57% for Lynparza added to bevacizumab and 51% for bevacizumab alone. The most common AEs greater than 20% were nausea (53%), fatigue (53%), hypertension (46%), anaemia (41%), lymphopenia (24%), vomiting (22%) and arthralgia (22%). Grade 3 or above AEs were hypertension (19%), anaemia (17%), lymphopenia (7%), neutropenia (6%), fatigue (5%), nausea (2%), diarrhoea (2%), leukopenia (2%) vomiting (1%) and abdominal pain (1%). AEs led to dose interruption in 54% of patients on Lynparza while 20% of patients discontinued treatment.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for the treatment of advanced ovarian cancer and metastatic breast cancer and has been used to treat over 25,000 patients worldwide. It is the only PARP inhibitor with positive Phase III trials in four different cancer types (ovarian, breast, pancreatic and prostate).