AZ/Merck & Co's Lynparza scores huge ovarian cancer win

AstraZeneca and Merck & Co’s Lynparza (olaparib) has massively reduced the risk of BRCA-mutated ovarian cancer progressing in patients who have just been treated with chemo, in trial results that could change the standard of care.

Lynparza was the first drug in the poly (ADP ribose) polymerase (PARP) class to get approved in a small subset of women with ovarian cancer in 2014.

Since then AZ has joined with US-based Merck & Co to market and develop the drug and has been adding other indications to broaden its use in an increasingly competitive market for PARP drugs where Clovis, Tesaro, and Pfizer have rivals approved.

But the results announced at the European Society for Medical Oncology (ESMO) congress in Munich were perhaps the most significant from Lynparza so far, setting up a launch in an indication worth around $1 billion annually.

The 391-patient SOLO-1 phase III trial tested Lynparza tablets as a maintenance treatment for patients with newly-diagnosed, advanced BRCA-mutated ovarian cancer in complete or partial response following first line standard platinum-based chemotherapy.

Results confirmed the statistically significant and “clinically meaningful” improvement in progression-free survival for Lynparza compared with placebo.

Lynparza reduced risk of disease progression or death by 70% compared with placebo, and at 41 months of follow-up, median progression-free survival was not reached compared to 13.8 months for patients treated with placebo.

Of those receiving Lynparza, 60% remained progression-free at 36 months compared with 27% of women in the placebo arm.

The primary endpoint was progression-free survival (PFS) and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival.

The most common adverse events were nausea (77%), fatigue/asthenia (63%), vomiting (40%), anaemia (39%) and diarrhoea (34%).

The most common more serious events were anaemia (22%) and neutropenia (9%). 72% of patients on the drug remained on the recommended starting dose. Additionally, 88% of patients on the PARP drug continued treatment without an adverse event-related discontinuation.

Roy Baynes

Roy Baynes, chief medical officer, MSD Research Laboratories, said: “Our collective goal in oncology research is to improve long-term outcomes for people living with cancer. Based on the SOLO-1 trial results, Lynparza is the only PARP inhibitor to have demonstrated a significant and clinically-meaningful improvement in reducing the risk of progression for newly-diagnosed patients with advanced BRCA-mutated ovarian cancer following platinum-based chemotherapy. We are working with regulatory authorities as quickly as possible to seek approval of Lynparza for these patients.”

AstraZeneca and Merck & Co, known as MSD outside the US, are exploring additional trials in ovarian cancer, including the ongoing phase III trial, PAOLA-1.

This trial is testing the effect of Lynparza in combination with bevacizumab as a maintenance treatment for patients with newly-diagnosed advanced ovarian cancer, regardless of their BRCA status. Results are expected during the second half of 2019.

Earlier this month, the FDA granted Lynparza orphan indication in pancreatic cancer, paving the way for further trials.