There was good news at the ESMO conference for both AstraZeneca and Clovis Oncology as they push to extend the use of their PARP inhibitors into new cancer patient groups.
For AZ, the results of the SOLO-1 trial of Lynparza (olaparib) as a first-line treatment for early-stage BRCA-positive ovarian cancer met already high expectations, with patients given the drug as a maintenance therapy looking at three additional years of progression-free survival compared to placebo.
That’s an extrapolation as the PFS data isn’t mature yet, but is nevertheless a practice-changing result, according to oncologists at ESMO. All told, 60% of patients receiving Lynparza remained progression-free at three years compared to 27% of the placebo group, and Lynparza is the only PARP inhibitor to have positive data as a first-line maintenance therapy in these patients.
“While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression free at four years as compared to only 11% for placebo speaks to this hope,” said SOLO-1 co-principal investigator Kathleen Moore of the University of Oklahoma whilst presenting the results at ESMO.
“This study demonstrates an outstanding improvement in PFS over placebo which is maintained even after the olaparib is stopped at two years,” she added.
AZ and its Lynparza marketing partner Merck & Co/MSD, say they are now “working with regulatory authorities as quickly as possible to seek approval of Lynparza for these patients”, helping Lynparza extend its lead over its PARP inhibitor rivals, Tesaro’s Zejula (niraparib) and Clovis’ Rubraca (rucaparib).
All three drugs are already approved for maintenance in relapsed/refractory ovarian cancer, but first-line approval would allow Lynparza to move up the treatment pathway ahead of its competitors.
Tesaro is expecting phase 3 results in the same setting for Zejula next year. Meanwhile, third-to-market Clovis has taken a slightly different tack, focusing its first-line maintenance efforts on a combination study of Rubraca with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) in ‘all-comer’ first-line ovarian cancer, attempting to extend the use of its PARP inhibitor beyond BRCA-positive patients. AZ and MSD are also trialling Lynparza alongside Roche’s Avastin (bevacizumab) in this broader patient group.
Prostate cancer win
Clovis had its own clinical win to talk about at ESMO, revealing data from the TRITON2 trial of Rubraca as a monotherapy in men with BRCA1/2 mutated metastatic castration-resistant prostate cancer, who have received at least one prior androgen receptor therapy and taxane-based chemotherapy.
Preliminary data from the trial revealed a 44% response rate among the 25 evaluable men with a BRCA1 or 2 mutation, the first time that a PARP drug has shown a benefit in this indication. Rubraca picked up a breakthrough designation from the FDA in prostate cancer earlier this year, and has said it hopes to be in a position to file for approval in the latter half of 2019.
If that pans out, Clovis would be able to be the front-runner in a market for its PARP inhibitor estimated to be worth upwards of $500m a year according to some analysts – rather than playing catch-up in ovarian and breast cancer.