AstraZeneca's Lynparza has outperformed chemotherapy in a phase III trial involving patients with metastatic breast cancer, setting up possible regulatory filings in the second half of this year.
Lynparza (olaparib) is the first drug in the PARP inhibitor class to show activity beyond ovarian cancer in a randomised trial, according to AZ, which said it will be "working with regulatory authorities to make Lynparza available to patients with this type of breast cancer".
Compared to standard chemotherapy with capecitabine, vinorelbine or eribulin, Lynparza achieved a "statistically-significant and clinically-meaningful" improvement in progression-free survival (PFS) in the OLYMPIAD trial, said the company, although details will not be available until the data is presented at a forthcoming medical meeting.
The open-label OLYMPIAD study enrolled patients with HER2-negative metastatic breast cancer whose tumours expressed BRCA1 or BRCA2 mutations. Patients were treated with olaparib at a dose of 300mg twice-daily or period cycles of chemotherapy given by injection.
It comes after a phase II trial of olaparib in advanced breast cancer, which provided positive proof of concept of the efficacy and tolerability of targeted therapy with olaparib in BRCA-positive tumours. If approved, it could dramatically expand the market for Lynparza, which brought in $218m in sales last year from its current indication in ovarian cancer.
Researchers studying BRCA-positive breast cancer have been eagerly awaiting the results of trials of PARP inhibitors in these patients, as they currently have to rely on chemotherapeutic agents and there is still no consensus on the best regimen to use.
Approval of the new class would give these patients the first targeted treatment option, and raise the possibility of combining drugs like olaparib with chemotherapy to boost efficacy.
Lynparza was the first PARP inhibitor to be approved in 2014 and was on its own in the class until Clovis Oncology picked up an FDA approval for its Rubraca (rucaparib) rival last December. A third PARP inhibitor - Tesaro's niraparib - is under regulatory review for ovarian, fallopian tube and peritoneal cancer.
"These results are positive news for patients with BRCA-mutated metastatic breast cancer, a disease with a high unmet need," said AZ's chief medical officer Sean Bohen. "This is highly encouraging for the development of our broad portfolio which aims to treat multiple cancers by targeting DNA damage response pathways."
AZ has previously said it will roll out six new targeted cancer therapies between 2014 and 2020, with Lynparza and third-generation EGFR inhibitor Tagrisso (osimertinib) for lung cancer the first two launched.
Credit Suisse forecasts predict Lynparza sales will reach $1.6bn in 2020, just ahead of Rubraca, with niraparib in third place with just over $1bn in sales in that year.