ASCO: AstraZeneca, Merck to expand Lynparza's blockbuster territory with big early breast cancer showing

Thanks to regular screening, many breast cancer cases are caught early. And in some patients at high risk of tumors coming back, treatments are deployed around surgery to increase the chance of a cure.

Now buoyed by a new clinical trial success, AstraZeneca and Merck are eyeing a HER2-negative niche in the post-surgery breast cancer market to further expand their blockbuster PARP inhibitor Lynparza.

Using Lynparza after surgery in high-risk, HER2-negative early breast cancer reduced the risk of disease recurrence or death by 42% over placebo, according to data presented during the plenary session at the virtual American Society of Clinical Oncology meeting.

The results, from the phase 3 OlympiA trial, were for patients whose tumors bear BRCA 1/2 mutations, which make up about 5% of all breast cancer cases in the U.S. and predispose women to aggressive disease.

At three years, about 85.9% of Lynparza patients were still alive without invasive breast cancer, compared with 77.1% in the placebo group.

RELATED: AstraZeneca's already dominant Lynparza lines up for early breast cancer with new trial win

Lynparza is now the first PARP inhibitor to claim a win that, as ASCO put it, “may change the standard of care in adjuvant systemic therapy” for germline BRCA1/2-mutated, HER2-negative early breast cancer. And it’s a home run.

Two breast cancer experts SVB Leerink talked to ahead of the data revelation said a 30% reduction in the so-called invasive disease-free survival marker would be clinically meaningful enough to drive physician uptake of Lynparza in early breast cancer patients. Lynparza’s 42% showing easily cleared that threshold.

Previously, Eli Lilly’s CDK4/6 inhibitor Verzenio reported a 25.3% reduction in the risk of cancer recurrence when used as an adjuvant therapy for high-risk HR-positive, HER2-negative early breast cancer. And that was also seen as a practice-changing improvement.

RELATED: ESMO: Lilly's Verzenio pressures Pfizer with practice-changing win in early breast cancer

In the OlympiA trial, Lynparza was actually given after current standard-of-care chemotherapy that’s used pre- or post-surgery. The regimen was designed that way—rather than trying to replace chemotherapy with Lynparza—because AZ and Merck are trying to “give the best possible therapy to drive toward a cure,” AZ’s oncology business chief, Dave Fredrickson, explained in an interview.

Lynparza also showed it could reduce the risk of distant tumor recurrence or death by 43%.

The key information on whether Lynparza can help patients live longer was not mature at the interim analysis with 2.5 years of median follow-up, but the survival curve was trending in Lynparza’s favor with a 32% reduction in the risk of death. The study remains ongoing to read out the overall survival data.

Before the early breast cancer win, Lynparza was the first PARP inhibitor allowed to treat BRCA-mutated metastatic breast cancer thanks to an FDA go-ahead in 2018.

Fredrickson described the latest Lynparza trial as part of AstraZeneca’s “explicit strategy” to go early in the treatment line for its cancer drugs across different tumor types.

The company’s top-selling Tagrisso recently entered early-stage EGFR-mutated non-small cell lung cancer after showing its use after surgery could cut the risk of disease recurrence or death by a whopping 83% over placebo in patients with stage II and IIIA disease. And several studies are testing its PD-L1 inhibitor Imfinzi as a pre- or post-surgery treatment for different cancers.

RELATED: AstraZeneca's Tagrisso, Imfinzi have been slowed by COVID-19, but growth is coming: exec

AZ’s currently trying to sharpen Lynparza's edge amid increasing competition from GlaxoSmithKline’s rival PARP inhibitor Zejula, and OlympiA once again put it one step ahead.

Despite a unique approval that covers HRD-negative ovarian cancer in the so-called first-line maintenance setting, Zejula was still nowhere near Lynparza in terms of sales. In the first quarter, Zejula hauled in sales of £88 million ($124 million), while Lynparza reeled in $543 million for AZ’s share.

The next major milestone for Lynparza will be data from the PROpel trial later this year, which could move the drug up one line in the treatment sequence to newly diagnosed castration-resistant prostate cancer.