- A subgroup of ovarian cancer patients given Lynparza as a first-line maintenance therapy lived significantly longer without their disease progressing than those receiving placebo, according to fresh clinical results that an analyst described as a "home run" for the drug's developer, AstraZeneca.
- Data from the Phase 3 SOLO-1 trial, presented Sunday at the European Society of Medical Oncology's annual conference, found that, compared to placebo, using Lynparza after first-line platinum-based chemotherapy reduced the risk of disease progression or death by 70% for ovarian cancer patients with BRCA mutations. About 15% of ovarian cancer diagnoses are related to such mutations.
- While most adverse events seen in the trial were mild or moderate in nature, 21% of the patients on Lynparza experienced serious side effects versus 12% of the placebo group. The most common Grade 3 or higher adverse effects were anemia and low levels of a type of white blood cell called a neutrophil. New primary cancers developed in 2% of both the Lynparza and placebo arms.
AstraZeneca has a lot riding on Lynparza (olaparib). Following a major clinical setback with its PD-L1 inhibitor Imfinzi (durvalumab), the British pharma and Merck & Co. teamed up in a deal worth potentially $8.5 billion centered on testing combinations of Lynparza and immuno-oncology drugs.
While not focused on combos, SOLO-1 underscores how Lynparza's label could further expand. The drug holds indications for maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers who are in a complete or partial response to platinum-based chemotherapy, as well as adult BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
In a statement announcing the new data, Roy Baynes, chief medical officer at Merck Research Laboratories, said his company is working "as quickly as possible" with regulators to get Lynparza approved as first-line maintenance therapy.
Merck's enthusiasm is understandable, given how positive the SOLO-1 results were. According to investment bank Leerink, a recent MEDACorp survey found oncologists would view a hazard ratio between 0.5 and 0.7 as "practice changing." Results showed the hazard ratio registered even lower, at 0.3.
"The findings promise to change practice in this subgroup of patients with a BRCA mutation," said Isabelle Ray-Coquard, a professor of medical oncology at France's Université Claude Bernard Lyon, in an Oct. 21 statement from ESMO.
The survey responses also indicated that the oncologists expected penetration of PARP inhibitors in the second-line maintenance therapy setting for ovarian cancer will increase from 45% to 55% in the next year. And about 60% of respondents indicated they would use PARP inhibitors in the frontline maintenance setting in BRCA-positive patients.
That news is also positive for rival PARP inhibitors like Clovis Oncology's Rubraca (rucaparib) and Tesaro's Zejula (niraparib) — therapies that could provide some competitive pressure to AstraZeneca and Merck.
But Lynparza's lead may be hard for investors to overlook.
"While we view these data as potentially expanding the market for both Tesaro and Clovis," Leerink analyst Andrew Berens wrote in an Oct. 21 note, "we think investor sentiment will be mixed, given concerns that AstraZeneca/Merck will dominate the market, and frontline usage will cannibalize downstream opportunities."
Ray-Coquard noted that two overarching questions remain following the SOLO-1 readout. The first is whether the benefit seen with Lynparza in BRCA-positive patients extend to everyone with high-grade serous carcinomas.
"Looking at existing results in relapse with PARP inhibitor maintenance in all comers, we can anticipate excellent results for all patients with high grade serous or endometrioid ovarian carcinoma," she said.
The second revolves around identifying the best type of maintenance therapy for ovarian cancer patients.
"Standard first line therapy in many countries is chemotherapy plus bevacizumab maintenance for the majority of advanced disease, but the question remains whether maintenance with olaparib alone, or in combination with bevacizumab is preferable."
AstraZeneca's stock was relatively unmoved in late Monday morning trading, while Tesaro's and Clovis' were down more than 5% and 18% respectively.