Lynparza/Imfinzi Regimen Is ‘Encouraging’ for Advanced Ovarian Cancer

A regimen containing Lynparza, Imfinzi, Avastin and chemotherapy is showing promise for a certain group of patients with advanced ovarian cancer.

The addition of Lynparza (olaparib) and Imfinzi (durvalumab) to Avastin (bevacizumab) and chemotherapy tended to improve outcomes compared to Avastin and chemotherapy without the two other agents in patients with previously untreated advanced high-grade epithelial ovarian cancer without BRCA mutations, according to an interim analysis from the phase 3 DUO-O clinical trial.

In particular, the drug combination statistically improved average progression-free survival, which is the time patients live during and after treatment without their disease spreading or getting worse.

Researchers also plan to analyze overall survival (time from treatment until death of any cause) and other endpoints such as second progression, health-related quality of life, pathological complete response, percentage of patients whose disease shrinks or disappears from treatment and others, though those data are not yet mature, according to a press release from AstraZeneca, the pharmaceutical company manufacturing Lynparza and Imfinzi.

"While there has been significant progress for patients with advanced ovarian cancer, an unmet need still remains. These data from the DUO-O trial provide encouraging evidence for this Lynparza and Imfinzi combination in patients without tumor BRCA mutations and reinforce our continued commitment to finding new treatment approaches for these patients. It will be important to understand the key secondary endpoints as well as data for relevant subgroups,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in the release.

Enrollment for the DUO-O Trial

The international DUO-O trial is currently being conducted in more than 150 cancer treatment centers.

According to the study’s listing on clinicaltrials.gov, there are 1,374 patients enrolled, who have stage 3 or 4 high-grade epithelial ovarian cancer, which can include high-grade serous, high-grade endometrioid, clear cell ovarian cancer or carcinoma, primary peritoneal cancer and/or fallopian tube cancer. Patients must not have received prior treatment for their cancer, though they should be candidates for surgery, and it is required that patients either be menopausal or have a negative pregnancy test, and that they know their BRCA mutational status.

All participants were randomly assigned to one of three treatment groups:

• Platinum-based chemotherapy plus Avastin and a placebo, followed by maintenance therapy with Avastin and placebo
• Platinum-based chemotherapy plus Lynparza and Imfinzi followed by maintenance Avastin, Imfinzi and Lynparza placebo
• Platinum-based chemotherapy plus Avastin and Imfinzi followed by maintenance Avastin, Lynparza and Imfinzi

Since DUO-O is a randomized trial, neither patients nor their treating clinicians know which of the three regimens are being administered.

While the interim analysis of the data appears to be promising, according to AstraZeneca, primary outcome data is planned to be collected in June 2023, with the overall study completion date planned for May 2028.

Mechanism of Action

Imfinzi, which is the current standard of care for certain patients with unresectable stage 3 non-small cell lung cancer, works by blocking the PD-L1 protein, which plays a role in the tumor cells’ ability to hide from the immune system. Once PD-L1 is blocked, the patients’ immune system can better find and fight the cancer.

READ MORE: Imfinzi-Based Treatment Before, After Surgery May Significantly Improve Survival in Resectable NSCLC

Lynparza, on the other hand, works a bit differently. It belongs to a class of drugs called PARP inhibitors, which inhibits cancers’ means of DNA damage repair, eventually causing cancer cell death. The drug has already been granted approval by the Food and Drug Administration for certain types of ovarian and breast cancers.

READ MORE: FDA’s Extension of Lynparza Approval an ‘Exciting Thing’ for Certain Patients With Breast Cancer
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