Lynparza-Avastin Combo Cuts Risk of Disease Progression, Death in Advanced OC, Phase 3 Trial Shows

When added to Avastin (bevacizumab), Lynparza (olaparib) reduces the risk of disease progression and death in women with advanced forms of ovarian cancer who are responding to their first-line treatment with platinum-based chemotherapy, a Phase 3 trial shows.

Lynparza is an oral anti-cancer treatment jointly developed by AstraZeneca and Merck (known as MSD outside the United States and Canada) for the treatment of advanced forms of ovarian, pancreatic, and certain types of breast cancer.

It works by inhibiting the activity of an enzyme called PARP, which is involved in DNA repair and cancer cells’ survival and proliferation. The medication has been found to be particularly effective in patients carrying genetic mutations in either BRCA1 or BRCA2, two tumor-suppressor genes that play a role in DNA repair.

The randomized, double-blind, PAOLA-1 Phase 3 trial (NCT02477644) is currently assessing the effectiveness of Lynparza in combination with Avastin as a first-line maintenance therapy for women with advanced forms of ovarian cancer, with or without BRCA mutations, who had previously responded to treatment with platinum-based chemotherapy.

Women in the trial were randomly assigned to receive either Lynparza tablets (300 mg twice a day) in combination with Avastin, or Avastin alone. The trial’s primary endpoint was to assess the percentage of women alive and whose disease did not worsen after 15 months of treatment. Secondary endpoints included assessments of overall survival, time to disease progression, treatment safety, and tolerability.

New data from PAOLA-1 recently announced by AstraZeneca and Merck have shown the trial met its primary endpoint, with a significantly higher proportion of women treated with the Lynparza-Avastin combo therapy showing no signs of disease progression, compared to those treated with Avastin alone.

In addition, the safety and tolerability profile of the combo therapy was consistent with what had previously been reported for each medication separately.

Both companies are planning to present the full data from PAOLA-1, including additional biomarker subgroup analyses, at a future medical meeting.

PAOLA-1 is the second Phase 3 trial — after SOLO-1 (NCT01844986) — whose findings support the use of Lynparza as a first-line maintenance treatment for patients with advanced ovarian cancer.

“The positive results from the PAOLA-1 trial demonstrate a clear potential benefit of adding Lynparza to the standard treatment bevacizumab for women with advanced ovarian cancer,” José Baselga, executive vice president of oncology research and development at AstraZeneca, said in a press release.

“Following positive results from the SOLO-1 trial for women with a BRCA gene mutation, the PAOLA-1 trial marks yet another positive Phase 3 trial for Lynparza as a first-line maintenance treatment for women with advanced ovarian cancer. We look forward to discussing the results with global health authorities as soon as possible,” Baselga said.

PAOLA-1 is part of the European Network for Gynecological Trial (ENGOT) research network and has been sponsored by the Association de Recherche sur les Cancers dont Gynecologiques (ARCAGY) Research, on behalf of the Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein (GINECO).

ARCAGY-GINECO represents an academic group of researchers who specialize in clinical and translational research specifically focused on female cancers. Both are part of the Gynecologic Cancer InterGroup (GCIC).

“The PAOLA-1 trial is a positive example of the strength and promise of academia-industry collaboration in advancing science and new treatment options for patients. We greatly appreciate the commitment of AstraZeneca and Merck in working with academic cooperative groups in ENGOT and look forward to sharing the full PAOLA-1 results at a forthcoming medical meeting,” said Eric Pujade-Lauraine, medical director of ARCAGY Research.