Olaparib and Bevacizumab Meet PFS Endpoint as Frontline Maintenance in Phase III Ovarian Cancer Trial

Jose Baselga, MD, PhD

Jose Baselga, MD, PhD

Olaparib (Lynparza) in combination with bevacizumab (Avastin) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as a frontline maintenance regimen compared with bevacizumab alone in women with advanced ovarian cancer, according to early results from the phase III PAOLA-1 trial.

In a press release, AstraZeneca and Merck (MSD), the companies jointly developing and commercializing olaparib, announced that this met the primary endpoint for the trial in the intent-to-treat population.

“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. Following positive results from the SOLO-1 trial for women with aBRCAgene mutation, the PAOLA-1 trial marks yet another positive phase III 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,” José Baselga, MD, PhD, executive vice president, Oncology Research & Development, AstraZeneca, said in the press release.

The safety profile was also consistent with previous reports of both agents. Further findings from the PAOLA-1 trial, including subgroup analyses, will be presented at an upcoming medical meeting.

“The phase III PAOLA-1 trial demonstrates MSD’s and AstraZeneca’s continued commitment to improving clinical outcomes for women with advanced ovarian cancer. In this co-operative group trial sponsored by ARCAGY Research, maintenance treatment with Lynparza when added to a standard-of-care treatment was evaluated in an environment representative of real clinical practice. By studying Lynparza in this broader patient population, we have learned more about how it may help even more patients with advanced ovarian cancer in the future,” Roy Baynes, senior vice president, head of global clinical development, and chief medical officer, MSD Research Laboratories, said in a statement.

The ongoing randomized, double-blind trial is exploring the use of olaparib or placebo in combination with bevacizumab as a maintenance regimen following first-line therapy for women with advanced FIGO stage IIIB to IV, high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer (NCT02477644).

Approximately 806 patients who had achieved a complete or partial response to first-line treatment with platinum-taxane chemotherapy and bevacizumab were enrolled in the trial, regardless ofBRCAstatus. Patients did undergoBRCAtesting in the study for stratification.

The patients must have received 6 to 9 cycles of platinum-based chemotherapy and at least 3 cycles of bevacizumab, at 15 mg/kg every 3 weeks, in combination with the last 3 cycles of chemotherapy to be eligible for the trial. Additionally, patients must have normal organ and bone marrow function, an ECOG performance status of 0 or 1, and resolution of prior adverse events to grade 1 or better before beginning maintenance. Randomization was supposed to occur between 3 and 9 weeks from the last dose of chemotherapy.

Those with mucinous carcinoma or tumors of low malignant potential were not eligible for enrollment as well as those with serous or clear cell adenocarcinoma or carcinosarcoma. Patients with other malignancies within 5 years, significant cardiovascular disease, hemorrhagic disorders within 6 months, brain metastases or spinal cord compression, central nervous system disease, known active hepatitis, or bowel obstruction were also ineligible for enrollment.

Participants were all randomized 2:1 to receive 300 mg of olaparib twice daily or placebo for up to 2 years.

The primary endpoint of the PAOLA-1 trial is PFS, and secondary endpoints include overall survival, time to earliest progression by RECIST or CA-125, second PFS, time to start of first subsequent therapy or death, time to start of second subsequent therapy or death, safety, and patient-reported outcomes.

Reference:

Lynparza Phase III PAOLA-1 trial met primary endpoint as 1st-line maintenance treatment with bevacizumab for advanced ovarian cancer [press release]. Kenilworth, NJ: AstraZeneca and MSD Inc; August 14, 2019. https://bit.ly/2Z2endB. Accessed August 14, 2019.