The addition of cediranib to olaparib did not result in improved progression-free survival in comparison with platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer, which was the primary end point of the phase III NRG-GY004 trial, according to a press release from AstraZeneca and Merck.
Jose Baselga, MD, PhD
Jose Baselga, MD, PhD
The addition of cediranib to olaparib (Lynparza) did not result in improved progression-free survival (PFS) in comparison with platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer, which was the primary end point of the phase III NRG-GY004 trial, according to a press release from AstraZeneca and Merck (MSD).1
Safety and tolerability profiles for the combination were considered to be more or less consistent with the known profiles for the individual agents. Full findings from the trial will be presented at a future medical meeting.
“Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer. We will work closely with NRG Oncology and the [National Cancer Institute] to review the full results to inform our ongoing research,” José Baselga, MD, PhD, executive vice president of oncology research and development, AstraZeneca, said in the press release.
The open-label, randomized, multicenter phase III trial is exploring the safety and efficacy of the VEGF and PARP inhibitor combination versus olaparib alone or versus standard chemotherapy in women with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.
Patients were eligible for the trial if they had acceptable organ function levels, an ECOG performance status of 0 to 2, and had adequately controlled blood pressure. Acceptable prior therapies included platinum-based chemotherapy, hormonal therapy, and nonplatinum-based chemotherapy in the recurrent setting. Toxicities from prior treatments must have resolved to a grade 1 or less. Additionally, patients could enroll whether or not they had aBRCAmutation.
Participants could not have received a previous PARP or VEGF inhibitor or any other recent investigational agent. Additionally, those with a history of gastrointestinal perforation, intra-abdominal abscess, cardiac risk factors, stroke or recent transient ischemic attack, HIV, vascular disease, hypertensive crisis or encephalopathy, or other invasive malignancies were ineligible for the trial.
In the experimental combination arm, patients received oral olaparib twice daily with cediranib maleate given orally daily in 28-day cycles continuously until there was evidence of disease progression or unacceptable toxicity. In the control arm, patients received either paclitaxel, gemcitabine hydrochloride, or pegylated liposomal doxorubicin hydrochloride, all given with carboplatin chemotherapy.
The primary end point was PFS in the intention-to-treat (ITT) population; secondary end points included overall survival (OS), safety, and patient-reported outcomes.
“Ovarian cancer is one of the most difficult tumors to diagnose and treat early. AstraZeneca, MSD and our partners will continue to explore ways to help patients through our joint clinical trial development program,” Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, MSD Research Laboratories, said in the press release.
NRG-GY004 was a confirmatory trial to a phase II trial of the combination regimen in patients with recurrent platinum-sensitive ovarian cancer, which showed a doubling of PFS time induced by the combination regimen in comparison with olaparib alone.2
The phase II trial randomized patients 1:1 to receive either the cediranib/olaparib combination (n = 44) or olaparib monotherapy (n = 46). The median PFS in the ITT population was 16.5 months with the doublet versus 8.2 months in the olaparib-alone arm (HR, 0.50; 95% CI, 0.30-0.83;P= .007). The median OS was 44.2 months versus 33.3 months for the combination and monotherapy arms, respectively (HR, 0.64; 95% CI, 0.36-1.11;P= .11).
Patients who did not harborBRCAmutations (n = 42) showed a significant benefit from the addition of cediranib, with a median PFS of 23.7 months versus 5.7 months without cediranib (HR, 0.32;P= .002), and a median OS of 37.8 months versus 23.0 months without (HR, 0.48;P= .074).
Olaparib is currently approved for use as a first-line maintenance therapy for patients withBRCA-mutated advanced ovarian cancer after receiving platinum-based chemotherapy.