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Combining olaparib with standard bevacizumab significantly improved progression-free survival compared with bevacizumab alone as frontline maintenance therapy in women with advanced ovarian cancer, regardless of BRCA status, according to topline results from the phase III PAOLA-1 trial.
José Baselga, MD
Combining olaparib (Lynparza) with standard bevacizumab (Avastin) significantly improved progression-free survival (PFS) compared with bevacizumab alone as frontline maintenance therapy in women with advanced ovarian cancer, regardless of BRCA status, according to topline results from the phase III PAOLA-1 trial.1
AstraZeneca and Merck (MSD), the codevelopers of olaparib, reported in a press release that the results from PAOLA-1 will be presented at an upcoming medical conference. The companies also noted that the safety and tolerability data were consistent with results previously reported for the agents.
“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 a BRCA gene 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 R&D, of AstraZeneca, stated in the press release.
The double-blind phase III PAOLA-1 trial accrued patients with newly-diagnosed advanced FIGO stage III/IV high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer, who reached a complete or partial response to first-line therapy with bevacizumab and platinum-based chemotherapy. Patients were randomized to frontline maintenance with olaparib plus bevacizumab or bevacizumab alone. The primary endpoint was PFS.
In December 2018, the FDA approved olaparib monotherapy as a frontline maintenance treatment for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.
The approval was based on findings from the phase III SOLO-1 trial, in which olaparib reduced the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001) compared with placebo following platinum-based chemotherapy.2
The phase III SOLO-1 trial evaluated maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. Patients with newly diagnosed, FIGO stage III-IV, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations were enrolled. These patients must have also received cytoreductive surgery, and be in clinical complete response or partial response after platinum-based chemotherapy.
The study treatment in SOLO-1 continued until disease progression, and treatment was ceased for patients with no evidence of disease at 2 years. However, patients with a partial response at 2 years could continue treatment.
Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.
Results showed that, at a median follow-up of 41 months, the median PFS by independent central review was not reached in the olaparib arm (n = 260), versus 14.1 months in the placebo arm (n = 131). The investigator-assessed PFS in the olaparib arm was not reached, compared with 13.8 months in the placebo arm (HR, 0.30; 95% CI, 0.23-0.41; P <.0001). The median PFS for olaparib has not yet been reached.
Additionally, patients who received olaparib maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72; P =.0002). Overall survival data are not yet mature. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the olaparib arm was 12%.
Adverse events (AEs) observed were low-grade, with the most common grade ≥3 AEs in the olaparib arm being anemia (22%) and neutropenia (8%). Baseline characteristics, including health-related quality-of-life scores, were balanced between the 2 arms.
In the press release, Roy Baynes MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, commented on how the PAOLA-1 results build on the SOLO-1 findings.
“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.”