Lynparza + bevacizumab, and as monotherapy, demonstrates clinically meaningful long-term survival in certain patients with first-line advanced ovarian cancer in two phase III trials.- AstraZeneca + Merck Inc.

Five-year follow-up and final OS results from Phase III PAOLA-1 trial (abstract #LBA29) :The Phase III PAOLA-1 trial evaluated Lynparza in combination with bevacizumab as first-line maintenance therapy in patients with advanced ovarian cancer, who were without evidence of disease after surgery or following response to platinum-based chemotherapy. Final overall survival (OS), a key secondary endpoint, in those who received Lynparza plus bevacizumab was 56.5 months versus 51.6 months with bevacizumab alone (HR=0.92 [95% CI, 0.76-1.12]; p=0.4118) in patients with newly diagnosed advanced ovarian cancer. These OS results were not statistically significant. In an exploratory subgroup analysis of HRD-positive patients, Lynparza plus bevacizumab provided a clinically meaningful improvement in OS, reducing the risk of death by 38% (HR=0.62 [95% CI, 0.45-0.85]) versus bevacizumab alone. 65.5% of patients who received Lynparza plus bevacizumab were still alive at five years versus 48.4% who received bevacizumab alone. Lynparza plus bevacizumab also improved median progression-free survival (PFS) to nearly four years (46.8 months) versus 17.6 months with bevacizumab plus placebo, and 46.1% of patients who received Lynparza in combination with bevacizumab remain progression free versus 19.2% of patients who received bevacizumab alone. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals. Adverse events of special interest for Lynparza in combination with bevacizumab versus bevacizumab alone included myelodysplastic syndrome/acute myeloid leukemia/aplastic anemia (1.7% vs. 2.2%), new primary malignancies (4.1% vs. 3.0%) and pneumonitis/interstitial lung disease/bronchiolitis (1.3% vs. 0.7%).

Seven-year follow-up from Phase III SOLO-1 trial (abstract #517O) : The Phase III SOLO-1 trial evaluated Lynparza as monotherapy as first-line maintenance therapy in patients with advanced ovarian cancer, who were without evidence of disease after surgery or following response to platinum-based chemotherapy. In the trial, Lynparza demonstrated a clinically meaningful improvement in OS versus placebo in patients with germline BRCA-mutated (gBRCAm) newly diagnosed advanced ovarian cancer, reducing the risk of death by 45% (HR=0.55 [95% CI, 0.40-0.76]; p=0.0004) versus placebo (not statistically significant). Median OS was not reached with Lynparza versus 75.2 months with placebo. At the seven-year descriptive OS analysis, 67% of Lynparza patients were alive versus 47% of placebo patients (44% of whom had a subsequent PARP inhibitor), and 45% of Lynparza patients versus 21% of placebo patients were alive and had not received a first subsequent treatment.

Additional data showed median time to first subsequent therapy (TFST) was 64.0 months with Lynparza versus 15.1 months with placebo. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals. The most common treatment-emergent adverse events (?20%) were nausea (78%), fatigue (64%), vomiting (40%), anemia (40%), diarrhea (35%), arthralgia (29%), constipation (28%), abdominal pain (26%), headache (23%), neutropenia (23%), dysgeusia (22%), dizziness (20%) and decreased appetite (20%).

Professor Isabelle Ray-Coquard, principal investigator from the PAOLA-1 trial and president of the GINECO group said, “For women facing an advanced ovarian cancer diagnosis who are HRD-positive, a targeted treatment in the first-line maintenance setting is critical to helping them live longer. These latest results at the five-year landmark demonstrate that olaparib with bevacizumab reduces the risk of death by 38% in HRD-positive patients compared to bevacizumab alone, further reinforcing the clinically meaningful long-term survival benefit of this combination. This should be promising news for both clinicians and patients, as we see these additional data show that this combination may allow patients more time with family and loved ones. These results also highlight the importance of biomarker testing as part of a precision medicine approach to guide treatment decisions in ovarian cancer patients.”

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, “Historically, the five-year survival rate of newly diagnosed patients with advanced ovarian cancer is 30-50%. In that context, it is phenomenal to share the long-term overall survival data from both PAOLA-1 and SOLO-1, with two out of three patients still alive in these trials. We continue to believe in LYNPARZA’s ability to help biomarker-selected patients with advanced ovarian cancer to achieve better outcomes.”

See-"Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial."-Paul DiSilvestro , MD; Susana Banerjee , MD, PhD; Nicoletta Colombo , MD, PhD; Giovanni Scambia , MD; Byoung-Gie Kim, MD, PhD; Ana Oaknin , MD, PhD; DOI: 10.1200/JCO.22.01549 Journal of Clinical Oncology .Published online September 09, 2022.