AstraZeneca’s Lynparza in combination or as a monotherapy demonstrates meaningful survival benefit in long-term follow-up.
Long-term follow-up results from the PAOLA-1 (NCT02477644) and SOLO-1 (NCT01844986) phase 3 trials of olaparib (Lynparza; AstraZeneca, MSD) with or without bevacizumab demonstrated clinically meaningful improvements in overall survival (OS).
The findings showed class-leading progression-free survival (PFS) in combination with bevacizumab for individuals with positive homologous recombination deficiency (HRD) compared with an active comparator, bevacizumab, and as a monotherapy for individuals with BRCA mutations and compared with the placebo, respectively.
“These latest results at the 5-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,” Isabelle Ray-Coquard, MD, PhD, president of the Gineco group, said in a statement. “These results also highlight the importance of biomarker testing as part of a precision medicine approach to guide treatment decisions in ovarian cancer patients.”
The updated results from the PAOLA-1 phase 3 trial demonstrated that olaparib plus bevacizumab increased the median OS to 56.5 months compared with 51.6 months with bevacizumab alone.
However, the increase was not statistically significant, investigators said.
In individuals who are HRD-positive, olaparib and bevacizumab provided a clinically meaningful improvement in OS by 38% compared with bevacizumab alone, despite the trial enrolling 30% of individuals who were stage 4.
Additionally, 65.5% of individuals treated with olaparib with bevacizumab were still alive at 5 years compared with just 48.4% of individuals who were treated with bevacizumab alone.
The median PFS also improved to 46.8 months compared with 17.6 months with bevacizumab, plus the placebo. At 5 years, 46.1% of individuals treated with the combination remained progression free compared with 19.2% with bevacizumab alone.
The updated results from the SOLO-1 phase 3 trial demonstrated a clinically meaningful improvement in OS compared with the placebo in individuals with BRCA-mutated newly diagnosed ovarian cancer. It also reduced the risk of death by 45%.
The median OS was still not reached with olaparib compared with 75.2 months with the placebo. At the 7-year descriptive OS analysis, 67% of individuals taking olaparib were alive compared with 47% of individuals taking the placebo.
Further, approximately 45% of individuals taking olaparib were alive and did not receive a first subsequent treatment compared with 21% of those on the placebo.
Additional data showed that the median time to first subsequent therapy with olaparib was 64 months compared with 15.1 months with the placebo.
Both trials were conducted in biomarker-selected and newly diagnosed individuals with advanced ovarian cancer in the first-line maintenance setting and demonstrated a consistent safety profile.
Olaparib is approved as maintenance treatment of platinum-sensitive relapsed ovarian cancer and as a monotherapy and in combination with bevacizumab for the first-line maintenance treatment of individuals with BRCA-mutated and HRD-positive advanced ovarian cancer, respectively.
The results of both studies were presented at the 2022 European Society of Medical Oncology. The results of the SOLO-1 study were published in Journal of Clinical Oncology.
Landmark 5-year follow-up of PAOLA-1 phase III trial demonstrated Lynparza plus bevacizumab meaningfully extended survival with 65.5% of HRD-positive patients surviving 5 years vs. 48.4% treated with bevacizumab and placebo. News release. AstraZeneca. September 9, 2022. Accessed September 16, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-in-combination-with-bevacizumab-demonstrates-clinically-meaningful-survival-benefit-in-advanced-ovarian-cancer.html