5-Year Follow-up from Phase 3 SOLO-1 Continues to Show Long-Term PFS with Olaparib

Five-year follow-up data from the phase 3 SOLO-1 trial demonstrated a long-term progression-free survival (PFS) benefit with olaparib (Lynparza) versus placebo as a first-line maintenance treatment in patients with newly diagnosed, advanced BRCA-mutated (BRCAm) ovarian cancer who had a complete or partial response following platinum-based chemotherapy, according to AstraZeneca, the co-developer of the agent.

The results from this trial were presented during the 2020 European Society of Medical Oncology virtual congress.

“For patients with newly-diagnosed BRCA-mutated advanced ovarian cancer, the benefit derived from two years of maintenance treatment with [olaparib] continued long after treatment ended,” study investigator Susana Banerjee, MBBS, MA, PhD, FRCP, consultant medical oncologist at The Royal Marden NHS Foundation Trust and reader at The Institute of Cancer Research in London, said in a press release. “After 5 years, almost half of women were free of cancer progression. These results represent a significant step forward in the treatment of BRCA-mutated advanced ovarian cancer.”

The phase 3, randomized, double-blinded, placebo-controlled, multicenter trial evaluated the efficacy and safety of olaparib tablets at a dose of 300 mg twice daily as a maintenance monotherapy compared with placebo in patients with newly-diagnosed BRCAm advanced ovarian cancer following first-line platinum-based chemotherapy. Patients were randomized 2:1 to receive either Olaparib or placebo for up to 2 years or until disease progression. However, those who had a partial response at 2 years were permitted to remain on therapy at the investigator’s discretion.

Overall, the trial randomized 391 patients with a deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. The primary end point was PFS and key secondary end points included time to second disease progression or death, time to first subsequent treatment, and overall survival (OS).

The 5-year follow-up data demonstrated that olaparib reduced the risk of disease progression or death by 67% (HR, 0.33; 95% CI, 0.25-0.43) and improved PFS to a median of 56.0 months versus 13.8 months for placebo. Moreover, at 5 years, 48.3% of patients treated with olaparib remained free from disease progression versus 20.5% on placebo. The median duration of treatment with olaparib was 24.6 months versus 13.9 months with placebo.

“Once a patient’s ovarian cancer recurs, it historically has been incurable. Even at an advanced stage, we have shown that maintenance treatment with [olaparib] can help patients achieve sustained remission,” José Baselga, MD, PhD, executive vice president of Oncology R&D, said in the release. “Today’s results further underline the critical importance of identifying a patient’s biomarker status at the time of diagnosis to offer a treatment that may help delay disease progression.”

In addition, the safety profile observed with olaparib in this trial was consistent with previous observation. The most common adverse events (AEs) seen in 20% or more of the trial participants were nausea (77%), fatigue/asthenia (63%), vomiting (40%), anemia (39%), and diarrhea (34%). Further, the most common grade 3 or higher AEs were anemia (22%) and neutropenia (9%). In total, 12% of patients on olaparib discontinued treatment due to an AE.

Notably, the phase 3 SOLO-1 trial met the primary end point of PFS in June 2018, which formed the basis of approvals in the US, EU, Japan, China, as well as several other countries.

Olaparib is currently approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. The agent is also approved in the US and several other countries for the treatment of germline BRCA-mutated metastatic pancreatic cancer. Even further, olaparib is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. Regulatory reviews remain underway in several countries for ovarian, breast, pancreatic, and prostate cancers.

Reference:

Lynparza improved median time patients lived without disease progression to over four and half years in BRCA-mutated advanced ovarian cancer vs. just over one year with placebo [news release]. Published September 18, 2020. Accessed September 18, 2020. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/lynparza-improved-median-time-patients-lived-without-disease-progression-to-over-four-and-half-years-in-BRCA-mutated-advanced-ovarian-cancer.html