AstraZeneca’s lead poly ADP-ribose polymerase (PARP) inhibitor Lynparza has shown promise its key SOLO-2 phase 3 trial.
The study compared the use of Lynparza as a stand-alone treatment in patients with germline BRCA-mutated, platinum-sensitive, relapsed ovarian cancer.
Compared to a placebo, twice daily 300mg Lynparza therapy met its primary endpoint of investigator assessed progression-free survival (PFS), resulting in a median PFS of 19.1 months versus 5.5 months in the control group.
PFS measured by Blinded Independent Central Review evaluation – a pre-specified analysis supporting the primary endpoint – was 30.2 months for Lynparza compared to 5.5 months for a placebo. Therefore, the total improvement was 24.7 months.
Lynparza’s safety profile was consistent with that seen in its capsule formulation, resulting in 36.9% of patient reporting non-haematological adverse events compared to 18.2% given a placebo. A total of 75.9% reported nausea, 65.6% reported fatigue/asthenia, and 37.4% reported vomiting.
In terms of adverse haematological events, the most common were anaemia (43.6%), neutropenia (19.5%), and thrombocytopenia (13.8%).
“Today’s results are very encouraging, as they build upon previous trials examining Lynparza in platinum-sensitive relapsed BRCA-mutated ovarian cancer,” said Eric Pujade-Lauraine, principal investigator of SOLO-2. “Most importantly, patients were able to maintain quality of life while experiencing an impressive delay in disease progression, demonstrating the benefits of Lynparza tablets for these women whose cancer is often difficult to treat.”
Sean Bowen, executive vice president of Global Medicines Development at AZ noted that the twice daily 300mg dose could offer patients a drastically reduced pill burden from 16 tablets per day to four.
Lynparza is currently FDA approved as a monotherapy in the form of 400mg tablets for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer patients who have been treated with three or more lines of chemotherapy. The approval was made under accelerated approval based on objective response rate and duration of response.
The drug exploits defective DNA damage repair mechanisms found in cancer cells which have a mutated BRCA gene. The defective gene means BRCA-mutated cells rely on PARP to fix breaks in DNA strands, however, with the introduction of a PARP inhibitor like Lynparza, strand breaks accumulate, eventually leading to cancer cell death.
The impressive SOLO-2 results follow similar success in Lynparza’s phase 3 OLYMPIAD trial where it demonstrated superior PFS to either capecitabine, vinorelbine or eribulin chemotherapy in HER-2-negative, metastatic breast cancer patients with BRCA1 or BRCA2 mutations.