Novartis recently announced the final overall survival (OS) analysis results of the phase III SOLAR-1 study of the new breast cancer drug Piqray (alpelisib) at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress. Data showed that in patients with advanced breast cancer (aBC) harboring PIK3CA mutation and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), compared with the fulvestrant monotherapy group, the Piqray plus fulvestrant combination therapy group achieved a clinically relevant improvement of 8 months in OS, and the OS improvement in patients with lung or liver metastases reached more than 14 months. Lung and liver metastases are observed in 41% of postmenopausal women with HR+aBC and are considered more aggressive and therapeutically challenging.
Background of PIK3CA Mutation in Advanced Breast Cancer
The data presented at this ESMO Congress provides increasing evidence of the efficacy of Piqray in the treatment of aBC patients with PIK3CA mutation. Globally, 334,000 people are diagnosed with advanced breast cancer (aBC) each year. Approximately 40% of patients with HR+/HER2- subtype have PIK3CA mutation, which stimulates tumor growth and is associated with poor treatment response and poor prognosis.
Previously Published Efficacy Data
Previously published data showed that compared with fulvestrant alone, Piqray plus fulvestrant treatment nearly doubled progression-free survival (median PFS: 11.0 months vs 5.7 months), significantly reduced the risk of disease progression or death by 35% (HR=0.65, 95% CI: 0.50-0.85; p<0.001), and more than doubled the overall response rate (ORR: 36% vs 16%). Subgroup analysis of PFS showed consistent efficacy of Piqray regardless of the presence or absence of lung/liver metastases. In patients without PIK3CA mutation, the combination of Piqray plus fulvestrant did not show a significant improvement in PFS.
Final OS Results Presented at ESMO Congress
Data presented at this ESMO Congress showed that compared with the fulvestrant monotherapy group, the Piqray plus fulvestrant combination therapy group achieved a clinically relevant improvement of 8 months in overall survival (OS) (median OS: 39.3 months vs 31.4 months; one-sided p≤0.0161; HR=0.86; 95% CI: 0.64-1.15; p=0.15). This difference did not reach the statistical significance threshold. The OS improvement in patients with lung or liver metastases exceeded 14 months, which means a more significant benefit in patients with more severe disease (median OS: 37.2 months vs 22.8 months; HR=0.68; 95% CI: 0.46-1.00).
Additional Efficacy Benefits
In addition, data showed that compared with the fulvestrant monotherapy group, the time to chemotherapy was delayed by 9 months in the Piqray plus fulvestrant group (23.3 months vs 14.8 months; HR=0.72; 95% CI: 0.54-0.95), and the quality of life (QOL) was maintained.
Safety Profile
In terms of safety, no new safety signals were observed, and adverse events were consistent with previously reported results.
