In a phase III trial (EPIK-O/ENGOT-ov61) reported in the Journal of Clinical Oncology, Konstantinopoulos et al compared the survival outcomes of alpelisib plus olaparib vs single-agent chemotherapy in patients with platinum-resistant or -refractory high-grade serous ovarian cancer (HGSOC) with no BRCA mutation.
Study Details
In the international open-label trial, 358 patients were randomly assigned to receive alpelisib at 200 mg once daily and olaparib at 200 mg twice daily (n = 180) or physician choice of single-agent chemotherapy with paclitaxel at 80 mg/m2 once weekly or pegylated liposomal doxorubicin at 40 to 50 mg/m2 once every 28 days (n = 178). Patients had received one to three previous systemic therapies; prior bevacizumab was required (unless contraindicated), and prior PARP inhibitor treatment was permitted. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival on blinded independent review committee assessment.
Key Findings
At data cutoff (in April 2023), median follow-up for progression-free survival was 9.3 months (range = 2.8–20.3 months). Median progression-free survival was 3.6 months (95% confidence interval [CI] = 3.4–4.3 months) with alpelisib plus olaparib vs 3.9 months (95% CI = 3.7–5.4 months) with chemotherapy (hazard ratio [HR] = 1.14, 95% CI = 0.88–1.48, P = .84).
Objective response rate was 15.6% (95% CI = 10.6%–21.7%) vs 13.5% (95% CI = 8.8%–19.4%). Median duration of response was 7.4 months (95% CI = 5.0–12.9 months) vs 5.6 months (95% CI = 3.8 months to not evaluable). Median overall survival was 10.0 vs 10.6 months (HR = 1.22, 95% CI = 0.87–1.71).
Response to alpelisib plus olaparib was associated with AKT2 amplification (P = .04). AKT2 amplification was associated with homologous repair deficiency–negative status (P = .008).
The most common adverse events of any grade in the alpelisib plus olaparib group were nausea (61.7%) and hyperglycemia (52.2%). The most common grade 3 or 4 adverse events were hyperglycemia (18.9%) and vomiting (10.0%). Serious adverse events occurred in 51.1% of those given alpelisib plus olaparib vs 30.5% of those given chemotherapy. Adverse events led to a discontinuation of treatment in 14.4% vs 7.3% of patients. One treatment-related death (from pneumonia) was reported in the group given alpelisib plus olaparib.
The investigators concluded: “The primary objective, [progression-free survival] improvement, was not met in EPIK-O. No new or unexpected adverse events were observed. Biomarker analyses provided new insights for responders to alpelisib plus olaparib.”
Panagiotis A. Konstantinopoulos, MD, PhD, of Dana-Farber Cancer Institute, Boston, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Novartis Pharmaceuticals Corporation. For full disclosures of all study authors, visit ascopubs.org.
