Everolimus/fulvestrant combination improves PFS in HR-positive breast cancer
Adding everolimus to fulvestrant in second-line treatment of hormone receptor (HR)-positive, HER2-negative advanced breast cancer improves progression-free survival (PFS) by 40 percent, the phase II PrECOG 0102 study has shown. [SABCS 2016, abstract S1-02]
“Current treatment options for patients with HR-positive, HER2-negative advanced breast cancer who progress on first-line aromatase inhibitor [AI] therapy include the combination of the mTOR inhibitor everolimus and the steroidal AI exemestane, as well as the selective oestrogen receptor down-regulator fulvestrant,” said lead investigator Dr Noah Kornblum of the Albert Einstein College of Medicine, New York, US. “We hypothesized that everolimus in combination with fulvestrant would be more effective than fulvestrant alone in this context.”
The study included 130 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who were resistant to first-line AI therapy. They were randomized to receive fulvestrant (500 mg every 2 weeks for 3 doses, then every 4 weeks) with or without everolimus (10 mg) for 48 weeks. Patients who were still on treatment at 48 weeks continued treatment until disease progression. Tumour assessment was performed at baseline and every 12 weeks.
Patients in this study had Eastern Cooperative Oncology Group performance status of either 0 or 1 (59 vs 41 percent), and the median age was 61 years.
“Results showed that adding everolimus to fulvestrant significantly improved PFS by 40 percent compared with fulvestrant alone. Median PFS was 10.4 months in patients receiving the everolimus/fulvestrant combination vs 5.1 months in patients receiving fulvestrant alone [hazard ratio, 0.60; p=0.02],” reported Kornblum.
Interestingly, the median PFS in both the experimental and control arms appeared to be longer than that in BOLERO-2, a phase III study comparing the efficacy of everolimus plus the AI exemestane vs exemestane alone in a similar patient population and setting (7.8 vs 3.2 months; p<0.0001). [Adv Ther 2013;30:870-884] “In my opinion, these PFS differences may be due to the superiority of high-dose fulvestrant over exemestane,” suggested Kornblum.
In PrECOG 0102, grade 3 adverse events (AEs) were more common in the combination arm (48 percent vs 14 percent in the fulvestrant arm). The most common grade 3 AEs in the combination arm were stomatitis (9 percent), pneumonitis (6 percent), hyperglycaemia (6 percent) and fatigue (5 percent). Notably, prophylactic corticosteroid mouthwash was not used in this study to reduce the risk of stomatitis.
“The safety profile of the everolimus/fulvestrant combination was similar to that of the everolimus/exemestane combination as shown in the BOLERO-2 trial,” noted Kornblum.
“We need larger studies to confirm the efficacy and safety of adding everolimus to fulvestrant in AI-resistant advanced breast cancer,” he concluded. “However, no phase III trial has been planned or is underway for this combination.”