Piqray Plus Faslodex Improves PFS in Advanced Breast Cancer

Piqray (alpelisib) plus Faslodex (fulvestrant) showed a significant and clinically meaningful improvement in progression-free survival (PFS) compared with Faslodex alone in patients with CDK4/6 inhibitor–pretreated, PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer, meeting the primary end point of the phase 3 EPIK-B5 study.

Findings presented during the 2025 San Antonio Breast Cancer Symposium demonstrated that, as of the data cutoff of October 15, 2024, the median PFS per RECIST 1.1 criteria by blinded independent central review (BICR) among patients who received Piqray plus Faslodex (94 patients) was 7.4 months versus 2.8 months with placebo plus Faslodex (94 patients). The overall response rates (ORRs) per BICR were 23.4% and 4.3%, respectively.

“EPIK-B5 met its primary end point, demonstrating a PFS improvement that was statistically significant and clinically meaningful in patients with hormone receptor–positive, HER2-negative PIK3CA-mutated [disease] who progressed on previous treatment with CDK4/6 inhibitors,” Dr. Michelino De Laurentiis, the chair of the Department of Breast and Thoracic Oncology at National Cancer Institute IRCCS "Fondazione Pascale" in Napoli, Italy said during the presentation.

In May 2019, the FDA approved Piqray plus Faslodex for the treatment of postmenopausal women and men with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. The regulatory decision was supported by data from the phase 3 SOLAR-1 trial which showed that patients who received the combination achieved a significant PFS benefit compared with those who received Faslodex alone.

How was the study designed?

EPIK-B5 enrolled adult postmenopausal women and men with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who experienced disease progression or relapse on or after treatment with a CDK4/6 inhibitor and an aromatase inhibitor. Patients were required to have at least 1 measurable lesion per RECIST 1.1 criteria as assessed by the investigator, have received no more than 1 prior line of chemotherapy, excluding neoadjuvant/adjuvant chemotherapy, and adequate tumor tissue for PIK3CA mutational status assessment by a central laboratory.

Patients were randomly assigned 1:1 to receive Piqray at 300 mg in combination with Faslodex at 500 mg or placebo plus Faslodex. Crossover to the combination arm was permitted at the time of disease progression per RECIST 1.1 criteria by BICR.

The primary end point was PFS per BICR. Secondary end points included ORR, duration of response, and time to response based on BICR assessment. Overall survival (OS), safety, ECOG performance status, quality, and time to second disease progression were also secondary end points.

At baseline, the median ages in the combination and placebo arms were 62 years and 61.5 years, respectively. Most patients in both arms had an ECOG performance status of 0 (56.4% versus 63.8%), visceral metastasis (71.3% versus 71.3%), and had received a prior CDK4/6 inhibitor for at least six months (86.2% versus 89.4%). Patients in both arms received prior adjuvant chemotherapy (28.7% versus 31.9%) and metastatic chemotherapy (12.8% versus 18.1%).

What were the additional efficacy and safety data seen with the combination?
At a data cutoff of May 26, 2025, updated OS data revealed that patients in the combination (105 patients) and placebo (107 patients) achieved a median OS of 29.5 months and 23.8 months, respectively.

In terms of safety, the most common any-grade side effects in the combination arm (92 patients) that occurred in at least 10% of patients were hyperglycemia (72.8%), diarrhea (51.1%), nausea (44.6%), decreased appetite (30.4%) and rash (30.4%). The most common any-grade side effects in the placebo arm (94 patients) were asthenia (16%), arthralgia (16%), increased alanine aminotransferase levels (14.9%), and increased gamma-glutamyl transferase levels (14.9%). Patients in the combination and placebo arms experienced any-grade side effects at respective rates of 100% and 86.2%; grade 3 or higher side effects occurred at rates of 70.7% and 33%, respectively.

“There were no new safety signals and the safety profile is in line with what we already know [about Piqray],” De Laurentiis said in his conclusion. “These data confirm and extend the SOALR-1 findings and support the use of Piqray plus Faslodex as an effective treatment option for patients with hormone receptor–positive, HER2-negative PIK3CA-mutated [breast cancer] after progression on CDK4/6 inhibitors.”

References

1. “Alpelisib plus fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor” by Dr. De Laurentiis, et al., San Antonio Breast Conference Symposium.
2. “FDA approves alpelisib for metastatic breast cancer.” FDA.

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