Dr Rugo on the Safety Profile of Alpelisib in PI3K-Mutant HR+/HER2– Advanced Breast Cancer

“The alpelisib toxicity [profile] wasn’t well addressed in SOLAR-1, and we were surprised by the toxicities. We tried to give an idea of when the toxicities occurred and how to manage them; however, it’s tough and [this realization was] quite a bit after people started using the drug and felt burned by the toxicity.”

Hope S. Rugo, MD, a professor in the Department of Medical Oncology and Therapeutics Research, division chief of Breast Medical Oncology, and the director of the Women’s Cancers Program at the City of Hope, detailed the safety profile of alpelisib (Piqray) for the treatment of patients with PI3K-mutant hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

In the SOLAR-1 trial (NCT02437318), the toxicity profile of alpelisib was not initially well addressed, which led to unexpected toxicities among patients treated with the PI3K inhibitor, Rugo began. Following data from the study that led to the May 2019 FDA approval of alpelisib for the treatment of patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer, she noted that the investigators followed up with details on when toxicities occurred and how to manage them. However, this happened after it had been used in clinical practice, and some of the main toxicities were difficult to manage, namely hyperglycemia, she explained. At the time of the FDA approval of alpelisib, the current oral hypoglycemic drugs were not available, which are now known to be effective and well tolerated, with some cases of nausea, Rugo concluded.

In the final overall survival results from SOLAR-1, published in 2021, safety data revealed that the incidence of hyperglycemia did not increase with longer time on treatment. Of note, the most frequent adverse effects that occurred in at least 20% of patients in the alpelisib plus fulvestrant (Faslodex) arm (n = 284) included hyperglycemia (any grade, 64.8%; grade 3, 33.1%; grade 4, 3.9%), diarrhea (any grade, 59.5%; grade 3, 7.0%), nausea (46.8%; 2.8%), decreased appetite (36.3%; 0.7%), rash (36.3%; 9.9%), vomiting (28.5%; 0.7%), decreased weight (27.8%; 5.3%), fatigue (25.4%; 3.5%), stomatitis (25.0%; 2.5%), asthenia (22.5%; 2.5%), and alopecia (any grade, 20.4%).