Dr Winer on Considerations for Inavolisib Plus Palbociclib and Fulvestrant in PIK3CA-Mutated HR+/HER2– Breast Cancer

"This is not a treatment for a patient with limited bone involvement with a very low volume of disease…or for somebody who has an up-front presentation. It's [for] a population of patients where you're really worried about the impact that hormonal therapy will have. You want to take advantage of every bit of extra help you can [get] to ensure that the patient is going to do well for as long as possible on that treatment."

Eric Winer, MD, director, Yale Cancer Center; president, physician-in-chief, Smilow Cancer Hospital, discusses crucial considerations for the use of inavolisib (Itovebi) plus palbociclib (Ibrance) with fulvestrant (Faslodex) in the advanced setting for select patients with hormone receptor (HR)–positive, HER2-negative breast cancer, following the FDA approval of this regimen in October 2024.

During an FDA special session moderated by Winer at the 2024 San Antonio Breast Cancer Symposium (SABCS), discussion centered on the FDA approval process, including key factors considered when defining the appropriate patient population for new agents.

For inavolisib, the consensus was that this regimen should be reserved for patients who develop metastatic disease while on endocrine therapy or within 1 year of completing adjuvant endocrine therapy, Winer reports. Importantly, the combination is not intended for those presenting with de novo stage IV disease, he notes. The study population primarily consisted of patients with visceral metastases, indicating that this approach is best suited for individuals with a more aggressive disease course where additional intervention beyond hormonal therapy is warranted, he says.

Conversely, patients with limited bone involvement or low-volume disease, even in visceral sites, may not be ideal candidates for this regimen, Winer continues. The rationale is to maximize treatment benefit in those at higher risk of rapid disease progression, ensuring prolonged disease control with the most effective first-line approach, he explains. These considerations underscore the need for careful patient selection when integrating novel targeted agents into clinical practice, Winer concludes.