Breast Cancer, New Drug Mix for Advanced Forms

Among advanced or metastatic breast cancers, some forms are more aggressive than others. Hormone-sensitive breast cancers (Hr+/Her2-) have seen a significant increase in survival in recent years, but among these there are some that are more difficult to treat: those with the Pik3ca mutation, which account for approximately 40%. One of the latest positive pieces of news from the annual meeting of the American Society of Clinical Oncology (Asco) concerns precisely these forms: a mix of three drugs has in fact allowed patients' survival to be significantly increased. The data were published simultaneously in the New England Journal of Medicine .

The study

The study (Inavo120) was conducted on 325 patients and tested a new oral drug directed against Pik3ca mutations, inavolisib, in combination with palbociclib and fulvestrant (a standard of first-line care for advanced cancer). The enrolled patients had progressed during treatment or within 12 months of completing adjuvant endocrine therapy, and had not received previous systemic therapy for metastatic disease. Half of them were randomly assigned to receive standard therapy plus inavolisib.

The results

The new results just presented concern the median overall survival: it was 34 for patients in the inavolisib arm compared to 27 months in the palbociclib and fulvestrant-only arm, with a 30% reduction in the risk of death. The benefit already observed in delaying tumor progression was also maintained: it was 17.2 months compared to 7.3 months, with a delay in the use of chemotherapy of about two years.

The inavolisib-based regimen also demonstrated a statistically significant improvement in the percentage of patients whose cancer completely disappeared or significantly reduced after treatment (objective response rate). Finally, no new safety risks were observed, confirming its tolerability.

"These important data for the inavolisib-containing regimen have shown not only a doubling of progression-free survival, but more importantly that the combination is able to prolong life and delay the time to chemotherapy," said Nicholas Turner , lead author of the study, professor of Molecular Oncology at the Institute of Cancer Research in London. "These results suggest that this regimen could become the new standard of care in the first line, as it has demonstrated a substantial benefit on patients' clinical outcomes and their quality of life."

What is inavolisib

Inavolisib belongs to the class of PI3K inhibitors, but has a unique mechanism of action and a high specificity for Pik3ca mutations that facilitate the degradation of the “wrong” protein. Currently, the inavolisib-based regimen is approved in several countries, including the United States and last May it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the EMA: the final decision on approval by the European Commission is now awaited. The drug is currently being tested in other studies in the context of locally advanced or metastatic breast cancer with Pik3ca mutation in various combinations, including in Her2-positive disease.