As per Delveinsight’s estimates, there are approximately 200,000 HR+/HER2- Breast cancer patients, and 40% harbor PI3KCA mutation. Effective treatments for patients with PIK3CA-mutated, HR+HER2-advanced breast cancer are urgently needed. Preclinical studies have highlighted the significant synergy achieved through simultaneous inhibition of the PI3K, CDK4/6, and estrogen receptor pathways, offering promise in enhancing responses and overcoming resistance. Inavolisib, a potent and selective inhibitor targeting the catalytic alpha isoform subunit of the PI3K complex, presents a compelling option. Its ability to promote the degradation of mutated p110 alpha underscores its potential to address the specific needs of this patient subgroup. With mutation-specific therapies such as LYNPARZA, PIQRAY, and ORSERDU, where ORSERDU is gaining strong momentum since its approval in ESR1 mutated HR+/HER2- Breast cancer. However, PIQRAY is the first and only PI3K inhibitor approved, and now, new players like Roche targeting the same patient pool signal a pivotal opportunity for advancing treatment options. Pending approval, Inavolisib holds promise for improving outcomes in PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer patients.

Efficacy endpoints included time from randomization to the end of next-line treatment (a proxy for PFS2) and the first chemotherapy (TTFC). Key events adverse were reported. The results presented at ASCO 2024 were as follows:

Efficacy outcomes 

• INAVO120 met its primary endpoint, with a statistically significant and clinically meaningful improvement in PFS (15.0 months versus 7.3 months)

• OS was not met as the prespecified analysis

• PFS2 was 24 vs 15.1 months

Safety overview:

• Key adverse events were mostly Grade 2 and had resolved 

• Key adverse events are hyperglycemia, diarrhea, rash, and stomatitis.

• Manageable safety and tolerability profile

KOL insights

“Update on the INAV0120 study was also presented, which evaluated the addition of inavolisib to palbociclib and fulvestrant with an increase in progression-free survival of patients with HR+ HER2- metastatic.” –Expert Opinion.

“Inavolisib combo with palbociclib and fulvestrant showed significant improvement in PFS (15.0 vs 7.3 months), supporting its potential as a promising treatment option for HR+, HER2-LA/mBC—manageable safety profile and improved”–Expert Opinion.

Conclusion-

The combination of Inavolisib with palbociclib and fulvestrant showcased sustained benefits extending beyond disease progression, leading to postponed chemotherapy administration while maintaining manageable safety and tolerability. Notable increases in median "PFS2" and time to first chemotherapy (TTFC) were observed in the Inavolisib arm compared to placebo, with key adverse events mostly manageable at Grade 2 and resolving over time. Inavolisib-treated patients experienced longer periods without worsening pain severity and sustained day-to-day functioning and health-related quality of life. Importantly, the treatment did not contribute to additional burden according to patient-reported outcomes, suggesting its potential as a new standard of care in this setting.