Inavolisib for HR-Positive, HER2-Negative Advanced Breast Cancer: Clinical Trials and Patient Access Implication.

Objectives: Breast cancer remains the most prevalent cancer among women in the United States, with hormone receptor-positive (HR+) and HER2-negative subtypes comprising a significant proportion of cases. Despite advancements in treatment, resistance to endocrine therapies remains a substantial clinical challenge, especially in patients with mutations in the PIK3CA gene.

Methods: A literature review was conducted to evaluate the safety and efficacy of inavolisib in breast cancer. Studies published through November 2024 were identified using PubMed, Google Scholar, and ClinicalTrials.gov. Phases I to III clinical trials in English were included. The review focused on safety outcomes (eg, serious adverse events) and efficacy outcomes (eg, progression-free survival), which were summarized narratively.

Results: Inavolisib, a selective PI3Kα inhibitor, presents a promising option for patients with PIK3CA-mutated HR+HER2-negative advanced or metastatic breast cancer. In the INAVO120 trial, inavolisib combined with palbociclib and fulvestrant significantly extended progression-free survival (PFS) in patients with PIK3CA mutations. The median PFS was 15.0 months for the treatment arm compared with 7.3 months in the placebo group (hazard ratio: 0.43, P<0.001). The objective response rate (ORR) was 58.4% in the treatment arm, underscoring the drug's antitumor efficacy. Safety profiles revealed manageable adverse events, primarily hyperglycemia, neutropenia, and stomatitis. The incidence of these side effects was notable but manageable with appropriate supportive care. Inavolisib offers a new treatment for HR+HER2-negative advanced breast cancer, showing promising efficacy and safety. However, implementation challenges include high costs, insurance coverage issues, and limited access to required genetic testing through FoundationOne Liquid CDx assay, potentially creating barriers to equitable patient access.

Conclusions: Inavolisib represents a significant advancement in the treatment of advanced HR+HER2-negative breast cancer, offering an effective option for patients with PIK3CA mutations. However, to fully realize its potential, health care systems must address challenges related to patient access, insurance coverage, and the availability of companion diagnostics. Further long-term studies will be essential to assess the enduring impact of this treatment on patient outcomes.