Inavolisib Regimen Continues to Improve Survival in PIK3CA-Mutated Breast Cancer

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Inavolisib (Itovebi) plus fulvestrant and palbociclib (Ibrance) led to a statistically significant and clinically meaningful benefit in progression-free survival (PFS) vs fulvestrant and palbociclib alone in patients with hormone receptor-positive (HR+), HER2-negative (HER2–), PIK3CA-mutated breast cancer, according to the latest data from the phase 3 INAVO120 study (NCT04191499) published in The New England Journal of Medicine.¹

The inavolisib regimen reduced the risk of disease progression or death by 57% compared with palbociclib alone, with PFS of 15.0 months vs 7.3 months, respectively (HR, 0.43; 95% CI, 0.32-0.59; P <.001). The PFS benefit was observed across all prespecified subgroups, including in patients with disease that had spread to 3 or more sites.

Overall survival (OS) data were immature at the time of this analysis but demonstrated a positive trend with a stratified HR of 0.64 (95% CI, 0.43-0.97; P =.03).

“With a doubling of progression-free survival and consistent benefits in [patients] whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients,” said Komal Jhaveri, MD, section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and a principal investigators of the INAVO120 study, in a press release. “I’m confident this [inavolisib]-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis.”

On October 10, 2024, the FDA approved the inavolisib regimen patients with HR+, HER2–, locally advanced or metastatic breast cancer following recurrence on or after completing adjuvant endocrine therapy. The approval was supported by data from INAVO120.²

Data from INAVO120 were also presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. In the ASCO results, the time from randomization to end of next-line treatment was 24.0 months with the addition of inavolisib vs 15.1 months for palbociclib and fulvestrant alone (HR, 0.54; 95% CI, 0.38-0.77). The time to first chemotherapy was not yet reached with the addition of inavolisib compared with 15.0 months with placebo (unstratified HR, 0.54; 95% CI, 0.37-0.78).³

The INAVO121 (NCT05646862) and INAVO122 (NCT05894239) trials are also evaluating different inavolisib combinations for the treatment of patients with PIK3CA-mutated breast cancer.¹

REFERENCES:

1. New England Journal of Medicine publishes landmark phase III results for Roche’s Itovebi, showing more than doubling of progression-free survival in certain type of HR-positive advanced breast cancer. News release. Roche. October 31, 2024. Accessed October 31, 2024. https://tinyurl.com/t8jw8zbm

2. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. News release. FDA. October 10, 2024. Accessed October 31, 2024. https://tinyurl.com/ynkka5ta

3. Juric D, Kalinsky K, Turner N, et al. First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2‑negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses. J Clin Oncol. 2024;42 (suppl 16):1003. doi:10.1200/JCO.2024.42.16_suppl.1003.