FDA Approves Roche’s Itovebi for Endocrine-Resistant, PIK3CA-Mutated Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

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The FDA has approved Roche’s Itovebi (inavolisib) in combination with Ibrance (palbociclib) and Faslodex (fulvestrant) for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer. The approval was based on data from the Phase III INAVO120 trial, which demonstrated that the Itovebi-based regimen significantly improved progression-free survival (PFS) compared to Ibrance and Faslodex alone. Investigators noted that 40% of all HR-positive metastatic breast cancers have the PIK3CA mutation.¹

“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target,” INAVO120 principal investigator Komal Jhaveri, MD, section head, endocrine therapy research portfolio, clinical director, early drug development service, Memorial Sloan Kettering Cancer Center, said in a press release. “The Itovebi-based regimen more than doubled progression-free survival and maintained a manageable safety and tolerability profile, adding a new standard in how PIK3CA-mutated breast cancers are treated.”

The randomized, double-blind, placebo-controlled INAVO120 trial evaluated the efficacy and safety of Itovebi in combination with Ibrance and Faslodex versus placebo plus Ibrance and Faslodex in patients whose disease progressed during treatment or within one year of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease. In the trial, 325 patients were randomly assigned to an investigational arm or a control arm. The primary endpoint of the study was PFS, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints included overall survival (OS), objective response rate, and clinical benefit rate.

Results found that the Itovebi-based regimen improved PFS by 15 months, while Ibrance and Faslodex alone only improved PFS by 7.3 months. Additionally, the combination therapy reduced the risk of disease progression or death by 57%. Currently, OS data are immature but demonstrating promise, according to investigators.

Serious adverse events (AEs) associated with Itovebi include difficulty breathing; blurred vision; nausea and vomiting; increased appetite; stomach pain; weight loss; excessive thirst; dry mouth; dry skin; dry mouth; confusion; sleepiness; mouth soars; and diarrhea. More common AEs include decreased white blood cell counts; COVID-19; headaches; increased blood levels of the liver enzyme alanine transaminase; and decreased blood levels of calcium, potassium, sodium, and magnesium.¹

“With the approval of this Itovebi-based regimen, we continue our long-standing track record of cancer therapeutic discovery by offering an important new first-line option for people living with HR-positive breast cancer with a PIK3CA mutation,” said Levi Garraway, MD, PhD, chief medical officer, head, global product development, Roche, in the press release. “Despite the high prevalence of PIK3CA mutations in this setting, treatment options have thus far remained limited, which makes today’s approval all the more significant.”

According to the National Cancer Institute, 70% of all breast cancers are HR-positive. Based on data from 2017 to 2021, there were around 90 new cases per 100,000 women, making it more than six times higher than the rate of HR-negative/HER2-negative breast cancer and HR-positive/HER2-positive breast cancer, while being around 17 times higher than HR-negative/HER2-positive breast cancer.²

“We are thrilled by the approval of the Itovebi-based regimen, which is a huge step forward for advanced breast cancer patients with a PIK3CA mutation,” said Jean Sachs, CEO, Living Beyond Breast Cancer, in the press release. “It remains critical that all patients have access to early, comprehensive biomarker testing so they can better understand what treatment options may be most beneficial for them and their tumor type.”

References

1. FDA Approves Genentech’s Itovebi, a Targeted Treatment for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer With a PIK3CA Mutation. Genentech. October 10, 2024. Accessed October 11, 2024. https://www.gene.com/media/press-releases/15039/2024-10-10/fda-approves-genentechs-itovebi-a-target

2. Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. Accessed October 11, 2024. https://seer.cancer.gov/statfacts/html/breast-subtypes.html