Editor’s note: Hormone receptor-positive (HR+) breast cancer is the most common subtype of breast cancer, with approximately 40% of these patients harboring a PI3KCA mutation. This mutation is a primary cause of resistance to endocrine therapy and CDK4/6 inhibitors, leading to poorer prognosis for affected patients. At the 2024 CSCO Annual Meeting, Dr. Jiong Wu from Fudan University Shanghai Cancer Center, as the Leading PI, shared the latest findings from the Phase III INAVO120 study. The study demonstrated that the novel PI3K inhibitor, inavolisib, combined with CDK4/6 inhibitors and endocrine therapy, offers improved outcomes for these patients, providing a new treatment option. Based on these results, both the China National Medical Products Administration (CDE) and the U.S. FDA have granted fast-track review status to inavolisib, with hopes of delivering clinical benefits to patients soon. At the CSCO meeting, Oncology Frontier had the opportunity to interview Professor Wu, discussing key insights about inavolisib and providing clinical guidance on this emerging PI3K inhibitor.

01 Oncology Frontier: Based on the results of the INAVO120 study, the CDE granted inavolisib breakthrough therapy and fast-track approval earlier than the FDA. As the Leading PI of this study, how do you feel about the accelerated approval process of this drug?

Dr. Jiong Wu: The INAVO120 study offers a new and highly effective treatment strategy for HR+/HER2- advanced breast cancer patients with PI3KCA mutations. It involves using the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant as a first-line treatment regimen.

Patients with PI3KCA mutations typically have a poor prognosis and are more likely to develop resistance to current endocrine therapies and CDK4/6 inhibitors, increasing the risks of disease progression and overall mortality. Importantly, about 40% of HR+/HER2- breast cancer patients carry this mutation, and the mutation rate is even higher in Chinese patients. PI3KCA mutations activate the PAM (PI3K/AKT/mTOR) pathway, which promotes tumor cell proliferation, invasion, and metastasis. Therefore, targeting this pathway with precise therapies will provide better outcomes for these patients.

02 Oncology Frontier: As inavolisib, a targeted therapy for PI3KCA-mutated HR+/HER2- breast cancer, approaches market approval, what are your expectations for its clinical application?

Dr. Jiong Wu: Inavolisib has wide clinical potential. We know that the HR+ subtype accounts for about 70% of all breast cancers, meaning the patient base is large. While HR+ patients generally have better prognoses, the risk of recurrence is prolonged, with some patients experiencing disease progression even 15 years after treatment.

Currently, patients with PI3KCA mutations develop resistance to first-line treatments more quickly, and both clinicians and patients are eager for more effective and precise therapeutic options. While one PI3K inhibitor is already available on the market, its adverse effects necessitate careful management in clinical settings. Therefore, the development of stronger and safer targeted therapies is an inevitable trend. In the INAVO120 study, the combination of inavolisib with palbociclib and fulvestrant showed significant clinical efficacy, with a marked improvement in median progression-free survival (mPFS) compared to the control group (15.0 months vs. 7.3 months, HR=0.43, P<0.0001), giving patients more hope.

03 Oncology Frontier: Inavolisib propels HR+/HER2- breast cancer treatment into the era of precision targeted therapy, emphasizing the importance of “precision treatment guided by early diagnosis.” When do you think is the optimal time for conducting PI3KCA testing?

Dr. Jiong Wu: In recurrent or metastatic breast cancer, selecting a treatment plan for a specific target relies on genetic testing. This includes testing for PI3KCA and other mutations to ensure a more accurate classification of treatment. Breast cancer treatment has evolved from traditional “classified therapy” to the “precision-classified therapy” era. Early genetic testing can identify patients’ mutation characteristics, helping to predict potential resistance and guiding appropriate treatments.

Regarding PI3KCA testing, various domestic and international guidelines, including the Consensus on the Clinical Application of PI3K/AKT/mTOR Pathway Inhibitors for Breast Cancer Treatment, recommend testing when a patient first experiences recurrence. This can be done using either tumor tissue samples or circulating tumor DNA from blood samples. Such testing helps clinicians identify key driver genes in the PAM pathway, enabling them to select optimal patients for treatment and make more precise therapeutic decisions.

Dr. Jiong Wu

Dr. Jiong Wu is the Executive Vice President of Fudan University Shanghai Cancer Center, Chief Physician, and PhD Supervisor. He also serves as the Director of the Drug Clinical Trial Institution, Chairman of the Breast Cancer Committee of the Chinese Anti-Cancer Association, and Vice Chairman of the Breast Surgery Committee of the Chinese Medical Doctor Association. He is a standing committee member of the Chinese Society of Clinical Oncology (CSCO) and Deputy Chair of the Shanghai Anti-Cancer Association Breast Cancer Committee.