Expanded drug indications for breast and prostate cancer

Medicines

20 Mar 2025

Two targeted therapies have become available to reduce the risk of recurrence in Australian patients with breast cancer and to delay disease progression in non-metastatic hormone-sensitive prostate cancer with biochemical recurrence.

Ribociclib in early breast cancer

The CDK4/6 inhibitor ribociclib (Kisqali, Novartis Australia) has now been TGA registered, in combination with a non-steroidal aromatase inhibitor (NSAI), for the adjuvant treatment of patients with HR+/HER2- stage II and III early breast cancer at high risk of recurrence including those with high-risk node-negative disease.

Ribociclib has previously only been available for the management of patients with HR+/HER2- advanced or metastatic breast cancer.

The TGA registration for ribociclib in early breast cancer is underpinned by results from NATALEE clinical trial, previously reported in the limbic [link here].

An interim analysis of the study found three years of treatment with ribociclib plus a NSAI, compared with a NSAI alone, significantly improved invasive disease–free survival among patients with HR+/HER2- stage II or III early breast cancer including node-negative or node-positive disease.

More recent four-year trial data from NATALEE was presented at the ESMO Congress in September 2024, demonstrating that ribociclib combined with a NSAI, reduced the risk of breast cancer recurrence by 28.5% compared to a NSAI alone.

“Based on the NATALEE trial results, the NCCN Guidelines were recently updated to recommend Kisqali®, in combination with an AI, as a Category 1 preferred CDK4/6 inhibitor for adjuvant treatment of patients with HR+/HER2- EBC, including those with high-risk, node-negative disease,” a statement from Novartis said.

Enzalutamide in prostate cancer

Meanwhile, the androgen receptor signalling inhibitor enzalutamide (Xtandi, Astellas Australia) is now available for patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with biochemical recurrence at high-risk for metastasis.

The expanded indication, which provides earlier access to enzalutamide for Australian men, is based on results from the phase 3 EMBARK trial.

The trial, published in the NEJM in 2023 [link here], found that enzalutamide, both in combination with leuprolide and as monotherapy, significantly improved metastasis-free survival in men with high-risk biochemical recurrence of prostate cancer, compared to leuprolide alone.

High-risk biochemical recurrence was defined as a PSA doubling time of ≤9 months.

It found that at 5 years, metastasis-free survival was 87.3% in the enzalutamide plus leuprolide group, 80.0% in the enzalutamide monotherapy group and 71.4% in the leuprolide alone group.

“The risk of metastasis or death was 57.6% lower in the combination group than in the leuprolide-alone group, a difference that was significant (hazard ratio, 0.42; 95% CI, 0.30 to 0.61; P<0.001),” the study said.

Treatment with enzalutamide in combination or as monotherapy also resulted in a longer time to distant metastasis, symptomatic progression, and first symptomatic skeletal event.

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