ESMO: Bayer aims to widen Nubeqa's prostate cancer use with chemo-free treatment

Bayer's Nubeqa is on a successful trajectory in 2024, with sales reaching 663 million euros ($735 million) in the first half of the year. This positions Nubeqa to potentially achieve blockbuster status by the end of the year. The drug is currently being explored for broader use in treating metastatic hormone-sensitive prostate cancer (mHSPC) through a chemotherapy-free combination treatment.

Bayer aims to secure FDA approval for a combination of Nubeqa and androgen deprivation therapy (ADT) for mHSPC, following promising results from the phase 3 ARANOTE trial. The trial demonstrated that the combination significantly reduced the risk of progression or death by 46% compared to ADT alone. These findings, shared at the European Society for Medical Oncology Congress 2024, could potentially extend Nubeqa's current approval, which includes its use alongside ADT and chemotherapy drug docetaxel in mHSPC. Iris Kuss, M.D., Bayer’s global development lead for oncology, highlighted the importance of this expansion, particularly for patients who are unsuitable for chemotherapy like docetaxel.

The ARANOTE trial's data showed consistent radiological progression-free survival benefits for Nubeqa, reducing risk by 40% and 70% for patients with high- and low-volume tumor burden, respectively. However, data on the chemo-free regimen's impact on overall survival—a secondary endpoint of the trial—remains immature. As of the cutoff date on June 7, the trial indicated a positive trend towards a 19% reduction in the risk of death favoring Nubeqa.

Previously, in 2022, the FDA approved the combination of Nubeqa with ADT and docetaxel for mHSPC based on phase 3 ARASENS trial results. This approval was granted after the chemo-inclusive regimen showed a 32% reduction in the risk of death over ADT and docetaxel alone. Kuss emphasized Bayer's commitment to providing a chemo-free regimen option to patients, allowing physicians to tailor treatments more effectively, whether or not they include docetaxel.

Nubeqa’s relatively benign tolerability profile has been a competitive advantage over other androgen receptor inhibitors like Astellas and Pfizer’s Xtandi. In the ARANOTE trial, treatment discontinuations due to adverse events were lower in the Nubeqa group (6.1%) compared to the control group (9%). Additionally, the Nubeqa arm experienced a lower rate of fatigue, a common side effect of second-generation androgen receptor inhibitors, with 5.6% of patients reporting fatigue compared to 8.1% in the comparator group.

Looking forward, Novartis is also exploring treatment combinations in mHSPC. The company is testing its radioligand therapy Pluvicto with ADT and androgen receptor-directed therapies, like Nubeqa, in the phase 3 PSMAddition trial, with results expected in 2025. Bayer, meanwhile, continues its research on Nubeqa, investigating its potential use in nonmetastatic hormone-sensitive prostate cancer through the phase 3 ARASTEP trial. In this earlier treatment setting, Xtandi has already secured FDA approval as of November.