Bayer is targeting a broader use of Nubeqa in metastatic hormone-sensitive prostate (mHSPC) cancer with a combination free of chemotherapy.
Bayer plans to seek the FDA’s blessing for Nubeqa plus androgen deprivation therapy (ADT) in mHSPC after the phase 3 ARANOTE trial showed that the combination led to a statistically significant 46% reduction in the risk of progression or death compared with ADT alone.
The positive readout, shared at the European Society for Medical Oncology Congress 2024, complements an existing Nubeqa approval for use alongside ADT and the chemotherapy docetaxel in mHSPC. If approved, Nubeqa could cover the entire mHSPC population, Iris Kuss, M.D., Bayer’s global development lead for oncology, said in an interview with Fierce Pharma.
“Every patient is different,” Kuss said. “What we were missing was really the treatment for patients” who are not suitable for docetaxel.
Nubeqa’s radiological progression-free survival benefits were consistent in patients with high- and low-volume tumor burden, with risk reduction at 40% and 70%, respectively.
Data on whether the new Nubeqa chemo-free regimen can extend patients’ lives, a secondary endpoint of ARANOTE, remained immature. At the current data cutoff on June 7, the trial recorded a preliminarily positive trend in favor of Nubeqa toward a 19% reduction in the risk of death.
Back in 2022, Nubeqa’s combination with ADT and docetaxel was approved by the FDA in mHSPC based on results from the phase 3 ARASENS trial showing the chemo-containing regimen significantly cut the risk of death by 32% over ADT and docetaxel.
Overall survival data could take up to seven years to mature in mHSPC, Kuss noted. Bayer’s intention is to bring this chemo-free regimen to patients as quickly as possible so physicians can tailor treatment either with or without docetaxel, she added.
A relatively benign tolerability profile has been a selling point for Nubeqa in its competition with other earlier-to-market androgen receptor inhibitors such as Astellas and Pfizer’s Xtandi. In ARANOTE, treatment discontinuations due to treatment-emergent adverse events were somehow lower in the Nubeqa group at 6.1% versus 9% in the control group.
In another finding that Kuss called “puzzling,” patients in the Nubeqa arm also experienced a lower rate of fatigue, which is a common side effect of second-generation androgen receptor inhibitors. The rate of fatigue was 5.6% and 8.1% for Nubeqa and the comparator, respectively.
Nubeqa looks well on track to cross the blockbuster threshold this year with sales in the first six months of 2024 reaching 663 million euros ($735 million), good for 75% growth year over year.
Elsewhere in mHSPC, Novartis is trying to pair its radioligand therapy Pluvicto with ADT and androgen receptor-directed therapy like Nubeqa in the phase 3 PSMAddition trial. That study is expecting a readout in 2025.
Meanwhile, Bayer is further evaluating Nubeqa in nonmetastatic hormone-sensitive prostate cancer in the phase 3 ARASTEP trial. Xtandi already reached that earlier treatment setting thanks to an FDA approval in November.