Regulatory Decision Summary for Nubeqa

Clinical efficacy and safety for the proposed indication were supported primarily by a randomized, double-blind, placebo-controlled, multi-centre trial that evaluated Nubeqa in combination with docetaxel in 1306 patients with mCSPC. Patients must have been candidates for docetaxel therapy per investigator judgement, and all patients must have started androgen-deprivation therapy (ADT).

A statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS) was observed in the Nubeqa plus docetaxel arm, with a 32.5% reduction in the risk of death compared with the placebo plus docetaxel arm. The median OS was not reached in the Nubeqa plus docetaxel arm and was 48.9 months in the placebo plus docetaxel arm.

The secondary endpoints of time to castration-resistant prostate cancer, time to pain progression, symptomatic skeletal event-free survival, time to first symptomatic skeletal event, and time to initiation of subsequent systemic antineoplastic therapy all showed a statistically significant advantage for Nubeqa plus docetaxel compared with placebo plus docetaxel, although these endpoints were associated with limitations such as timing of radiographic assessments, confounding by subsequent therapy, and/or investigator subjectivity.

As patients received Nubeqa in combination with docetaxel, the adverse event profile in metastatic castration-sensitive prostate cancer differed from the previously established profile of Nubeqa as monotherapy in non-metastatic castration-resistant prostate cancer. In the current mCSPC study, the most common adverse drug reactions (≥20% in either arm) were alopecia, fatigue, anemia, arthralgia, peripheral edema, neutrophil count decreased, diarrhea, white blood cell count decreased, and constipation. Adverse drug reactions reported at a ≥10% incidence and a ≥2% higher incidence in the Nubeqa plus docetaxel arm than in the placebo plus docetaxel arm were hypertension, constipation, decreased appetite, weight increased, pain in extremity, hemorrhage, and rash.

Significant new safety risks for Nubeqa included hepatic transaminase elevations and seizures, both of which were added to the Warnings and Precautions section of the Nubeqa Product Monograph, as well as hemorrhage, which was described in the Adverse Reactions section. Additionally, the previously identified risk of ischemic heart disease was confirmed in the present study, and a cardiovascular warning was added to the Warnings and Precautions section. The primary tool for risk mitigation is the Nubeqa Product Monograph.

A Risk Management Plan (RMP) for Nubeqa was submitted by Bayer Inc. to Health Canada. The RMP, designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimise risks associated with the product, was considered acceptable upon review.

Overall, treatment with Nubeqa plus docetaxel in patients with mCSPC demonstrated significant improvement in overall survival over docetaxel alone, and was associated with a manageable safety profile. Therefore, the benefit-risk is considered positive under the proposed conditions of use.