Regulatory Decision Summary for Ibrance

Because of the rarity of male breast cancer (BC), randomized clinical studies in this patient population are not feasible. A review of Pfizer global safety database suggests that the adverse events (AEs) observed in male patients with advanced BC treated with palbociclib was consistent with the known tolerable and manageable AE profile of palbociclib, with no new safety signals identified. In addition, Phase 1 studies conducted with male patients administered single dose palbociclib showed no substantial gender differences in the frequency or severity of AEs. The population pharmacokinetic analysis of palbociclib further indicated no effect of gender on the pharmacokinetics of palbociclib. Thus, palbociclib at the intended dose level can be considered to have an acceptable safety profile for the treatment of male patients with advanced BC. While real-world effectiveness data from retrospective cohort studies utilising electronic health care claims information and Electronic Health Records also suggested a benefit of palbociclib treatment of men with BC, no definitive conclusions could be drawn due to the exploratory nature of the analysis. However, based on the mechanism of action of palbociclib and the similar clinical features of BC between males and females, no biologically plausible gender difference in either efficacy or safety among patients treated with Ibrance is expected. The submitted Real World Evidence provided further assurance for the use of Ibrance in combination with endocrine therapy for the treatment of male BC, thereby aligning with the currently approved indications in women.

The updated efficacy results from pivotal study 1008 with an additional 15 months of follow-up verified the clinical benefit of palbociclib in combination with letrozole for the treatment of post-menopausal women with ER-positive and HER2- negative advanced or metastatic BC. The Clinical Trials section of the Ibrance PM is updated to describe relevant clinical trial results.

Non-clinical studies showed a significantly greater increase in the incidence of malignant microglial cell tumors in the central nervous system of male rats compared with controls; however, the relevance of these findings to humans is unknown. The text included in the Warnings and Precautions section of the Ibrance PM serves as an appropriate risk-mitigation measure.

Overall, extrapolation of the previously approved indications of Ibrance for the treatment of women with advanced BC to men based on the totality of the available data is considered reasonable and acceptable. Uncertainties associated with expanding the indication to men based on Real World Evidence are outweighed by the observed consistent safety and pharmacokinetic profiles between genders, the biological plausibility for extrapolation, and the rare nature of the disease for which there are limited treatment options. Additional revisions to the Ibrance PM are appropriate, with the benefit/harm/uncertainty remaining positive for all approved indications.