Regulatory Decision Summary for Talzenna

The Sponsor provided a pivotal, multinational, multicenter, open-label, randomized, parallel, phase III study of Talzenna (talazoparib tosylate) compared to a physicians choice of chemotherapy (PCT) in adult patients with germline breast cancer susceptibility gene (BRCA)-mutated, human epidermal growth factor receptor 2 (HER2) negative, locally advanced (laBC) or metastatic breast cancer (mBC).

Talzenna treatment demonstrated a clinically meaningful and statistically significant improvement in progression free survival (PFS) as compared to the PCT arm (8.6 months versus 5.6 months) (hazard ratio [HR]: 0.54; 95% CI: 0.41, 0.71; p-value <0.0001) as determined by blinded independent central review (BICR). Additionally, the PFS was supported by the BICR assessed subgroup analyses, investigator assessed sensitivity analyses, as well as the achievement of confirmed objective response rates of 50% versus 18% favouring the Talzenna arm as compared to the PCT arm. Overall survival data were immature, but suggested no overt detriment to patients on the Talzenna arm.

The safety profile of Talzenna has been characterized based on the pivotal and supportive clinical studies involving 494 patients with germline BRCA mutated HER2 negative, laBC or mBC. The identified significant safety risks are hematologic toxicity, embryofetal toxicity and secondary primary malignancies. Other important toxicities include hepatotoxicity and gastrointestinal toxicity. These toxicities, although significant, were consistent between the pivotal and supportive studies, clearly highlighted in the Adverse Reactions table and the Warnings and Precautions section of the Product Monograph (PM), and generally manageable, as demonstrated in the pivotal trial, by dose interruption, dose reduction, dose discontinuation and/or standard medical practice. These mitigation strategies are clearly outlined in the PM. Additionally, a Serious Warnings and Precautions Box has been added to the PM to highlight the more severe, fatal and or life-threatening safety risks including embryofetal toxicity and the secondary primary malignancy of myelodysplastic syndromes/acute myeloid leukemia.

In summary, the study met its primary endpoint demonstrating a superior PFS benefit favouring Talzenna as compared to PCT. This efficacy was coupled with an acceptable and manageable safety profile. Therefore, the benefit risk is considered positive under the proposed conditions of use.