Talzenna Adverse Reactions

Summary of the safety profile: The overall safety profile of Talzenna is based on pooled data from 1 088 patients, including 690 patients who received talazoparib monotherapy at 1 mg daily in clinical studies for solid tumours and 398 patients with mCRPC who received talazoparib 0.5 mg in combination with enzalutamide 160 mg in the TALAPRO-2 study.
The most common (≥20%) adverse reactions in patients receiving talazoparib in these clinical studies were anaemia (55.6%), fatigue (52.5%), nausea (35.8%), neutropenia (30.3%), thrombocytopenia (25.2%) and decreased appetite (21.1%). The most common (≥10%) Grade ≥3 adverse reactions of talazoparib were anaemia (39.2%), neutropenia (17.4%), and thrombocytopenia (11.1%).
Dose modifications (dose reductions or dose interruptions) due to any adverse reaction occurred in 58.7% of patients receiving Talzenna 1 mg monotherapy. The most common adverse reactions leading to dose modifications were anaemia (33.5%), neutropenia (11.7%), and thrombocytopenia (9.9%). Permanent discontinuation due to an adverse reaction occurred in 2.9% of patients receiving Talzenna; the most common was anaemia (0.6%). The median duration of exposure was 5.6 months (range 0.0 to 70.2).
Dose interruptions of Talzenna due to adverse reactions occurred in 62.1% of patients with mCRPC receiving Talzenna in combination with enzalutamide; the most common was anaemia(44%). Dose reductions of Talzenna due to adverse reactions occurred in 52.8% of patients; the most common was anaemia (43.2%). Permanent discontinuation of Talzenna due to adverse reactions occurred in 18.8% of patients; the most common was anaemia (8.3%). The median duration of talazoparib exposure was 86 weeks (range 0.29 to 186.14).
Tabulated list of adverse reactions: Table 5 summarises adverse reactions based on pooled dataset listed by system organ class, and frequency category. Frequency categories are defined as: very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥ 1/1 000 to < 1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 5.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Myelosuppression: Myelosuppression-related adverse reactions of anaemia, neutropenia, and thrombocytopenia were very commonly reported in patients treated with talazoparib. Grade 3 and Grade 4 myelosuppression-related events were reported for anaemia 37.8% and 1.5% of patients, neutropenia 15.0% and 1.6%, and thrombocytopenia 8.1% and 3.0%. No deaths were reported due to myelosuppression-related adverse reactions.
In monotherapy studies (1 mg/day population), the most frequent myelosuppression-related adverse events associated with dose modifications were anaemia (33.5%), neutropenia (11.7%) and thrombocytopenia (9.9%) reported for up to approximately 30% of patients in the talazoparib 1 mg/day population and the one associated with permanent study drug discontinuation was anaemia reported in 0.6% of patients.
In patients with mCRPC treated with talazoparib in combination with enzalutamide, anaemia led to talazoparib dose interruption in 44.0% of patients, decreased neutrophil count in 13.6%, and decreased platelet count in 7.8%. Overall, 42.5% of patients required blood transfusions. The most common blood transfusion was of packed red blood cells 39.2%. Discontinuation due to anaemia, neutropenia and thrombocytopenia occurred, respectively, in 8.3%, 3.3% and 0.5% of patients.