Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1594 treated patients with ovarian cancer [see Adverse Reactions ( 6.1)] , MDS/AML occurred in 32 patients (2%), including those in long term follow-up. Of these, 14 occurred during treatment or during the 28-day safety follow-up (0.9%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from < 2 months to approximately 72 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing chemotherapy regimens and/or other DNA damaging agents.

In ARIEL3, of patients with a germline and/or somatic BRCAmutation treated with Rubraca, MDS/AML occurred in 9 out of 129 (7%) patients treated with Rubraca and 4 out of 66 (6%) patients treated with placebo. The duration of therapy with Rubraca in patients who developed secondary MDS/cancer therapy-related AML varied from 1.2 to 4.7 years.

In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation [see Adverse Reactions ( 6.1)].

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose according to Table 1[see Dosage and Administration ( 2.3)] and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.