A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.įemalesAdvise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.Įmbryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. Discontinue LYNPARZA if MDS/AML is confirmed. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery. Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. To understand the role of PARPis in the treatment of advanced ovarian cancerĢ.Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). In this session, we discuss the role of PARPis in the treatment of advanced ovarian cancer, with particular focus on the use of HRD testing to better define optimal therapy for front-line treatment of these patients.ġ. The HRD score has come to the fore as important individualised information in patients with advanced ovarian cancer, due to its correlation with response to maintenance PARPis in the first-line therapeutic setting.
Available tools have computed the following: loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions to derive a summated HRD score. The presence of HRD leads to detectable signature or genomic scar which can be scored by different tools. The lack of high-fidelity HRR in these cells leads to reliance on error-prone DNA repair pathways (e.g.: non-homologous end joining), further genomic instablity and cell death. PARPis are able to induce synthetic lethality in cells with HRD by binding to and trapping PARP1 and PARP2 to single-stranded DNA breaks, which generates double-stranded breaks. HRD results in irreparable DNA damage and increased sensitivity to platinum chemotherapy, as well as increased susceptibility to poly-ADP ribose polymerase (PARP) inhibitors. High grade serous ovarian cancer is characterized by genomic instability, with ~50% of advanced tumors harboring homologous recombination repair (HRR) pathway deficiency (HRD).