Background:

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved in Europe for the treatment of platinum-sensitive patients with newly diagnosed or recurrent platinum-sensitive ovarian cancer with a confirmed BRCA mutation or homologous recombination deficiency (HRD). Epidemiological studies have shown an incompatible association between ovarian cancer and obesity, but there have also been scientific reports indicating that obesity, especially severe obesity, increases the risk of ovarian cancer. Olaparib has a wide range of side effects, especially anaemia and neutropenia, which may lead to dose reduction or therapy discontinuation. Therefore, therapeutic drug monitoring (TDM) is recommended. The aim of the study was a retrospective analysis of threshold value of the trough concentration of olaparib (Ctrough) and haematological adverse reactions after olaparib treatment (300 mg/12 h) in excess-weight and normal body mass index (BMI) patients with ovarian cancer. Materials and

methods:

The pilot study was conducted on 38 ovarian cancer patients who were divided into two groups I - normal BMI patients (BMI = 18.5-24.9 kg/m2; n = 14), II - excess-weight patients, i.e. overweight and obese patients (BMI ≥ 25 kg/m2; n = 24). The severity of neutropenia and anaemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). The values of the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and red blood cell distribution width (RDW) parameters were also taken into account. HPLC-UV method (λ = 254 nm) was applied to measure olaparib plasma concentrations.

Results:

There were no statistically significant differences in olaparib Ctrough between the groups - 1602.86 vs. 1567.40 ng/mL (p = 0.9156). However, the overweight and obese patients had slightly higher dose/kg-adjusted olaparib Ctrough - 204.17 vs. 159.32 ng/mL/mg/kg. The incidence of grade 1 anaemia in the groups was as follows I - 42.86%, II - 41.67%. Grade 2 and 3 anaemia was observed only in group II - 4.17% and 8.33%, respectively. The incidence of neutropenia in the groups of patients was as follows grade 1 group I - 21.43%, group II - 20.83%; grade 2 group I - 7.14%, group II - 4.17%.

Conclusions:

The incidence of haematological adverse reactions to olaparib, such as neutropenia and grade 1 anaemia in the group of overweight and obese patients was the same as in the normal BMI group. The overweight and obese patients were characterised by higher severity of haematological adverse reactions to olaparib and slightly higher dose/kg-adjusted olaparib Ctrough. After one month of treatment with olaparib the overweight and obese patients had significantly lower red blood cells (RBC) and haemoglobin (Hgb) levels than the patients with normal BMI, which may indicate that anaemia develops faster in this group of patients.