Germline PALB2-mutated triple negative breast cancer treated with Olaparib in a kidney transplant patient

Olaparib, a poly(ADP-ribose) polymerase inhibitor, is a commonly used agent in the treatment of human epidermal growth factor receptor 2–negative metastatic breast cancer carrying germline BRCA1/2 pathogenic variants. Phase II evidence has demonstrated antitumor activity in patients with partner and localizer of BRCA2 (PALB2) mutations. Olaparib is typically dosed at 300 mg twice daily with dose reduction required for creatinine clearance (CrCl) of 31–50 mL/min. Pharmacokinetic and dosing data remain insufficient for patients with severe kidney impairment (CrCl <30 mL/min) or kidney failure. Dose reductions are also required when olaparib is coadministered with strong or moderate CYP3A inhibitors. We describe a 47-year-old woman with recurrent metastatic triple-negative breast cancer and a failing deceased-donor kidney allograft. Multigene testing identified a germline pathogenic PALB2 c.388del variant. She received an empirical olaparib starting dose of 150 mg twice daily because of severe kidney impairment (CrCl 13 mL/min) and uncertainty concerning concomitant tacrolimus use. During olaparib treatment, she developed fatigue, anorexia, and grade 3 anemia requiring transfusions. Anemia prompted a six-week treatment interruption followed by individualized dose re-escalation. Her best response was a RECIST partial response, with a progression-free interval of eight months despite substantial hematologic toxicity. This observation cannot establish safety or an optimal dose in patients with severe kidney impairment; further pharmacokinetic and prospective clinical evidence is needed.