A Novel Adverse Event Associated with Olaparib Therapy in a Patient with Metastatic Breast Cancer

Abstract

Olaparib was first FDA approved for use in women with advanced ovarian cancer and germline BRCA mutations. Based on the results of subsequent research, the use of this drug has been expanded to patients with metastatic breast cancer with germline BRCA mutation. With the use of a relatively new medication and a larger patient population eligible for therapy, monitoring for novel adverse events associated with therapy is important. This case represents a patient with metastatic breast cancer and germline BRCA2 mutation who developed erythema nodosum after initiation of therapy with olaparib capsules. Her characteristic rash appeared shortly after starting olaparib and recurred after restarting olaparib an additional two times. She was treated with short courses of prednisone therapy with or without holding olaparib with resolution of her rash. The patient was later restarted on olaparib capsules 200 mg twice daily, and she more recently has been maintained on olaparib tablets 300 mg twice daily. On both regimens, the patient experienced only attenuated episodes of erythema nodosum that have not required cessation of therapy or steroid therapy.

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

“…Erythema nodosum may arise from a delayed hypersensitivity response 23 . In the abovementioned case report of olaparib for metastatic BC, erythema nodosum lessened after switching from capsule to tablet formulation, which the authors suggested could be related to the higher bioavailability and longer half‐life of the tablet formulation 23 .…”

“…In 2018, a case of metastatic BC responding to olaparib at 300 mg BID reported erythema nodosum as a novel AE 23 . The nodules resolved completely after withholding olaparib and applying prednisone.…”

“…Erythema nodosum may arise from a delayed hypersensitivity response 23 . In the abovementioned case report of olaparib for metastatic BC, erythema nodosum lessened after switching from capsule to tablet formulation, which the authors suggested could be related to the higher bioavailability and longer half‐life of the tablet formulation 23 . Note also that erythema nodosum can be paraneoplastic and caused by an altered immune response to malignancy, which has previously been linked to certain forms of lymphomas, leukemia, and solid tumors 33 …”

Olaparib-Induced Purpuric Drug Eruption in a Patient with Castration-Resistant Prostate Cancer

“…BRCA1 and BRCA2 are well-characterized genes involved in homologous recombination repair, and BRCA1 mutation was detected in the present case. Since olaparib is a newly approved drug, case reports of olaparib-induced skin disorders are limited; only erythema nodosum and cutaneous arteritis have been previously reported [3][4][5]. Notably, these previous reports indicate that skin lesions mainly appear on the extremities [3][4][5].…”

Real-world data in patients with BRCA mutated breast cancer treated with poly (ADP-ribose) polymerase inhibitors

“…The median onset time of reported adverse events was 61 days; most events occurred in the first 3 months since olaparib initiation. Other novel adverse events have been described in case reports of patients with MBC with a BRCA1/2 mutation, including recurrent episodes of erythema nodosum, which may be managed through dose reductions [ 40 ].…”