Extended duration of treatment using reduced-frequency dosing of anti-PD-1 therapy in patients with advanced melanoma and Merkel cell carcinoma.

BACKGROUND: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD). Receptor occupancy data supports reduced frequency dosing (RFD) of anti-PD-1 antibodies, which may represent a more practical and economically viable option to extend DoT. METHODS: We conducted a retrospective study of patients with metastatic melanoma and Merkel cell carcinoma (MCC), who received ICI at RFD administered every 3 months, after initial disease control at SFD. We evaluated efficacy, safety, and cost-savings of the RFD approach in this cohort. RESULTS: Between 2014 and 2021, 23 patients with advanced melanoma (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT was 1.1 years at SFD and 1.2 years at RFD. The 3 year PFS after start of RFD was 73% in melanoma and 100% in MCC patients, which compare favorably to historical control rates. In the subset of 15 patients who received at least 2 years of therapy, total savings amounted to $1.1 million in drug costs and 384 h saved despite the extended DoT (median 3.4 years), as compared to the calculated cost of 2 years at SFD. CONCLUSIONS: ICI administration at RFD can allow extension of treatment duration, while preserving efficacy and reducing logistical and financial burden. RFD approach deserves further exploration in prospective clinical trials.

Exemestane induced cholestatic liver injury - A case report.

PURPOSE: Exemestane, a steroidal aromatase inhibitor, is an important therapeutic option in the treatment of post-menopausal hormone receptor positive breast cancer. Adverse effects include hot flashes and bone loss, but rarely is hepatotoxicity reported. We report a case of exemestane induced cholestatic liver injury following exemestane initiation. CASE REPORT: A now 77-year-old Caucasian female with primary biliary cirrhosis (PBC), and metastatic hormone receptor positive breast cancer originally diagnosed in 2000 who developed symptoms of pruritus, diarrhea, grade 2 transaminitis, and grade 1 hyperbilirubinemia three weeks after exemestane initiation.Management and outcome: Due to the patient's signs and symptoms, exemestane was discontinued and the patient was continued on cholestyramine until resolution of her laboratory abnormalities. Approximately a week after discontinuation, the patient was started and maintained on anastrozole without recurrence of her symptoms. DISCUSSION: Hepatotoxicity with aromatase inhibitors have rarely been reported in clinical trials and to date, instances of exemestane induced hepatotoxicity has only been reported in two case reports. The patient's history of primary biliary cirrhosis may be an important risk factor for the development of hepatotoxicity from exemestane.