Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.

BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.

Clinical evaluation of the use of exemestane as further hormonal therapy after nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer patients.

OBJECTIVES: The aromatase inhibitors Anastrozole, Letrozole (type 2 nonsteroidal aromatase inhibitors: n-SAI) and Exemestane (type 1 steroidal aromatase inactivator) are used respectively as first- and second-line hormonal therapy in postmenopausal metastatic breast cancer women. Few clinical data are published on the sequential use of different classes of aromatase inhibitors. METHODS: We report an analysis on 30 postmenopausal metastatic breast cancer women treated between January 2000 and May 2002 in 2 Italian Oncology Institutions with the hormonal sequence n-SAI (Anastrozole, Letrozole) --> Exemestane. RESULTS: When receiving n-SAI (Anastrozole 8 patients and Letrozole 22 patients), 1 out of 30 women achieved a partial response, 20 of 30 patients no change (NC) > or =6 months. The analysis of the entire population treated with Exemestane showed an overall clinical benefit (CB) of 46.6 percent (14/30) with a median duration of 12 months (95%CI 6-25) and a median time to progression (TTP) of 4 months (95%CI 1-25). CONCLUSIONS: These data confirm a partial lack of cross-resistance between n-SAI --> Exemestane given in sequence.