Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial.

BACKGROUND: The primary analysis of the phase III NIBIT-M2 study showed a 41% 4-year overall survival (OS) of melanoma patients with asymptomatic brain metastases treated with ipilimumab plus nivolumab. METHODS: Here, we report the 7-year efficacy outcomes and the Health-Related Quality of Life (HRQoL) analyses of the NIBIT-M2 study. RESULTS: As of May 1, 2023, at a median follow-up of 67 months (mo), the median OS was 8.5 (95% CI: 6.6-10.3), 8.2 (95% CI: 2.1-14.3) and 29.2 (95% CI: 0-69.9) mo for the fotemustine (F) Arm A, ipilimumab plus fotemustine Arm B, and ipilimumab plus nivolumab Arm C, respectively. The 7-year OS rate was 10.0% (95% CI: 0-22.5) in Arm A, 10.3% (95% CI: 0-22.6) in Arm B, and 42.8% (95% CI: 23.4-62.2) in Arm C. HRQoL was preserved in all treatment arms. Most functional scales evaluated from baseline to W12 were preserved, with a lower mean score decrease for EORTC Quality of Life Questionnaire (QLQ)-C30 and an increase for EORTC QLQ-Brain neoplasm (BN20) in patients receiving ipilimumab plus nivolumab. CONCLUSIONS: With the longest follow-up available to date in melanoma patients with asymptomatic brain metastases, the NIBIT-M2 study continues to show persistent therapeutic efficacy of I ipilimumab plus nivolumab while preserving HRQoL.

Successful Targeting of CTLA-4 in a Melanoma Clinical Case: A Long-Term "One Stop Therapeutic Shop".

The anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) monoclonal antibody ipilimumab was the first in-class immune-checkpoint inhibitor (ICI) approved for the treatment of melanoma patients. Initially approved for metastatic cutaneous melanoma, treatment with ipilimumab subsequently demonstrated to significantly improve recurrence free survival (RFS) in fully resected, high-risk, stage III melanoma patients. Therapeutic use of ipilimumab has also allowed the initial identification and characterization of unconventional clinical and radiological patterns of response (ie, tumor flare, pseudo-progression) that may occur during ICI therapy, unlike chemotherapy or targeted therapy. As a result, the standard Response Evaluation Criteria In Solid Tumors (RECIST) and the World Health Organization (WHO) criteria conventionally utilized to assess responses to chemo/targeted therapy have been initially replaced by the immune-related (ir) Response Criteria (irRC) and then by the irRECIST, that encompass all patterns of response typical of ICI therapy, being key for the optimal comprehensive management of treated patients. Here, we report a paradigmatic clinical case of a long-term survival in a stage III melanoma patient, experiencing tumor flares during adjuvant treatment with ipilimumab, and an untreated disease relapse several years after ending therapy.

Women and Pensions in Italy: Gender Imbalances and the Equalization of Retirement Age.

This paper examines the age at retirement for men and women in Italy. Despite the expansion of women's educational attainments, they still display lower employment rates, are frequently engaged in involuntary part-time jobs and have more fragmented careers. As a consequence, the mean age at which women receive a pension is higher than that of men. Using Labour Force Survey (2006 and 2012), the authors test the hypothesis that women's higher age at retirement is determined by a selection bias towards more educated and work oriented women. A Heckman selection model has been developed. Results show that the main disadvantage is suffered by women with medium and low levels of education who show the highest estimated age at retirement, whereas higher educated women retire on average before men with the same level of education. The authors argue that pension policies, without interventions in the field of work-life balance policies, end up penalizing women with lower levels of education.