First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Exergame training-induced neuroplasticity and cognitive improvement in institutionalized older adults: A preliminary investigation.

BACKGROUND: Prior research has reported cognitive improvements in elderly individuals when mental and physical exercise are practiced simultaneously, as in exergaming. However, the molecular mechanisms driving this beneficial response remain unclear. Moreover, there is robust evidence that regular exercise increases neurotrophic factors and promotes neuroplasticity, contributing to cognitive improvement. This research aimed to assess the impact of a 6-week Xbox 360 Kinect exergame protocol on cognitive function and brain-derived neurotrophic factor (BDNF) levels in institutionalized older individuals. METHODS: Participants living in a long-term care facility were included. The intervention (Xbox 360 Kinect exergame protocol) was conducted individually and consisted of two sessions per week (40 min each) over 6 weeks. Participants' cognitive function (Montreal Cognitive Assessment, MoCA) was evaluated before and after the intervention. Blood samples (15 ml) were collected at the same time to measure BDNF levels. RESULTS: Although there were no changes in total MoCA scores, exergame training improved the "language" domain and demonstrated a tendency toward an improvement in the "abstraction" and "memory/delayed recall" domains. Furthermore, BDNF levels were significantly increased after the intervention. CONCLUSION: BDNF enhancement might mediate, at least in part, the cognitive changes induced by a 6-week Xbox 360 Kinect exergame protocol in institutionalized older adults.