The impact of the 2022 Ukraine/Russian conflict on cancer clinical trials.

Since the invasion of Ukraine in February 2022, clinical trial conduct has become extremely challenging due to damage to the healthcare infrastructure and patient displacement. This current study aimed to estimate the number of cancer clinical trials at risk of impact from the conflict. A descriptive analysis and narrative review were completed using data from cancer clinical trials with sites in Russia or Ukraine using the 'clinical trials.gov' online database between February 2022 and May 2022. There were 508 clinical trials involving sites in Ukraine or Russia. Most were multinational studies (470 of 508; 93%). The majority of studies were phase 3 (344 of 508; 68%) and these also had the largest sample sizes (median 624, range 12-5637). The most common tumour types were lung (128 of 508; 25%), urogenital (94 of 508; 19%) and breast (78 of 508; 15%). A meaningful number of trials had curative intent (129 of 508; 25%). The most common intervention was immunotherapy-related (218 of 508; 43%), followed by other targeted therapy (185 of 508; 36%). Ukraine and Russia are both large centres for global clinical trial activity. The invasion of Ukraine may result in underpowering of international clinical trial results with loss of future recruitment sites for both countries.

Pulmonary arterial hypertension outcomes upon endothelin-1 receptor antagonist switch to macitentan.

OBJECTIVES: To assess whether switching patients with suboptimally controlled pulmonary arterial hypertension from bosentan or ambrisentan to macitentan would improve six-minute walk test (6MWT) distance and World Health Organization functional class. METHODS: This was a retrospective cohort analysis of 37 patients from a single center. Patients were separated into three heterogeneous treatment groups and followed for 18 months: switch group (n = 14): patients switched to macitentan from bosentan/ambrisentan; added group (n = 11): patients who began macitentan as de novo therapy (n = 5) or who added macitentan to an existing sildenafil regimen (n = 6); and control group (n = 12): patients for whom sildenafil and/or bosentan/ambrisentan therapy was unchanged. RESULTS: Mortality was observed in two patients (one each, switch and added groups). Patients in the control group had one hospital admission and 100% survival. There was significant improvement in functional class for the switch and added groups. Statistically significant improvement was observed in 6MWT distance in the added group alone. Overall, 92% of patients continued macitentan throughout the study. CONCLUSION: Macitentan was well tolerated. For bosentan/ambrisentan-treated patients with suboptimally controlled pulmonary arterial hypertension, switching to macitentan may facilitate an improvement in functional class.