Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers.

BACKGROUND: The programmed death-ligand 1 inhibitor atezolizumab had shown clinical activity against several advanced malignancies. PATIENTS AND METHODS: This phase II, open-label basket study (NCT02458638) was conducted in 16 main cohorts of patients aged ≥18 years with stage III or IV solid tumors. In stage I, 12 patients were enrolled into each cohort. Treatment was atezolizumab 1200 mg intravenously every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary efficacy endpoint was the non-progression rate (NPR) at 18 weeks in treated, assessable patients. NPR ≤20% was not of interest for development as monotherapy, and NPR ≥40% was defined as the threshold of benefit/success. If ≥3 patients had non-progressive disease in stage I (interim analysis), 13 additional patients could be enrolled into stage II (final analysis). Secondary efficacy and safety endpoints were also evaluated. RESULTS: Overall, 474 patients were enrolled and treated; 433 were included in the efficacy set. Due partly to slow recruitment because of competing trials and limited efficacy at interim analyses, enrollment was stopped early, including in cohorts that passed stage I boundaries of success. NPR was >20% in five cohorts: cervical cancer {n = 27; NPR 44.4% [95% confidence interval (CI) 25.5% to 64.7%]}; follicular/papillary thyroid cancer [n = 11; 54.5% (95% CI 23.4% to 83.3%)]; thymoma [n = 13; 76.9% (95% CI: 46.2% to 95.0%)]; gastroenteropancreatic (GEP) and lung neuroendocrine tumors [NETs; n = 24; 41.7% (95% CI 22.1% to 63.4%)], and low/intermediate grade carcinoid GEP and lung NETs [n = 12; 58.3% (95% CI 27.7% to 84.8%)]. Treatment-related adverse events occurred in 55.3% of patients overall, and at grade 3, 4, and 5 in 10.3%, 1.7%, and 0.4%, respectively. CONCLUSIONS: Atezolizumab monotherapy was effective in the cervical cancer cohort. The interim benefit threshold was crossed in patients with follicular/papillary thyroid cancer, thymoma, and GEP and lung NETs, but recruitment was stopped before these signals could be confirmed in stage II. Safety was consistent with previous findings.

Reporte de caso de enfermedad mano-pie-boca con lesiones mucocutáneas que evolucionan a necrosis / A case report of hand, foot, and mouth disease with necrotizing mucocutaneous lesions

La enfermedad de mano-pie-boca es una patología originada en la mayoría de los casos por el virus coxsackie A tipo 16, aunque también puede ser ocasionada por otras cepas de la familia de los coxsackievirus. Dicho virus se propaga principalmente por vía fecal oral y, en menor proporción, por secreciones. Se presenta principalmente en verano, siendo frecuente en niños menores de 10 años. Dentro de dicha enfermedad las lesiones mucocutáneas que evolucionen en necrosis son poco frecuentes, constituyéndose en una complicación severa que requiere hospitalización. En el presente artículo se reporta un caso con diagnóstico de enfermedad mano-pie-boca, que evolucionó hacia lesiones mucocutáneas necróticas, mostrando una respuesta favorable a una terapia de soporte de aciclovir, líquidos y electrolitos.

In most cases, the cause of hand, foot, and mouth disease (HFMD) is coxsackievirus A type 16. The infection can also be caused by other strains of coxsackievirus, spreading mainly by the oral-fecal route, while it is less likely to be transmitted through secretions. HFMD occurs mainly in summer and is more common in children under ten. Skin lesions develop during the disease but rarely become necrotic. When present, they are a severe complication requiring hospitalization. This paper reports the case of a patient with HFMD who developed necrotic mucocutaneous lesions that responded favorably to intravenous acyclovir, fluids, and electrolyte support therapy.