Locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) has poor prognosis following platinum-based chemotherapy. Retifanlimab (INCMGA00012), a humanized monoclonal antibody ...targeting programmed death protein-1 (PD-1), demonstrated clinical activity across a range of solid tumors in clinical trials. We present results from POD1UM-202 (NCT03597295), an open-label, single-arm, multicenter, phase II study evaluating retifanlimab in patients with previously treated advanced or metastatic SCAC.
Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% 95% confidence interval (CI) 7.6% to 22.5%, with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class.
Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.
•Retifanlimab (PD-1 inhibitor) monotherapy demonstrated encouraging results in patients with platinum-refractory SCAC.•Clinically meaningful antitumor activity was reported with ORR of 13.8% and stable disease in 35.1%, for a DCR of 48.9%.•Observed responses in advanced SCAC were durable (median 9.5 months).•Acceptable safety profile consistent with that reported for the PD-(L)1 inhibitor class.•Promising results warrant further investigation of retifanlimab in advanced SCAC as well as earlier stages of disease.
Neuroendocrine tumors (NETs) represent a heterogeneous group of diseases with varied natural history and prognosis depending upon the organ of origin and grade of aggressiveness. The most widely used ...biomarker to determine disease burden and monitor response to treatment is chromogranin A (CgA), but it is far from being the optimal predictive and prognostic biomarker in NETs. Biological understanding and derived treatment options for NETs have changed markedly in recent years. Over the last decade, the genomic landscape of these tumors has been extensively investigated. This has resulted in the discovery of mutations and expression anomalies in genes and pathways such as the PI3K/Akt/mTOR, DAXX/ATRX, and MEN1, which are promising predictive and prognostic biomarkers and future candidates for targeted therapies. Additionally, the study of tumor stroma and environment are one of the most promising fields for discovery of potential new targets and biomarkers.
Resumen Introducción y objetivos Los tumores neuroendocrinos generan un gran interés científico, dada la dificultad de su diagnóstico y tratamiento. A pesar de ser relativamente raros (<1/100,000 ...individuos, 1-2% de las neoplasias digestivas) e indolentes, no se debe olvidar que, en última instancia, son potencialmente malignos. En los últimos años, se ha observado un incremento en el número de tumores diagnosticados. El objetivo del estudio fue la actualización de una serie publicada de 19 casos con sospecha de tumor neuroendocrino pancreático, con otros 51 casos actuales, para el estudio y comparación de los nuevos resultados tanto con la serie anterior como con otras publicadas recientemente en España, Estados Unidos, China e India. Material y métodos Serie retrospectiva, multicéntrica de 70 pacientes (19 publicados en 2011) recopilados a lo largo de 23 años. Variables analizadas: edad, sexo, sintomatología, tamaño, localización, metástasis, diagnóstico final y cirugía, entre otras. Resultados Edad media de 55 años; 60% hombres; localización: cabeza (28.5%) y cola (27.1%); tamaño medio 3,9 cm (0,2-10 cm); no funcionantes el 71.4%; metástasis en el 32.8% (100% hepáticas), operados el 74.2% y supervivencia actuarial del 75%. Conclusiones Se observan diferencias entre la serie anteriormente publicada y los resultados actuales, con un incremento del porcentaje de incidentalomas y de tumores no funcionantes, pero sin variación en la tasa de supervivencia global. Con otras series actuales, las diferencias (edad, sexo y localización tumoral) dependen del país donde se han recopilado los casos. Este incremento podría relacionarse con el aumento del diagnóstico por la imagen y con la mayor la sensibilidad de los dispositivos.
Purpose
Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of low incidence neoplasms characterized by a low proliferative activity and slow growth. Their response to targeted ...therapies is heterogeneous and often does not lead to tumor shrinkage. Thus, evaluation of the therapeutic response should differ from other kind of tumors.
Methods
To answer relevant questions about which techniques are best in the assessment of progression or treatment response a RAND/UCLA-based consensus process was implemented. Relevant clinical questions were listed followed by a systematic search of the literature. The expert panel answered all questions with recommendations, combining available evidence and expert opinion. Recommendations were validated through a questionnaire and a participatory meeting.
Results
Expert recommendations regarding imaging tools for tumor assessment and evaluation of progression were agreed upon. Available imaging techniques were reviewed and recommendations for best patient monitoring practice and the best way to evaluate treatment response were formulated.
•Ultrasonic velocity correlates significantly with malic and lactic acid concentrations.•Ultrasonic velocity could be used to predict the end of the malolactic fermentation process.•Velocity of an ...ultrasonic pulse may be used to monitor the malolactic fermentation process.
During malolactic fermentation in wines, malic acid is transformed into lactic acid by the action of lactic acid bacteria. This process can be monitored on-line by measuring the velocity of a low intensity ultrasonic wave propagating through the medium. In this work, an experimental study of ultrasonic propagation velocity in laboratory mixtures of water–ethanol–malic acid and lactic acid is presented. A good correlation was found between the ultrasonic velocity and malic and lactic acid concentrations. These results could be used to predict the end-point of the malolactic fermentation process and show the great potential of this ultrasonic technique to determine malic and lactic acid concentrations during the malolactic fermentation process.
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