Introducción La incidencia de melanoma cutáneo ha aumentado a nivel mundial con el paso de los años, estimándose en Chile una incidencia de 3 casos por 100.000 hombres y mujeres. Aunque la mayoría de los pacientes son diagnosticados en etapas tempranas de la enfermedad y tienen un buen pronóstico, el melanoma avanzado tiene malos resultados de sobrevida. Para el tratamiento del melanoma, se ha demostrado que la combinación de dabrafenib más trametinib mejora el resultado frente a dabrafenib solo, pero sólo se dispone de evidencia indirecta sobre su eficacia y seguridad en comparación con la inmunoterapia, como nivolumab. Métodos Se realizaron búsquedas en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, que se mantiene mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Se extrajeron los datos de las revisiones sistemáticas seleccionadas, se reanalizaron los datos de los estudios primarios y se generó una tabla de resumen de los hallazgos utilizando el enfoque GRADE. Resultados y conclusiones Se identificaron cinco revisiones sistemáticas, incluyendo siete estudios en total que incluían una intervención de nuestro interés, de los cuales todos eran ensayos aleatorizados. Se concluyó que no es posible decidir si dabrafenib más trametinib es una mejor estrategia para el tratamiento del melanoma avanzado que nivolumab porque la certeza de las pruebas es muy baja para los resultados de eficacia y seguridad.

BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. RESULTS: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

RECORD STATUS: This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. CITATION: NIHR HSC. Nivolumab for non-small cell lung cancer – second line. Birmingham: NIHR Horizon Scanning Centre (NIHR HSC). Horizon Scanning Review. 2013

BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. CONCLUSIONS: The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.

BACKGROUND: Nivolumab has become a therapeutic regimen for the treatment of patients with advanced melanoma. The goal of this study was to assess the efficacy and safety of nivolumab in patients with advanced melanoma. METHODS: A systematic search from January 2008 to August 2015 with "nivolumab" and "advanced melanoma" as search terms was performed for possible clinical trials. According to the hazard ratio and the 95% confidence interval (CI) for progression-free survival (PFS), rates of objective response, complete response, partial response, rates of toxic effects, and the efficacy and safety of nivolumab were assessed. Using the software Review Manager (version 5.3) a meta-analysis was performed. RESULTS: There were four trials with 1,910 patients included. Based on the four trials, the pooled hazard ratio of PFS was 0.53 (95% CI, 0.43-0.66; P<0.001). The pooled risk ratio for the objective response rate, complete response, and partial response was 2.98% (95% CI, 2.38%-3.73%; P<0.001), 3.71% (95% CI, 2.67%-5.14%; P<0.001), and 2.51% (95% CI, 2.12%-2.99%; P<0.001), respectively. Nivolumab plus ipilimumab therapy significantly increased the risk of grade 3/4 rash and fatigue. CONCLUSION: Nivolumab-based therapy prolonged PFS in treatment of advanced melanoma, with less adverse effects. Nivolumab appears to be a favorable treatment option as a novel, targeted anticancer agent, for patients with advanced melanoma.

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PURPOSE: The aim of this study was to evaluate the risk of immune-related adverse events (irAEs) among cancer patients receiving nivolumab-plus-ipilimumab therapy and nivolumab monotherapy. PATIENTS AND METHODS: PubMed and Web of Science were searched for related studies from inception to June 2018. Eligible studies included randomized controlled trials comparing nivolumab-plus-ipilimumab with nivolumab alone in cancer patients reporting on all-grade (grade 1-4) and high-grade (grade 3/4) irAEs. Paired reviewers selected studies for inclusion and extracted data. The odds risk and 95% CI were calculated. RESULTS: A total of 2,946 patients from four studies were included in the meta-analysis. The underlying malignancies included lung cancer (two trials) and melanoma (two trials). Compared with nivolumab monotherapy, the nivolumab-plus-ipilimumab therapy was associated with a significantly higher risk of all- and high-grade irAEs such as pruritus, rash, diarrhea, colitis, alanine aminotransferase elevation, and pneumonitis. CONCLUSION: The combination therapy of nivolumab and ipilimumab increased the incidence of irAEs in patients with advanced cancer.

This is an investigational study. Nivolumab is FDA approved to treat metastatic melanoma or non-small cell lung cancer after the disease has gotten worse while receiving platinum-based chemotherapy. Ipilimumab is FDA approved to treat metastatic melanoma. The use of nivolumab and ipilimumab in this study is investigational. Bevacizumab is approved for certain types of kidney cancer and several other types of cancer, including breast, colon, and lung cancer. It is not FDA approved for the treatment of metastatic kidney cancer. The use of bevacizumab in this study is investigational. The study doctor can explain how the study drug(s) are designed to work. Up to 105 participants will take part in this study. All will be enrolled at MD Anderson.

The present study aims to demonstrate if the addition of axitinib to nivolumab maintenance after nivolumab plus ipilimumab induction can improve the rate of response considering that the incidence of partial response was 32% and 51% in Checkmate214 and Keynote426 trials respectively. This study requires 106 patients to show an improvement from 30% to 50% of the incidence of partial responses with a power of 80%, and alpha‐error 0.10 (one‐side p). Assuming a drop out of 10%, the final estimated number to enroll should be 118 (59 in arm A and 59 in arm B).