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Vol. 53. Issue 12.
Pages 682-687 (December 2017)
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Vol. 53. Issue 12.
Pages 682-687 (December 2017)
Review
New Immunotherapy and Lung Cancer
Nueva inmunoterapia y cáncer de pulmón
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8843
Julio Sánchez de Cos Escuín
Servicio de Neumología, Hospital San Pedro de Alcántara, Cáceres, Spain
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Tables (4)
Table 1. Immune Checkpoint Inhibitors Used in LC and Their Specific Targets.
Table 2. Immune Checkpoint Inhibitors (ICI) in Advanced NSCLC Randomized Trials After Relapse.
Table 3. Anti-PD-1 and Anti-PD-L1 Immune Checkpoint Inhibitors Adverse Effects in Randomized Trials in LC Patients.
Table 4. Randomized First-Line Trials With Immune Checkpoint Inhibitors (ICI) in Advanced NSCLC Patients Positive for PD-L1.
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Abstract

Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response.

These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%–25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results.

This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents.

Keywords:
Immunotherapy
Lung cancer
Immune checkpoint inhibitors
Resumen

Investigaciones recientes sobre la relación entre el sistema inmune y el cáncer han desvelado los mecanismos moleculares mediante los cuales las células neoplásicas aprovechan algunos receptores de los linfocitos T, con función inhibitoria de la respuesta citotóxica, para defenderse del ataque inmune desarrollado frente a ellas. Estos hallazgos han permitido identificar dianas precisas (receptores de los linfocitos T o ligandos que se acoplan a ellos) frente a los que se han diseñado anticuerpos monoclonales, capaces de desbloquear la respuesta inmunitaria.

Estos fármacos (immune check point inhibitors), de eficacia demostrada en el melanoma metastásico o el carcinoma renal, han sido probados con éxito frente al carcinoma de pulmón no microcítico en ensayos recientes. Tras su aprobación e incorporación a la práctica clínica en 2.ª línea después de una pauta inicial de quimioterapia (QT), se han comunicado en el último año resultados positivos en ensayos aleatorizados que los comparaban con QT estándar en 1.ª línea. Se han observado respuestas sorprendentes y duraderas, aunque no superan el 20-25% en pacientes no seleccionados, por lo que es crucial detectar rasgos predictivos de eficacia, como el biomarcador PD-L1, si bien los diferentes métodos para su detección han producido resultados dispares.

En esta revisión no sistemática se discuten los resultados de los últimos ensayos, las posibilidades de incorporar estos fármacos en primera línea, los criterios de selección de pacientes, los efectos adversos y las perspectivas de su empleo asociados a modalidades terapéuticas tradicionales como QT, radioterapia o antiangiogénicos.

Palabras clave:
Inmunoterapia
Cáncer de pulmón
Inmunodesbloqueadores

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