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Immunotherapy in Small Cell Lung Cancer

SIMPLE SUMMARY: Small cell lung cancer (SCLC) accounts for about 15% of lung cancers and it has limited therapeutic options and poor prognosis. There has been no real progress for over 30 years in the treatment of this aggressive tumor type and platinum based chemotherapy represented the cornerstone...

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Autores principales: Esposito, Giovanna, Palumbo, Giuliano, Carillio, Guido, Manzo, Anna, Montanino, Agnese, Sforza, Vincenzo, Costanzo, Raffaele, Sandomenico, Claudia, La Manna, Carmine, Martucci, Nicola, La Rocca, Antonello, De Luca, Giuseppe, Piccirillo, Maria Carmela, De Cecio, Rossella, Botti, Gerardo, Totaro, Giuseppe, Muto, Paolo, Picone, Carmine, Normanno, Nicola, Morabito, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565004/
https://www.ncbi.nlm.nih.gov/pubmed/32899891
http://dx.doi.org/10.3390/cancers12092522
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author Esposito, Giovanna
Palumbo, Giuliano
Carillio, Guido
Manzo, Anna
Montanino, Agnese
Sforza, Vincenzo
Costanzo, Raffaele
Sandomenico, Claudia
La Manna, Carmine
Martucci, Nicola
La Rocca, Antonello
De Luca, Giuseppe
Piccirillo, Maria Carmela
De Cecio, Rossella
Botti, Gerardo
Totaro, Giuseppe
Muto, Paolo
Picone, Carmine
Normanno, Nicola
Morabito, Alessandro
author_facet Esposito, Giovanna
Palumbo, Giuliano
Carillio, Guido
Manzo, Anna
Montanino, Agnese
Sforza, Vincenzo
Costanzo, Raffaele
Sandomenico, Claudia
La Manna, Carmine
Martucci, Nicola
La Rocca, Antonello
De Luca, Giuseppe
Piccirillo, Maria Carmela
De Cecio, Rossella
Botti, Gerardo
Totaro, Giuseppe
Muto, Paolo
Picone, Carmine
Normanno, Nicola
Morabito, Alessandro
author_sort Esposito, Giovanna
collection PubMed
description SIMPLE SUMMARY: Small cell lung cancer (SCLC) accounts for about 15% of lung cancers and it has limited therapeutic options and poor prognosis. There has been no real progress for over 30 years in the treatment of this aggressive tumor type and platinum based chemotherapy represented the cornerstone of therapy. Immune checkpoint inhibitors are the first agents in the last decades to determine an improvement in outcomes of patients with extensive stage (ES) SCLC patients. In the IMpower 133 and CASPIAN studies, the addition of atezolizumab or durvalumab, respectively, to first-line chemotherapy produced a significant improvement in overall survival with an acceptable safety profile in previously untreated patients with ES-SCLC, leading to a new standard of care. This review summarizes the main results observed with checkpoint inhibitors in SCLC, discussing the critical issues related to the use of novel checkpoint inhibitors and the future research with immunotherapy agents in SCLC. ABSTRACT: Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.
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spelling pubmed-75650042020-10-26 Immunotherapy in Small Cell Lung Cancer Esposito, Giovanna Palumbo, Giuliano Carillio, Guido Manzo, Anna Montanino, Agnese Sforza, Vincenzo Costanzo, Raffaele Sandomenico, Claudia La Manna, Carmine Martucci, Nicola La Rocca, Antonello De Luca, Giuseppe Piccirillo, Maria Carmela De Cecio, Rossella Botti, Gerardo Totaro, Giuseppe Muto, Paolo Picone, Carmine Normanno, Nicola Morabito, Alessandro Cancers (Basel) Review SIMPLE SUMMARY: Small cell lung cancer (SCLC) accounts for about 15% of lung cancers and it has limited therapeutic options and poor prognosis. There has been no real progress for over 30 years in the treatment of this aggressive tumor type and platinum based chemotherapy represented the cornerstone of therapy. Immune checkpoint inhibitors are the first agents in the last decades to determine an improvement in outcomes of patients with extensive stage (ES) SCLC patients. In the IMpower 133 and CASPIAN studies, the addition of atezolizumab or durvalumab, respectively, to first-line chemotherapy produced a significant improvement in overall survival with an acceptable safety profile in previously untreated patients with ES-SCLC, leading to a new standard of care. This review summarizes the main results observed with checkpoint inhibitors in SCLC, discussing the critical issues related to the use of novel checkpoint inhibitors and the future research with immunotherapy agents in SCLC. ABSTRACT: Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents. MDPI 2020-09-04 /pmc/articles/PMC7565004/ /pubmed/32899891 http://dx.doi.org/10.3390/cancers12092522 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Esposito, Giovanna
Palumbo, Giuliano
Carillio, Guido
Manzo, Anna
Montanino, Agnese
Sforza, Vincenzo
Costanzo, Raffaele
Sandomenico, Claudia
La Manna, Carmine
Martucci, Nicola
La Rocca, Antonello
De Luca, Giuseppe
Piccirillo, Maria Carmela
De Cecio, Rossella
Botti, Gerardo
Totaro, Giuseppe
Muto, Paolo
Picone, Carmine
Normanno, Nicola
Morabito, Alessandro
Immunotherapy in Small Cell Lung Cancer
title Immunotherapy in Small Cell Lung Cancer
title_full Immunotherapy in Small Cell Lung Cancer
title_fullStr Immunotherapy in Small Cell Lung Cancer
title_full_unstemmed Immunotherapy in Small Cell Lung Cancer
title_short Immunotherapy in Small Cell Lung Cancer
title_sort immunotherapy in small cell lung cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565004/
https://www.ncbi.nlm.nih.gov/pubmed/32899891
http://dx.doi.org/10.3390/cancers12092522
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