A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer
Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00195/full |
| _version_ | 1830161990835765248 |
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| author | Jose M. Pacheco D. Ross Camidge Robert C. Doebele Erin Schenk |
| author_facet | Jose M. Pacheco D. Ross Camidge Robert C. Doebele Erin Schenk |
| author_sort | Jose M. Pacheco |
| collection | DOAJ |
| description | Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data. |
| first_indexed | 2024-12-17T15:11:19Z |
| format | Article |
| id | doaj.art-0fe350ac38ca418391a06dd0cafc21b3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T15:11:19Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0fe350ac38ca418391a06dd0cafc21b32022-12-21T21:43:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-03-01910.3389/fonc.2019.00195454255A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung CancerJose M. PachecoD. Ross CamidgeRobert C. DoebeleErin SchenkInhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data.https://www.frontiersin.org/article/10.3389/fonc.2019.00195/fullNSCLCcheckpoint inhibitorsclinical trialsKEYNOTECheckMateIMpower |
| spellingShingle | Jose M. Pacheco D. Ross Camidge Robert C. Doebele Erin Schenk A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer Frontiers in Oncology NSCLC checkpoint inhibitors clinical trials KEYNOTE CheckMate IMpower |
| title | A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer |
| title_full | A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer |
| title_fullStr | A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer |
| title_full_unstemmed | A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer |
| title_short | A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer |
| title_sort | changing of the guard immune checkpoint inhibitors with and without chemotherapy as first line treatment for metastatic non small cell lung cancer |
| topic | NSCLC checkpoint inhibitors clinical trials KEYNOTE CheckMate IMpower |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00195/full |
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