Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer
Oncology research has changed extensively due to the possibility to categorize each cancer type into smaller subgroups based on histology and particularly on different genetic alterations due to their heterogeneity. The consequences of this heterogeneity are particularly evident in the management of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Journal of Molecular Pathology |
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| Online Access: | https://www.mdpi.com/2673-5261/2/3/18 |
| _version_ | 1797518645725757440 |
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| author | Antonio Rossi Sara Pilotto Luisa Carbognin Miriam Grazia Ferrara Lorenzo Belluomini Gennaro Daniele Emilio Bria |
| author_facet | Antonio Rossi Sara Pilotto Luisa Carbognin Miriam Grazia Ferrara Lorenzo Belluomini Gennaro Daniele Emilio Bria |
| author_sort | Antonio Rossi |
| collection | DOAJ |
| description | Oncology research has changed extensively due to the possibility to categorize each cancer type into smaller subgroups based on histology and particularly on different genetic alterations due to their heterogeneity. The consequences of this heterogeneity are particularly evident in the management of metastatic non-small-cell lung cancer (NSCLC). This review will discuss the benefits and challenges of incorporating precision medicine into early- through late-phase metastatic NSCLC clinical trials, discussing examples of drug development programs in oncogene- and non-oncogene-addicted NSCLC. The experiences of clinical development of crizotinib, gefitinib and osimertinib are depicted showing that when a targeted drug is administrated in a study population not selected by any biomarker, trials could produce negative results. However, the early detection of biomarker-driven biology helps to obtain a greater benefit for a selected population and can reduce the required time for drug approval. Early clinical development programs involving nivolumab, pembrolizumab and avelumab, immune checkpoint inhibitors, taught us that, beyond safety and activity, the optimal selection of patients should be based on pre-specified biomarkers. Overall, the identification of predictive biomarkers is one of the greatest challenges of NSCLC research that should be optimized with solid methodological trial designs to maximize the clinical outcomes. |
| first_indexed | 2024-03-10T07:32:39Z |
| format | Article |
| id | doaj.art-2a7116bd5f5e488abb1fc87b82870ba8 |
| institution | Directory Open Access Journal |
| issn | 2673-5261 |
| language | English |
| last_indexed | 2024-03-10T07:32:39Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Molecular Pathology |
| spelling | doaj.art-2a7116bd5f5e488abb1fc87b82870ba82023-11-22T13:45:13ZengMDPI AGJournal of Molecular Pathology2673-52612021-06-012320722210.3390/jmp2030018Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung CancerAntonio Rossi0Sara Pilotto1Luisa Carbognin2Miriam Grazia Ferrara3Lorenzo Belluomini4Gennaro Daniele5Emilio Bria6Therapeutic Science & Strategy Unit, IQVIA, 20124 Milan, ItalyMedical Oncology, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) di Verona, 37100 Verona, ItalyDepartment of Woman and Child Health and Public Health, Woman Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00100 Rome, ItalyComprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, ItalyMedical Oncology, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) di Verona, 37100 Verona, ItalyScientific Directorate, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, ItalyComprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, ItalyOncology research has changed extensively due to the possibility to categorize each cancer type into smaller subgroups based on histology and particularly on different genetic alterations due to their heterogeneity. The consequences of this heterogeneity are particularly evident in the management of metastatic non-small-cell lung cancer (NSCLC). This review will discuss the benefits and challenges of incorporating precision medicine into early- through late-phase metastatic NSCLC clinical trials, discussing examples of drug development programs in oncogene- and non-oncogene-addicted NSCLC. The experiences of clinical development of crizotinib, gefitinib and osimertinib are depicted showing that when a targeted drug is administrated in a study population not selected by any biomarker, trials could produce negative results. However, the early detection of biomarker-driven biology helps to obtain a greater benefit for a selected population and can reduce the required time for drug approval. Early clinical development programs involving nivolumab, pembrolizumab and avelumab, immune checkpoint inhibitors, taught us that, beyond safety and activity, the optimal selection of patients should be based on pre-specified biomarkers. Overall, the identification of predictive biomarkers is one of the greatest challenges of NSCLC research that should be optimized with solid methodological trial designs to maximize the clinical outcomes.https://www.mdpi.com/2673-5261/2/3/18clinical trialsimmunotherapyimmune checkpoint inhibitorsnon-small cell lung cancertargeted therapytyrosine kinase inhibitors |
| spellingShingle | Antonio Rossi Sara Pilotto Luisa Carbognin Miriam Grazia Ferrara Lorenzo Belluomini Gennaro Daniele Emilio Bria Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer Journal of Molecular Pathology clinical trials immunotherapy immune checkpoint inhibitors non-small cell lung cancer targeted therapy tyrosine kinase inhibitors |
| title | Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer |
| title_full | Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer |
| title_fullStr | Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer |
| title_short | Modern Challenges for Early-Phase Clinical Trial Design and Biomarker Discovery in Metastatic Non-Small-Cell Lung Cancer |
| title_sort | modern challenges for early phase clinical trial design and biomarker discovery in metastatic non small cell lung cancer |
| topic | clinical trials immunotherapy immune checkpoint inhibitors non-small cell lung cancer targeted therapy tyrosine kinase inhibitors |
| url | https://www.mdpi.com/2673-5261/2/3/18 |
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