Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis
Three drug combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi), and avelumab-axitinib (Ave-Axi), have received regulatory approval in the USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comp...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/6/1673 |
| _version_ | 1797564243258638336 |
|---|---|
| author | Reza Elaidi Letuan Phan Delphine Borchiellini Philippe Barthelemy Alain Ravaud Stéphane Oudard Yann Vano |
| author_facet | Reza Elaidi Letuan Phan Delphine Borchiellini Philippe Barthelemy Alain Ravaud Stéphane Oudard Yann Vano |
| author_sort | Reza Elaidi |
| collection | DOAJ |
| description | Three drug combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi), and avelumab-axitinib (Ave-Axi), have received regulatory approval in the USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comparison data are available to identify the best option. Therefore, we aimed to compare these new treatments in a first-line setting. We conducted a systematic search in PubMed, the Cochrane Library, and clinicaltrials.gov for any randomized controlled trials of treatment-naïve patients with mRCC, from January 2015 to October 2019. The process was performed according to PRISMA guidelines. We performed a Bayesian network meta-analysis with two different approaches, a contrast-based model comparing HRs and ORs between studies and arm-based using parametric modeling. The outcomes for the analysis were overall survival, progression-free survival (PFS), and objective response rate. Our search identified 3 published phase 3 randomized clinical trials (2835 patients). In the contrast-based model, Ave-Axi (SUCRA = 83%) and Pembro-Axi (SUCRA = 80%) exhibited the best ranking probabilities for PFS. For overall survival (OS), Pembro-Axi (SUCRA = 96%) was the most preferable option against Ave-Axi and Ipi-Nivo. Objective response rate analysis showed Ave-Axi as the best (SUCRA: 94%) and Pembro-Axi as the second best option. In the parametric models, the risk of progression was comparable for Ave-Axi and Ipi-Nivo, whereas Pembro-Axi exhibited a lower risk during the first 6 months of treatment and a higher risk afterwards. Furthermore, Pembro-Axi exhibited a net advantage in terms of OS over the two other regimens, while Ave-Axi was the least preferable option. Overall evidence suggests that pembrolizumab plus axitinib seems to have a slight advantage over the other two combinations. |
| first_indexed | 2024-03-10T18:55:39Z |
| format | Article |
| id | doaj.art-be924ca459b34dbbbf00af4ea82d8759 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:55:39Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-be924ca459b34dbbbf00af4ea82d87592023-11-20T04:50:54ZengMDPI AGCancers2072-66942020-06-01126167310.3390/cancers12061673Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-AnalysisReza Elaidi0Letuan Phan1Delphine Borchiellini2Philippe Barthelemy3Alain Ravaud4Stéphane Oudard5Yann Vano6ARTIC (Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie), Hôpital Européen Georges Pompidou, 75015 Paris, FranceARTIC (Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie), Hôpital Européen Georges Pompidou, 75015 Paris, FranceDepartment of Medical Oncology, Centre Antoine-Lacassagne, 06100 Nice, FranceDepartment of Medical Oncology, Hôpital civil, 67091 Strasbourg, FranceDepartment of Medical Oncology, Hôpital St Andre, 33000 Bordeaux, FranceDepartment of Medical Oncology, Hôpital Européen Georges Pompidou, 75015 Paris, FranceDepartment of Medical Oncology, Hôpital Européen Georges Pompidou, 75015 Paris, FranceThree drug combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi), and avelumab-axitinib (Ave-Axi), have received regulatory approval in the USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comparison data are available to identify the best option. Therefore, we aimed to compare these new treatments in a first-line setting. We conducted a systematic search in PubMed, the Cochrane Library, and clinicaltrials.gov for any randomized controlled trials of treatment-naïve patients with mRCC, from January 2015 to October 2019. The process was performed according to PRISMA guidelines. We performed a Bayesian network meta-analysis with two different approaches, a contrast-based model comparing HRs and ORs between studies and arm-based using parametric modeling. The outcomes for the analysis were overall survival, progression-free survival (PFS), and objective response rate. Our search identified 3 published phase 3 randomized clinical trials (2835 patients). In the contrast-based model, Ave-Axi (SUCRA = 83%) and Pembro-Axi (SUCRA = 80%) exhibited the best ranking probabilities for PFS. For overall survival (OS), Pembro-Axi (SUCRA = 96%) was the most preferable option against Ave-Axi and Ipi-Nivo. Objective response rate analysis showed Ave-Axi as the best (SUCRA: 94%) and Pembro-Axi as the second best option. In the parametric models, the risk of progression was comparable for Ave-Axi and Ipi-Nivo, whereas Pembro-Axi exhibited a lower risk during the first 6 months of treatment and a higher risk afterwards. Furthermore, Pembro-Axi exhibited a net advantage in terms of OS over the two other regimens, while Ave-Axi was the least preferable option. Overall evidence suggests that pembrolizumab plus axitinib seems to have a slight advantage over the other two combinations.https://www.mdpi.com/2072-6694/12/6/1673metastatic renal cell carcinomaimmune-based combination therapiesnetwork meta-analysis |
| spellingShingle | Reza Elaidi Letuan Phan Delphine Borchiellini Philippe Barthelemy Alain Ravaud Stéphane Oudard Yann Vano Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis Cancers metastatic renal cell carcinoma immune-based combination therapies network meta-analysis |
| title | Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis |
| title_full | Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis |
| title_fullStr | Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis |
| title_full_unstemmed | Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis |
| title_short | Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis |
| title_sort | comparative efficacy of first line immune based combination therapies in metastatic renal cell carcinoma a systematic review and network meta analysis |
| topic | metastatic renal cell carcinoma immune-based combination therapies network meta-analysis |
| url | https://www.mdpi.com/2072-6694/12/6/1673 |
| work_keys_str_mv | AT rezaelaidi comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT letuanphan comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT delphineborchiellini comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT philippebarthelemy comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT alainravaud comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT stephaneoudard comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis AT yannvano comparativeefficacyoffirstlineimmunebasedcombinationtherapiesinmetastaticrenalcellcarcinomaasystematicreviewandnetworkmetaanalysis |