Mesenchymal–Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Eligibility Criteria
2.3. Search Strategy
2.4. Data Extraction and Risk of Bias Assessment
2.5. Statistical Analysis
3. Results
3.1. Study Selection and Characteristics
3.2. Objective Response Rate
3.3. Disease Control Rate
3.4. Progression-Free Survival
3.5. Survival Rate
3.6. Adverse Events
3.7. Quality Assessment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Compound | Molecular Formula | Mechanism of Action |
---|---|---|
Non-selective small molecule inhibitor | ||
Cabozantinib | C28H24FN3O5 | Inhibitor of MET, VEGFR2, and RET kinases |
Crizotinib | C21H22Cl2FN5O | Inhibitor of ALK, HGFR, c-Met, and RON |
Foretinib | C34H34F2N4O6 | ATP-competitive inhibitor of HGFR, VEGFR, MET, and KDR |
Selective small molecule inhibitor | ||
Tivantinib | C23H19N3O2 | Inhibitor of MET, EGFR, InsR, PDGFRα, or FGFR1/4. |
Savolitinib | C17H15N9 | Inhibitor of MET |
Study | Design | Follow-Up (mo) | No. of Patients | Age †, yr | Male Sex | Performance Status * | Intervention | Race | Dosing Schedule (P.O.) |
---|---|---|---|---|---|---|---|---|---|
Choueiri 2013 [38] | Phase II Prospective Cohort | N/A | 74 | 57 | 59 (80%) | 0: 54 (73%) I–II: 20 (27%) | Foretinib; 2w | 64 (86.5%)white 10 (13.5%) nonwhite * | CA: 240 mg days 1–5 CB: 80 mg daily |
Choueiri 2017 [39] | Phase II Prospective cohort | N/A | 109 | 64 | 78 (72%) | 0: 51 (47%) I: 58 (53%) | Savolitinib; 3w | 96 (88%)white 13 (12%) nonwhite * | 600 mg daily |
CREATE 2017 [40] | Prospective cohort | 26.8 | 23 | 62.5 | 20 (87%) | 0: 13 (56.5%) 1: 10 (43.5%) | Crizotinib; 3w | N/A | 250 mg BID |
SWOG 2017 [41] | Phase II RCT (Arm A) | N/A | 25 | 62.1 | 19 (76%) | 0: 12 (48%) I-II:13 (52%) | Tivantinib; 4w | 19 (76%) white 6 (24%) nonwhite * | 360 mg BID |
SWOG 2017 [41] | Phase II RCT (Arm B) | N/A | 25 | 63.6 | 15 (60%) | 0: 9 (36%) I-II: 16 (64%) | Tivantinib + Erlotinib; 4w | 19 (76%) white 6 (24%) nonwhite * | 360 mg BID |
Chanzá 2019 [42] | Retrospective cohort | 11 | 66 | N/A | N/A | 0: 13 (56.5%) I: 10 (43.5%) | Cabozantinib | N/A | 93 (83%) pts: 60 mg daily 19 (17%) pts: started 40 mg daily; 2 pts: increased to 60 mg daily |
SAVOIR 2020 [43] | Phase III RCT | 12 | 33 | 60 | 29 (88%) | 0: 26 (78%) I: 7 (21%) | Savolitinib; 6w (4 tx, 2 none) | 29 (88%) white 4 (12%) nonwhite * | 600 mg daily |
Sumanta 2021 [44] | Phase II RCT (Arm A) | Up to 36 | 44 | 65 | 36 (82%) | 0: 29 (66%) I: 15 (34%) | Cabozantinib; 6w (4 tx, 2 none) | 32 (73%) white 12 (27%) nonwhite * | 60 mg daily |
Sumanta 2021 [44] | Phase II RCT (Arm B) | Up to 36 | 28 | 68 | 22 (79%) | 0: 18 (64%) I: 10 (36%) | Crizotinib; 6w (4 tx, 2 none) | 22 (79%) white 6 (22%) nonwhite * | 250 mg BID |
Sumanta 2021 [44] | Phase II RCT (Arm C) | Up to 36 | 29 | 67 | 19 (66%) | 0: 15 (52%) I: 14 (48%) | Savolitinib; 6w (4 tx, 2 none) | 21 (72%) white 8 (26%) nonwhite * | 600 mg daily |
Tachibana 2022 [45] | Retrospective cohort | 7.1 | 7 | N/A | N/A | N/A | Cabozantinib | N/A | N/A |
CALYPSO 2023 [46] | Phase II Prospective Cohort | N/A | 41 | N/A | N/A | N/A | Savolitinib + Durvalumab | N/A | 600 mg daily |
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Moraes, F.C.A.d.; Vilbert, M.; Alves, V.F.C.; de Oliveira Almeida, G.; Priantti, J.N.; Madeira, T.; Stecca, C.; Fernandes, M.R.; dos Santos, N.P.C. Mesenchymal–Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2023, 24, 17582. https://doi.org/10.3390/ijms242417582
Moraes FCAd, Vilbert M, Alves VFC, de Oliveira Almeida G, Priantti JN, Madeira T, Stecca C, Fernandes MR, dos Santos NPC. Mesenchymal–Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2023; 24(24):17582. https://doi.org/10.3390/ijms242417582
Chicago/Turabian StyleMoraes, Francisco Cezar Aquino de, Maysa Vilbert, Vinícius Freire Costa Alves, Gustavo de Oliveira Almeida, Jonathan N. Priantti, Thiago Madeira, Carlos Stecca, Marianne Rodrigues Fernandes, and Ney Pereira Carneiro dos Santos. 2023. "Mesenchymal–Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 24, no. 24: 17582. https://doi.org/10.3390/ijms242417582