TY - JOUR
T1 - Current evidence for second-line treatment in metastatic renal cell carcinoma after progression to immune-based combinations
AU - Iacovelli, Roberto
AU - Ciccarese, Chiara
AU - Procopio, Giuseppe
AU - Astore, Serena
AU - Cannella, Maria Antonella
AU - Maratta, Maria Grazia
AU - Rizzo, Mimma
AU - Verzoni, Elena
AU - Porta, Camillo
AU - Tortora, Giampaolo
PY - 2022
Y1 - 2022
N2 - The recent approval of immune checkpoint inhibitor (ICI)-based combinations has redefined the first-line standard of care of metastatic renal cell carcinoma (mRCC) patients. Although the undisputed advantage of these combinations, most patients progressed, requiring subsequent therapies. The change of first-line therapy inevitably led to modification of the all mRCC treatment algorithm; to date, the most appropriate second-line options remain still unclear. The aim of our review was to provide a useful summary of the available evidence in order to overcome the doubts about treatment sequences. Retrospectively, the efficacy of second-line VEGFR-TKIs seems to be greater after failure of a dual ICIs combination rather than after ICIs plus VEGFR-TKIs, nevertheless prospective data of second-line TKIs are limited. Moreover, ICI re-challenge could be an option but, again, most data derived from retrospective series emphasizing the identification of predictive factors of response to select mRCC patients that could benefit from this strategy. Novel molecules and different ICI-based combinations are under evaluation with the aim of implementing the second-line setting. In particular, belzutifan, ciforadenant (CPI-444), and talazoparib achieved encouraging objective response rates (ORR) in phase I/II trials. Phase III trials comparing these new molecules with the standard of care are currently ongoing. The first-line regimen, and the type and duration of response emerged as crucial factors that could influence the efficacy of second-line therapy. Prognostic models that integrate clinical features and molecular biomarkers with a predictive value are warranted to guide clinicians in the decision-making process with the ultimate goal of offering to the patients the most effective therapy in a personalized, precision medicine-based, therapeutic strategy.
AB - The recent approval of immune checkpoint inhibitor (ICI)-based combinations has redefined the first-line standard of care of metastatic renal cell carcinoma (mRCC) patients. Although the undisputed advantage of these combinations, most patients progressed, requiring subsequent therapies. The change of first-line therapy inevitably led to modification of the all mRCC treatment algorithm; to date, the most appropriate second-line options remain still unclear. The aim of our review was to provide a useful summary of the available evidence in order to overcome the doubts about treatment sequences. Retrospectively, the efficacy of second-line VEGFR-TKIs seems to be greater after failure of a dual ICIs combination rather than after ICIs plus VEGFR-TKIs, nevertheless prospective data of second-line TKIs are limited. Moreover, ICI re-challenge could be an option but, again, most data derived from retrospective series emphasizing the identification of predictive factors of response to select mRCC patients that could benefit from this strategy. Novel molecules and different ICI-based combinations are under evaluation with the aim of implementing the second-line setting. In particular, belzutifan, ciforadenant (CPI-444), and talazoparib achieved encouraging objective response rates (ORR) in phase I/II trials. Phase III trials comparing these new molecules with the standard of care are currently ongoing. The first-line regimen, and the type and duration of response emerged as crucial factors that could influence the efficacy of second-line therapy. Prognostic models that integrate clinical features and molecular biomarkers with a predictive value are warranted to guide clinicians in the decision-making process with the ultimate goal of offering to the patients the most effective therapy in a personalized, precision medicine-based, therapeutic strategy.
KW - Immune-based combinations
KW - Novel agents
KW - mRCC
KW - Second-line
KW - Renal cell carcinoma
KW - Immune-based combinations
KW - Novel agents
KW - mRCC
KW - Second-line
KW - Renal cell carcinoma
UR - http://hdl.handle.net/10807/305280
U2 - 10.1016/j.ctrv.2022.102379
DO - 10.1016/j.ctrv.2022.102379
M3 - Article
SN - 0305-7372
VL - 105
SP - N/A-N/A
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
ER -