Biomarkers in renal cell carcinoma: Towards a more selective immune checkpoint inhibition

Sarkis, Julien; Assaf, Joy; Alkassis, Marwan

doi:10.1016/j.tranon.2021.101071

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…This finding is consistent with our results from the PRISM database but different from previous findings of PD-1 receptor internalization after nivolumab treatment. The impact of the overexpression of PD-1 on RCC still needs further investigation [12,13]. Previous studies have focused on programmed death-ligand 1 (PD-L1), with high levels of PD-L1 expression being reported in the high-risk RCC group [14].…”

Section: Discussionmentioning

confidence: 99%

Axitinib Rechallenge Restores the Anticancer Effect after Nivolumab: A Case Report

Chang,

Wang

et al. 2023

IJMS

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The immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combination treatment is currently the first-line treatment for metastatic renal cell carcinoma (mRCC). However, its efficacy beyond the third-line setting is expected to be relatively poor, and high-grade toxicities can develop by prior exposure to multiple drugs, resulting in a relatively poor performance in patients. Determining the best treatment regimen and sequence remains difficult and requires further investigation in patients with mRCC. In this study, two cases of mRCC, who failed several lines of TKI and nivolumab but exhibited a good anticancer effect after rechallenging with axitinib, are described. Both patients had a faster time to best response and better progression-free survival (PFS) than during previous treatments. Moreover, the axitinib dose could be reduced to 2.5 mg daily when used in combination with nivolumab while continuing to exert an impressive anticancer effect. To determine the cytotoxic effect, we performed a lymphocyte activation test and found that the level of granzyme B released by cytotoxic T lymphocytes and natural killer cells was higher when axitinib was combined with nivolumab. To evaluate this result, a bioinformatics approach was used to analyze the PRISM database. In conclusion, based on the results of a lymphocyte activation test and PD-1 expression, our findings indicate that sequential therapy with axitinib rechallenge after nivolumab resistance is reasonable for the treatment of mRCC.

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Section: Discussionmentioning

confidence: 99%

Axitinib Rechallenge Restores the Anticancer Effect after Nivolumab: A Case Report

Chang,

Wang

et al. 2023

IJMS

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“…There are certainly differences between axitinib, lenvatinib, and cabozantinib based on targets and further investigation into IO/TKI synergism and angiogenesis signatures may enable clinically impactful biomarker development in this space. Further, investigators are assessing alternative biomarkers for response to PD-1/PD-L1 therapy, although these remain grossly inconsistent and not relevant for clinical practice quite yet [ 78 ].…”

Section: Ongoing Areas Of Study Within the Front-line Treatment Paradigmmentioning

confidence: 99%

Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma

Zarrabi

Lanade

Geynisman

2022

Cancers

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The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development of biomarkers will certainly assist in this setting, and validation of predictive markers represents an unmet need. In their absence, we highlight features of disease and nuances to datasets from landmark prospective clinical trials to help inform treatment selection. There is growing evidence to support deferring upfront systemic therapy in some patients, with opportunities for active surveillance or metastasis-directed therapy. In others, upfront systemic therapy is warranted and necessitates thoughtful consideration of multiple clinicopathologic parameters to inform optimal patient-centered decision making.

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“…To date, only mismatch repair deficiency, microsatellite instability and neutrophile to lymphocyte ratio (NLR) were reported to anticipate efficacy of immunotherapy. 9 Additional clinical trials on the use of circulating tumor DNA (ctDNA), loss of Polybromo-1 (PBRM-1) and T cell immunoglobulin and mucin domain-3 (TIM-3) are needed to test the responsiveness to immune treatment. 10 In the same line of ideas, researchers are exploring the association of multiple serum markers such as soluble VEGF, circulating microRNAs, carbonic anhydrase 9 and inflammatory markers (IL-6 and IL-8) with treatment results with several TKIs.…”

mentioning

confidence: 99%

The nivolumab/cabozantinib combination and the future of doublets in advanced renal cell cancer treatment

Lilly

Sarkis

2021

J Oncol Pharm Pract

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Biomarkers in renal cell carcinoma: Towards a more selective immune checkpoint inhibition

Cited by 5 publications

References 10 publications

Axitinib Rechallenge Restores the Anticancer Effect after Nivolumab: A Case Report

Axitinib Rechallenge Restores the Anticancer Effect after Nivolumab: A Case Report

Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma

The nivolumab/cabozantinib combination and the future of doublets in advanced renal cell cancer treatment

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