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The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice.

ABSTRACT: Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.

SUBMITTER: Raimondi A

PROVIDER: S-EPMC6747319 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice.

Raimondi Alessandra A Randon Giovanni G Sepe Pierangela P Claps Melanie M Verzoni Elena E de Braud Filippo F Procopio Giuseppe G

International journal of molecular sciences 20190830 17

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Theref ...[more]

PMID: 31480348

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Project description:PurposeCirculating tumor DNA (ctDNA) has been validated across multiple indications in the adjuvant and surveillance settings. We evaluated whether targeted digital sequencing (TARDIS) may distinguish a partial response (PR) from a complete response (CR) among patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI) therapy.Materials and methodsEligible patients had mRCC that yielded a PR or CR to ICI therapy. Peripheral blood was obtained at a single time point for ctDNA analysis. TARDIS was used for quantification of average variant allele fractions (VAFs). Our primary objective was to determine the association between VAFs and depth of response (PR v CR). A secondary objective was to determine whether VAFs were associated with disease progression.ResultsTwelve patients were analyzed, nine of whom achieved a PR (75%). Patients received either nivolumab monotherapy (50%) or nivolumab plus ipilimumab (50%). ctDNA analysis incorporated an average of 30 patient-specific mutations (range, 19-35); average coverage depth was 103,342 reads per target. TARDIS quantified a significant difference in VAFs between PR and CR (median, 0.181% [IQR, 0.077%-0.420%] v 0.007% [IQR, 0.0%-0.028%], respectively [P = .014]). Of the 12 patients in the series, six patients demonstrated radiographic progression subsequent to ctDNA assessment. Patients who progressed on subsequent scans had significantly higher ctDNA than those who maintained their response (median, 0.362% [IQR, 0.181%-2.71%] v 0.033% [IQR, 0.007%-0.077%], respectively [P = .026]).ConclusionIn this pilot study, TARDIS accurately differentiated PR from CR among patients with mRCC receiving immunotherapy, and also prospectively identified patients at risk for subsequent progression. Given these findings, we envision subsequent studies that validate these results and investigate the utility of this assay to discern appropriate candidates for discontinuation of immunotherapy.

Dataset Information

The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice.

Publications

The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice.

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