The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma

Calvo, Emiliano; Porta, C.; Grünwald, Viktor; Escudier, Bernard

doi:10.1634/theoncologist.2018-0267

Cited by 35 publications

(30 citation statements)

References 90 publications

(186 reference statements)

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“…The treatment landscape for mRCC has transformed and will continue to do so rapidly given the ongoing trials for first-line treatment and the integration of immune checkpoint inhibitors [14]. The IMDC risk group classification is relevant for clinicians, as treatments are often approved for patients in a particular risk group [15,16].…”

Section: Discussionmentioning

confidence: 99%

“…For patients classified as intermediate or poor risk, nivolumab plus ipilimumab was approved for first-line treatment. Axitinib, although it is not an approved first-line treatment option, is recommended by the National Cancer Center Network (NCCN) as a treatment option (category 2A) [14]. For patients in all risk groups, the U.S. Food and Drug Administration recently approved two combinations, pembrolizumab plus axitinib and avelumab plus axitinib, as first-line treatment based on improved OS, PFS, and ORR relative to patients treated with sunitinib in the KEYNOTE-426 and JAVELIN Renal 101 trials, respectively [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

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Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group

et al. 2020

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Background. International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment. Materials and Methods. Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors. Results. Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors. Conclusion. This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes. The Oncologist 2020;25:422-430Implications for Practice: This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4-61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group

et al. 2020

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“…The success indicated by these studies led to the recent approval of Nivolumab, which proved better in improving overall-survival and also was better tolerated when compared to everolimus in VEGF-refractory patients [86]. Moreover, the combination of Nivolumab with Ipilimumab for patients with intermediate or poor risk disease was also approved, again showing the value of combining blocking of several immune checkpoints [87,88]. Nowadays, one of the major challenges is proper selection of the patients that will experience the maximum benefit; this assessment depends on factors such as performance status of the patient and prognostic risk stratification, and there is no accurate (Level I evidence) biomarker for tailoring treatment in the clinic [89].…”

Section: Immune Therapies -Brief Overview In Kidney Cancermentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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“…Based on encouraging data from a phase III trial on metastatic melanoma, the first CTLA-4 checkpoint inhibitor, ipilimumab, was approved by the Food and Drug Administration (FDA) in 2011 [4]. Despite being approved for only unresectable or metastatic melanoma, ipilimumab can be viewed as a promising therapeutic strategy for many cancer types, such as renal cell carcinoma (RCC) [5], non-small cell lung carcinoma (NSCLC) [6] and small cell lung cancer (SCLC).…”

Section: Introductionmentioning

confidence: 99%

Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China

Zhang

Song

et al. 2020

BMC Cancer

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Background: The purpose of the present study was to obtain information on the use of PD-1/PD-L1 inhibitors by oncologists in China through a national questionnaire survey. Methods: Between the 7th and 25th of July in 2019, a questionnaire designed by the Chinese Society of Clinical Oncology Immuno-Oncology (CSCO IO) Committee on the current status of the use of PD-1/PD-L1 inhibitors was distributed online and offline to cancer-related medical departments in thirty different provinces and autonomous regions of China. The national questionnaire consisted of three sections as follows: general information, current status of the application of PD-1/PD-L1 inhibitors in the clinic, and oncologists' concerns regarding utilization. Results: The valid response rate of the current status survey was 76.3%. The proportion of senior doctors (physician-in-charge or a more superior position for more than 3 years) among the respondents was relatively high (67.0% in 588). Of the respondents, 59.2% had prescribed PD-1/PD-L1 inhibitors during clinical treatment, and the most frequent reason for not prescribing these inhibitors was the choice "do not understand the mechanism and the efficacy of PD-1/PD-L1 inhibitors". In addition, 77.9% of the prescribers used the medications in an off-label situation, and the most important motivation for this use was the fact that "there were indications abroad but not domestically". In addition, 77.9% of the prescribers believed that "immunotherapy-related adverse effects could be controlled or intervened through follow-up management". The prescribers were mostly concerned about "how to identify pseudoprogression and hyperprogression" and "immunity-related adverse effects management". Conclusion: The present study highlights the current status of PD-1/PD-L1 inhibitors in China. Increasing numbers of medical oncologists are interested in PD-1/PD-L1 inhibitors, and they are in need of immunotherapy education.

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The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma

Cited by 35 publications

References 90 publications

Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group

Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China

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