Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: A retrospective analysis

Campbell, Matthew T.; Bilen, Mehmet Asım; Shah, Amishi Yogesh; Lemke, Emily; Jonasch, Eric; Venkatesan, Aradhana M.; Altınmakas, Emre; Duran, Cihan; Msaouel, Pavlos; Tannir, Nizar M.

doi:10.1016/j.ejca.2018.08.014

Cited by 57 publications

(60 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Until further evidence from randomized trials becomes available, our data suggest that nivolumab could be appropriately used alone or in combination with ipilimumab in patients with unclassified histology nccRCC and ccRCC with >20% rhabdoid, based on their approval for second‐line and front line treatment for metastatic RCC respectively. In contrast, clinical trial enrollment or cabozantinib should be considered first for the treatment of patients with papillary type 2 RCC and nivolumab does not appear to have clinical activity for pateints with chromophobe RCC. These findings support the need for randomized trials using blockade of the PD‐1/PD‐L1 pathway in this population, highlighting the ongoing randomized phase II trial comparing the combination of nivolumab with ipilumumab to the current standard of care for previously untreated metastatic nccRCC (NCT03075423).…”

Section: Resultsmentioning

confidence: 98%

“…This was confirmed in the summary cohort pooled analysis, where 20 patients with chromophobe RCC were treated with PD‐1/PD‐L1 without any observed response. Interestingly, a recent retrospective analysis highlighted the potential activity of cabozantinib in patients with chromophobe and papillary type 2 RCC . Therefore, cabozantinib could be an appropriate treatment option for these specific ncc histologies .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

et al. 2019

Self Cite

View full text Add to dashboard Cite

Introduction Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR‐TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non‐clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials. Materials and Methods We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression‐free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta‐analysis of proportions for ORR and disease control rate (DCR). Results Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%–37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%–23.7%) who achieved a complete remission. At a median follow‐up of 24.5 monoths (95% CI, 17.7–32.6), median PFS was 4.9 monoths (95% CI, 3.53–10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment‐related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD‐1/PD‐L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%–26.4%) and 53.4% (95% CI, 44.2%–62.5%). Conclusion Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted. Implications for Practice This article reports on the clinical activity and safety of immune checkpoint inhibitors in non‐clear cell kidney cancer. The retrospective data with the meta‐analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since the data cutoff for this analysis was May 15, 2017, more recently approved drugs for mRCC treatment had been documented for only a few (such as for nivolumab) or for none of the patients with pmRCC (such as for cabozantinib). Recent retrospective data suggest that CPI and cabozantinib might be interesting treatment strategies in nccRCC. Further prospective data are warranted, and some clinical trials are ongoing in this field .…”

Section: Discussionmentioning

confidence: 99%

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC‐Registry

Staehler

Goebell

Müller³

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Non‐clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non‐clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first‐ and second‐line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC‐Registry), 99 patients with papillary mRCC treated with systemic first‐line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first‐line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression‐free survival from start of first‐line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow‐up, and 9% were alive at the end of the individual 3‐year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real‐world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.

show abstract

“…In the first-line subgroup, 23% achieved response, and 82% obtained clinical benefit. Another retrospective study focused on the second and subsequent lines, and showed a median PFS of 8.6, and a median OS of 25.4 months [67]. Finally, real-world data from the Italian Expanded Access Program [68] showed a median SLP of 7.83 months and a 1-year OS of 60%.…”

Section: Non-clear-cell Renal Carcinomamentioning

confidence: 96%

SEOM clinical guideline for treatment of kidney cancer (2019)

et al. 2020

View full text Add to dashboard Cite

In this article, we review de state of the art on the management of renal cell carcinoma (RCC) and provide recommendations on diagnosis and treatment. Recent advances in molecular biology have allowed the subclassification of renal tumours into different histologic variants and may help to identify future prognostic and predictive factors. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. No adjuvant therapy has demonstrated a clear benefit in overall survival. Considering the whole population of patients with advanced disease, the combination of axitinib with either pembrolizumab or avelumab increase response rate and progression-free survival, compared to sunitinib, but a longer overall survival has only been demonstrated so far with the pembrolizumab combo. For patients with IMDC intermediate and poor prognosis, nephrectomy should not be considered mandatory. In this subpopulation, the combination of ipilimumab and nivolumab has also demonstrated a superior response rate and overall survival vs. sunitinib. In patients progressing to one or two antiangiogenic tyrosine-kinase inhibitors, both nivolumab and cabozantinib in monotherapy have shown benefit in overall survival compared to everolimus. Although no clear sequence can be recommended, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in patients with metastatic RCC.

show abstract

Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: A retrospective analysis

Cited by 57 publications

References 21 publications

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC‐Registry

SEOM clinical guideline for treatment of kidney cancer (2019)

Contact Info

Product

Resources

About