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eUpdate – Renal Cell Carcinoma Treatment Recommendations 2

eUpdate – Renal Cell Carcinoma Treatment Recommendations

Published: 26 February 2020. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the Renal Cell Carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Escudier B, Porta C, Schmidinger M et al. Ann Oncol 2019; 30(5): 706–720.

Section

Table 7: ESMO-MCBS table for new therapies/indications in renal cell carcinomaa

The following Table replaces Table 7.

Therapy

Pembrolizumab in combination with axitinib

Disease setting

Previously untreated advanced renal cell carcinoma

Trial

Study to evaluate the efficacy and safety of pembrolizumab in combination with axitinib versus sunitinib monotherapy in participants with renal cell carcinoma (KEYNOTE-426) [1]

NCT02853331

Phase

Phase III

Control

Sunitinib

PFS 11.1 months

12 months survival 78%

Absolute survival gain

PFS gain 4 months

12 months survival gain: 12%

HR (95% CI)

PFS HR 0.69 (0.57-0.84)

OS HR: 0.53 (0.38-0.74)c significant

QoL/toxicity

 -

ESMO-MCBS scoreb

4 (Form 2b)

Therapy

Nivolumab, a PD-1 checkpoint inhibitor

Disease setting

Advanced clear cell renal cell carcinoma previously treated with one or two regimens of anti-angiogenic therapy

Trial

Study of nivolumab vs. everolimus in pre-treated advanced or metastatic clear-cell renal cell carcinoma  

(CheckMate 025) [2] 

NCT01668784 

Phase

Phase III 

Control

Everolimus 

Median OS: 19.6 months 

Absolute survival gain

OS gain: 5.4 months 

HR (95% CI)

OS HR: 0.73 (0.57–0.93) 

QoL/toxicity

Improved toxicity profile (QoL benefit reported in exploratory evaluationd)

ESMO-MCBS scoreb

5 (Form 2a) 

 

Therapy

Cabozantinib

Disease setting

Advanced renal cell carcinoma in adults following prior vascular endothelial growth factor receptor tyrosine kinase inhibitors 

Trial

A study of cabozantinib (XL184) vs everolimus in subjects with metastatic renal cell carcinoma (METEOR) [3]  

NCT01865747 

Phase

Phase III 

Control

Everolimus 

Median OS: 16.5 months 

Absolute survival gain

OS gain:  

4.9 months 

HR (95% CI)

OS HR: 0.66 (0.53–0.83) 

QoL/toxicity

-

ESMO-MCBS scoreb

3 (Form 2a) 

 

Therapy

Lenvatinib in combination with everolimus

Disease setting

Advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy 

Trial

A study of E7080 alone, and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor (VEGF)-targeted treatment [4] 

NCT01136733 

Phase

Phase II 

Control

Everolimus 

Median OS: 15.4 months 

Absolute survival gain

OS gain: 

10.1 months 

HR (95% CI)

OS HR: 0.51 (0.30–0.88) 

QoL/toxicity

-

ESMO-MCBS scoreb

4e (Form 2a) (secondary endpoint of OS in a small phase II randomised study) 

 

Therapy

Nivolumab in combination with ipilimumab

Disease setting

First-line therapy for intermediate- and poor-risk advanced metastatic renal cell carcinoma 

Trial

Nivolumab combined with ipilimumab versus sunitinib in previously untreated advanced or metastatic renal cell carcinoma (CheckMate 214) [5,6,7] 

NCT02231749 

Phase

Phase III 

Control

Sunitinib 

Median OS: 26.6 months 

Absolute survival gain

OS gain:

13 monthsf

HR (95% CI)

OS HR: 0.66 (0.54– 0.80)

QoL/toxicity

QoL benefit reported in exploratory evaluationd

ESMO-MCBS scoreb

4 (Form 2a)

 

Therapy

Tivozanib

Disease setting

Recurrent or metastatic renal cell carcinoma with clear cell component, and prior nephrectomy 

Trial

A study to compare tivozanib (AV-951) to sorafenib in subjects with advanced renal cell carcinoma (TIVO-1) [8] 

NCT01030783 

Phase

Phase III 

Control

Sorafenib 

Median PFS: 9.1 months 

Absolute survival gain

PFS gain: 2.8 months 

HR (95% CI)

PFS HR: 0.80 (0.64–0.99) 

QoL/toxicity

OS NS 

No QoL benefit 

ESMO-MCBS scoreb

1 (Form 2b) 

 

Therapy

Avelumab in combination with axitinib

Disease setting

Previously untreated advanced renal cell carcinoma

Trial

A study of avelumab with axitinib versus sunitinib in advanced renal-cell carcinoma (JAVELIN Renal 101) [9]

Phase III

NCT02684006

Phase

Phase III

Control

Sunitinib

PFS 8.4 months

Absolute survival gain

ITT PFS gain 5.4 months

HR (95% CI)

ITT PFS HR 0.69 (0.56-0.84)

QoL/toxicity

 -

ESMO-MCBS scoreb

3 (Form 2b)

aEMA approvals since January 2016. 

bESMO-MCBS version 1.1 [10]. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee.  

cInterim analysis of survival met predefined threshold of P<0.0001 but OS not mature

dNot eligible for QoL adjustment

erandomised phase II trial, no confirmatory phase III data

fCalculated conservative estimate of gain based on PE HR 0.66

CI, confidence interval; EMA, European Medicines Agency; ESMO-MCBS, ESMO-Magnitude of Clinical Benefit Scale; HR, hazard ratio; ITT, intention to treat; NS, not significant; OS, overall survival; PD-1, programmed cell death protein 1; PE, primary efficacy; PFS, progression-free survival; QoL, quality of life. 

Section

References

  1. Rini BI, Plimack ER, Stus V, et al; KEYNOTE-426 Investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019; 380:1116-1127
  2. Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373:1803-1813. 
  3. Choueiri TK, Escudier B, Powles T et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol 2016; 17:917-927. 
  4. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 2015; 16: 1473-1482. 
  5. Motzer R J, Tannir N M, McDermott D F et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378(14):1277-1290. 
  6. Motzer R J, Rini B I, McDermott D F et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet 2019; 20(10):1370-1385.
  7. Cella D, Grünwald V, Escudier B et al. Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol 2019; S1470-2045(18)30778-2. 
  8. Motzer RJ, Nosov D, Eisen T et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol 2013;31:3791-3799. 
  9. Motzer, RJ, Penkov K, Haanen J et al; Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019; 380:1103-1115.
  10. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340–2366.

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