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 carcinoma^a

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 score^b	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 evaluation^d)
ESMO-MCBS score^b	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 score^b	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 score^b	4^e (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 months^f
HR (95% CI)	OS HR: 0.66 (0.54– 0.80)
QoL/toxicity	QoL benefit reported in exploratory evaluation^d
ESMO-MCBS score^b	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 score^b	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 score^b	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

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Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373:1803-1813.
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.
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.
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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.
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.
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.
Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340–2366.