Reference Detail

Ref Type

PMID

Authors

T.K. Choueiri T. Powles M. Burotto M.T. Bourlon B. Zurawski V.M. Oyervides Juárez J.J. Hsieh U. Basso A.Y. Shah C. Suarez A. Hamzaj C.H. Barrios M. Richardet D. Pook Y. Tomita B. Escudier J. Zhang B. Simsek A.B. Apolo R.J. Motzer

Title

Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	31	suppl_4

URL

https://www.annalsofoncology.org/article/S0923-7534(20)42339-7/fulltext

Abstract Text

Background Results from the phase 3 CheckMate 9ER trial evaluating the checkpoint inhibitor (CPI) nivolumab (N) plus the tyrosine kinase inhibitor (TKI) cabozantinib (C) v sunitinib (S) for first-line (1L) treatment of advanced clear cell renal cell carcinoma (aRCC) are reported. As monotherapies, N and C have demonstrated efficacy and a manageable safety profile in aRCC. C has immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining N+C. Methods Patients (pts) were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD v S 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS; a ¼ 0.05 final) by blinded independent central review (BICR). Secondary endpoints (hierarchical testing): overall survival (OS; a ¼ 0.011 first interim analysis), objective response rate (ORR; a ¼ 0.05 final) by BICR, and safety. Results A total of 651 pts (22.6% favorable risk, 57.6% intermediate risk, 19.7% poor risk; 24.9% PD-L1 _1%) were randomized to N+C (n ¼ 323) v S (n ¼ 328). With 18.1 mo median (10.6 mo minimum) study follow-up, all 3 efficacy endpoints were met. N+C significantly improved PFS (HR 0.51 [95% CI 0.41e0.64], P < 0.0001; median, 16.6 v 8.3 mo) and OS (HR 0.60 [98.89% CI 0.40e0.89]; P ¼ 0.0010; medians not reached) v S, and results were consistent across prespecified IMDC risk and PD-L1 subgroups. ORR (95% CI) was significantly higher with N+C v S (55.7% [50.1e61.2] v 27.1% [22.4e32.3]; P < 0.0001), and 8.0% v 4.6% of pts achieved complete response. Median duration of response was 20.2 v 11.5 mo for N+C v S. Any-grade TRAEs occurred in 96.6% v 93.1% of pts treated with N+C v S (60.6% v 50.9% grade _3). One treatment-related death occurred with N+C v 2 with S. TRAEs led to discontinuation of S in 8.8%, N or C in 15.3%, N+C in 3.1%, N only in 5.6%, and C only in 6.6% of pts. Conclusions N+C demonstrated superior PFS, OS, and ORR v S in 1L aRCC. The safety profile of this combination was manageable and consistent with the known singleagent AE profiles of N and C. These results support N+C as a new CPI+TKI option for aRCC pts.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References