ASCO GU 2021: Patient-Reported Outcomes Of Patients With Advanced Renal Cell Carcinoma Treated With First-Line Nivolumab Plus Cabozantinib Versus Sunitinib: The Checkmate 9ER Trial

( The treatment landscape for first-line therapy among patients with metastatic renal cell carcinoma (mRCC) has changed dramatically over the past 2 years. In 2018, publication of the CheckMate214 data demonstrated a survival benefit for patients treated with nivolumab and ipilimumab compared with sunitinib in intermediate and poor-risk mRCC, ushering in the immunotherapy era for mRCC. Subsequent publication of the JAVELIN Renal 101 and KEYNOTE-426 studies in 2019 demonstrated superiority of avelumab and axitinib and pembrolizumab and axitinib, compared to sunitinib in this disease space. These two trials were the first to demonstrate that the combination of immunotherapy with checkpoint inhibition and targeted therapy improved overall survival compared to sunitinib, the previous standard of care. Network meta-analysis following publication of these data demonstrated the apparent superiority of this combined approach. At ESMO 2020, Dr. Choueiri presented first results from the CheckMate-9ER of the combination of nivolumab and cabozantinib, as compared to sunitinib, in the first-line treatment of patients with advanced or metastatic renal cell carcinoma. This first report, which is still unpublished, demonstrated the superiority of nivolumab plus cabozantinib to sunitinib in the first line treatment of patients with advanced renal cell carcinoma with respect to both progression-free survival and overall survival and led to its approval. In a plenary abstract presentation in the Poster Highlights Session: Renal Cell Cancer - Clinical Trial Updates session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Cella presented patient-reported outcomes from this trial.

While previously reported, to briefly summarize, the phase III, open-label CheckMate 9ER trial (NCT03141177) randomized patients with advanced RCC in a 1:1 fashion to receive nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD (N+C; n = 323) or sunitinib (S) 50 mg PO (4 weeks of 6-week cycles; n = 328) in the first-line setting, with randomization stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk score, tumor programmed death ligand 1 expression, geographic region. Treatment was continued until disease progression or unacceptable toxicity.


In this analysis, the authors examined health-related quality of life (HRQoL) patient-reported outcome results, including overall between-group comparisons of treatment groups and time to confirmed deterioration (TCD). Patient reported outcomes were an exploratory endpoint among all randomized patients, as assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) and EQ-5D-3L instruments. These assessments were performed at baseline, at common on-treatment scheduled visits, and at common follow-up visits. 


Changes from baseline were assessed using mixed-model repeated measures (MMRM), adjusting for baseline scores and stratification factors. TCD was calculated from Kaplan–Meier estimates and Cox proportional hazards models.

At the time of data analysis, the median follow-up for overall survival was 18.1 months. Patient reported outcome measures were completed among more than 90% of patients at baseline, and at least 80% of patients at all on-treatment assessments through week 91 in both arms. 

The overall least squares mean difference in change from baseline favored patients treated with nivolumab and cabozantinib, as compared to those receiving sunitinib, as measured with the FKSI-19 (all domains) and with the EQ-5D-3L. 


Patients treated with nivolumab and cabozantinib experienced a lower treatment burden, with decreased risk of confirmed deterioration across most measurements versus sunitinib, including FKSI-19 total, disease-related symptoms (DRS), DRS-physical (DRS-P), DRS-emotional (DRS-E), functional well-being (FWB), and EQ-5D-3L visual analog scale (VAS) scores.


The authors conclude that, in addition to previously presented data demonstrating superiority with respect to progression-free survival and overall survival, patients treated with nivolumab and cabozantinib had statistically significant HRQoL benefits, compared to patients treated with sunitinib. 


Presented by: David Cella, PhD, Professor, Medical Social Sciences; Feinberg School of Medicine
Co-Authors: Toni K. Choueiri, Steven I. Blum, Flavia Ejzykowicz, Melissa Hamilton, Joshua Zhang, Cristina Ivanescu, Robert J. Motzer

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

Related Content: 
ESMO 2020: CheckMate-9ER Study of Nivolumab Combined With Cabozantinib Vs. Sunitinib in Participants With Previously Untreated mRCC - Toni Choueiri
ESMO Virtual Congress 2020: Invited Discussant: First Results From the Randomized Phase 3 CheckMate 9ER Trial
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