Two-year ( 25.4 months minimum; 32.9 months median ) follow-up results from analyses of the phase 3 CheckMate -9ER trial, have demonstrated sustained survival and response rate benefits, as well as health-related quality of life ( HRQoL ) improvements, with the combination of Nivolumab ( Opdivo ) and Cabozantinib ( Cabometyx ) versus Sunitinib ( Sutent ) in the first-line treatment of advanced renal cell carcinoma ( RCC ).
No new safety signals emerged with extended follow-up.
In the full study population:
a) Overall survival ( OS ): At the final overall survival analysis, Nivolumab in combination with Cabozantinib continued to show meaningful improvements in median overall survival ( 37.7 months vs 34.3 months ) and demonstrated a 30% reduction in the risk of death ( hazard ratio, HR=0.70; 95% Confidence Interval [ CI ]: 0.55 to 0.90 ) compared to Sunitinib.
b) Progression free survival ( PFS ): Progression free survival benefits were maintained, with the combination continuing to double median progression free survival versus Sunitinib ( 16.6 months vs 8.3 months, respectively; HR=0.56; 95% CI: 0.46 to 0.68 ).
c) Objective response rate ( ORR ) and Duration of response ( DoR ): Objective response rate benefits were sustained, with nearly twice as many patients responding to Nivolumab in combination with Cabozantinib vs Sunitinib ( 55.7% vs. 28.4% ). Responses were also more durable with the combination, with a median duration of response of 23.1 months, compared to 15.1 months with Sunitinib.
d) Complete response ( CR ): Complete response rates more than doubled among patients treated with the combination, with 12.4% having a complete response vs 5.2% of those treated with Sunitinib.
d) Safety: 97.2% of patients treated with Nivolumab plus Cabozantinib ( n=320 ) experienced a treatment-related adverse event ( TRAE ) of any grade, compared to 93.1% of patients treated with Sunitinib ( n=320 ); 65.0% vs 54.1% had a grade 3 TRAE or more, respectively.
Additionally, in an exploratory analysis of depth of response in target lesions by organ site, a higher percentage of patients experienced any tumor shrinkage benefits with Nivolumab in combination with Cabozantinib versus Sunitinib across lung ( 90.5% vs 76.0% ), lymph node ( 88.4% vs 72.6% ), kidney ( 89.0% vs 71.6% ), liver ( 72.7% vs 53.8% ) and bone ( 85.2% vs 65.0% ) target lesions.
In a separate analysis with 32.9 months median follow-up from the CheckMate -9ER trial, patients continued to report clinically meaningful HRQoL benefits with Nivolumab in combination with Cabozantinib compared to Sunitinib.
HRQoL scores were improved or maintained over time amongst patients treated with the combination, while reductions in scores were observed with Sunitinib.
Additionally, those who received Nivolumab in combination with Cabozantinib were 48% less likely to be notably bothered by treatment side effects than patients in the Sunitinib arm.
These exploratory outcomes were measured using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 ( FKSI-19 ), a quality of life tool specific to kidney cancer, and EQ-5D-3L instruments.
In CheckMate -9ER trial, a total of 651 patients ( 23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 1% or more ) were randomized to receive Nivolumab plus Cabozantinib ( n=323 ) vs Sunitinib ( n=328 ).
Renal cell carcinoma is the most common type of kidney cancer in adults, accounting for more than 431,000 new cases and 179,000 deaths worldwide each year.
Renal cell carcinoma is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe.
The five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 13.9%. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) 2022 Genitourinary Cancers Symposium, 2022