Nivolumab + cabozantinib combo offers better QoL in advanced RCC

First-line treatment with nivolumab plus cabozantinib (NIVO+CABO) led to significantly better patient-reported quality of life (QoL) outcomes compared with sunitinib in patients with advanced renal cell carcinoma (RCC), according to an exploratory analysis of the CheckMate 9ER* trial presented at ASCO GU 2021.

This phase III, open-label trial evaluated 651 patients with advanced RCC who were randomly assigned to receive either intravenous NIVO 240 mg every 2 weeks + oral CABO 40 mg once/day (n=323) or oral sunitinib 50 mg once/day (n=328) on 4-weeks-on, 2-weeks-off cycles. Patients continued treatment until disease progression or unacceptable toxicity. Health-related QoL was assessed using FKSI-19** and EQ-5D-3L*** patient-reported outcome (PRO) instruments, with completion rates of >90 percent at baseline and ≥80 percent through week 91. [ASCO GU 2021, abstract 285]

At week 91, patients who received NIVO+CABO had significantly greater improvements in FKSI-19 total and disease-related symptom (DSR) scores from baseline, indicating better QoL, compared with those who received sunitinib (overall difference in mean change, 2.90 and 1.55, respectively; p<0.0001 for both).

Similarly, those on NIVO+CABO achieved significant improvements in EQ-5D-3L utility index and VAS scores from baseline to week 91 than those on sunitinib (overall difference in mean change, 0.05; p=0.0005 and 3.26; p=0.0011, respectively).

Patients in the NIVO+CABO arm demonstrated a significantly reduced risk of confirmed deterioration as per total FKSI-19 score (hazard ratio [HR], 0.64; p=0.0003) and FKSI-19 DRS score (HR, 0.62; p=0.0006) than those in the sunitinib arm.

A significantly reduced risk of confirmed deterioration was also observed in other FKSI domains, such as DRS-physical, DRS-emotional, and functional well-being (HR, 0.53, 0.65, and 0.67, respectively; p<0.01 for all), but not the treatment side effect domain (HR, 0.90).

Moreover, patients in the NIVO+CABO arm experienced greater reductions in the risks of confirmed deterioration in the EQ-5D-3L VAS⁺ and utility index scores (HR, 0.71 and 0.78, respectively) compared with those in the sunitinib arm.

However, caution is needed when interpreting these findings, said study author Dr David Cella from the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois, US.  “[As we] assessed PROs directly after the 2-week treatment-free period for patients in the sunitinib arm, we might be underestimating the impact of sunitinib on patients’ QoL,” he said.

“[Nevertheless,] this analysis showed that NIVO+CABO provides QoL benefits over sunitinib, … [and demonstrates] a delay in deterioration and a significantly decreased risk of confirmed deterioration in QoL scores,” said Cella.

“These results indicate that the superior clinical efficacy of NIVO+CABO [over sunitinib] is accompanied by the additional benefit of better QoL [outcomes], … [which] also support the acceptable tolerability profile of the NIVO+CABO combination for patients with advanced RCC,” he noted.

*CheckMate 9ER: A Study of nivolumab combined with cabozantinib compared to sunitinib in previously untreated advanced or metastatic renal cell carcinoma

**FKSI-19: Functional Assessment of Cancer Therapy-Kidney Symptom Index

***EQ-5D-3L: Three-level version of the EQ-5D

⁺VAS: Visual analogue scale