Introduction

In CheckMate 9ER, NIVO+CABO improved or maintained HRQoL vs SUN in previously untreated aRCC.

Aim

The objective study is to report an exploratory analysis of HRQoL in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk-based subgroups treated with NIVO+CABO vs SUN in CheckMate 9ER (minimum follow-up, 36.5 mo).

Patient Profile

Adults with previously untreated clear-cell, advanced renal-cell carcinoma. Subgroups were stratified by IMDC categories of favorable (F) risk (score = 0) or intermediate/poor (I/P) risk (score = 1–6) at randomization.

Methods

In this phase 3, randomized, open-label trial

Treatment:

Adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle)

Study Endpoints

HRQoL was evaluated using Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19). Changes from baseline (BL) through wk 151 were analyzed using mixed-model repeated measures (MMRM).

Bother due to treatment side effects (FKSI-19 item GP5) was assessed using a generalized estimating equations model (response dichotomized as minimal [“not at all” or “a little bit”] vs notable [“somewhat,” “quite a bit,” or “very much”]).

Cox proportional hazards (CPH) modeling was used to evaluate time to confirmed deterioration (TTCD).

Results

Differences in least square means (LSM) for FKSI-19 scores through wk 151 indicated HRQoL benefit in the NIVO+CABO arm over the SUN arm for I/P-risk patients (n = 505) but not for F-risk patients (n = 146).

In the I/P-risk subgroup, longitudinal analysis of FKSI-19 total scores indicated that HRQoL improved through wk 151 in the NIVO+CABO arm but decreased from BL in the SUN arm.

HRQoL declined from BL through wk 151 in F-risk patients in the NIVO+CABO and SUN arms.

Patients were less likely to be bothered by side effects of NIVO+CABO vs SUN regardless of risk (I/P-risk odds ratio [OR], 0.50; 95% CI, 0.34–0.75; F-risk OR, 0.51; 95% CI, 0.28–0.91). TTCD analysis of FKSI-19 scores of the I/P-risk subgroup indicated that the NIVO+CABO arm had lower deterioration risk than the SUN arm.

For the F-risk subgroup, risk based on FKSI-19 total scores was similar for both treatment arms.

Table 1: MMRM and CPH analyses of FKSI-19 scores: NIVO+CABO vs SUN

IMDC risk subgroup	FKSI-19 total or subscale	LSM differenceb(95% CI)	Hazard ratio for TTCD (95% CI)
I/P-risk (n = 505)	Total	3.33 (1.96-4.70)	0.58 (0.44-0.76)
	Disease-related symptoms (DRS)	1.59 (1.01-2.18)	0.55 (0.40-0.76)
	DRS-physical (DRS-P)	2.12 (1.27-2.96)	0.51 (0.37-0.70)
	Functional well-being (FWB)	0.54 (0.09-0.98)	0.58 (0.41-0.81)
F-risk (n = 146)	Total	-0.44 (-2.63 to 1.75)	0.99 (0.64-1.54)
	DRS	0.15 (-0.67 to 0.97)	1.09 (0.66-1.82)
	DRS-P	0.04 (-1.21 to 1.30)	0.78 (0.47-1.27)
	FWB	-0.52 (-1.30 to 0.26)	1.03 (0.61-1.73)
aThrough wk 151. bPositive value favors NIVO+CABO over SUN; negative value indicates deterioration.

 

Conclusion

Compared with SUN, NIVO+CABO improved or maintained HRQoL in I/P-risk patients and had less side effect bother in all subgroups. There were no significant differences between treatment arms for F-risk patients.

Reference

J Clin Oncol. 2023 41:16_suppl, 4527-4527