HRQoL Proves to Be Helpful Prognostic Factor for Cabozantinib/Nivolumab in Advanced RCC

David Cella, MD

Higher baseline and longitudinal evaluations of health-related quality of life (HRQoL) prior to and during treatment with nivolumab (Opdivo) and cabozantinib (Cabometyx) demonstrated an association with improved progression-free survival (PFS) and overall survival (OS) in patients with advanced, treatment-naïve renal cell carcinoma (RCC), according to findings from an exploratory analysis of the phase 3 CheckMate 9ER trial (NCT03141177) presented at the 2022 ESMO Congress.¹

In the baseline model, the Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 (FKSI-19) total evaluation highlighted a strong association between higher HRQoL score and lower risk of progression or death (HR for PFS, 0.85; 95% CI, 0.81-0.89; P < .0001) and death alone (HR for OS, 0.78; 95% CI, 0.73-0.82; P < .0001).

In the longitudinal model, the FKSI-19 total assessment revealed a similar association for PFS (HR, 0.89; 95% CI, 0.84-0.95; P = .0002) and OS (HR, 0.69; 95% CI, 0.64-0.75; P < .0001).

“This exploratory research, based on data from the CheckMate 9ER trial, shows that baseline HRQoL is a prognostic factor for both PFS and OS in patients with advanced RCC, and that improvements in HRQoL can be of prognostic value for PFS and OS along the course of treatment and study, as previously demonstrated in an exploratory analysis of HRQoL data from the phase 3 CheckMate 214 trial [NCT02231749],” lead study author David Cella, MD, director of the Institute for Public Health and Medicine in the Center for Patient-Centered Outcomes at Northwestern Medicine, and coauthors wrote in the poster.

The CheckMate 9ER trial enrolled patients with treatment-naïve, clear cell advanced RCC with measurable disease according to RECIST v1.1 criteria and a Karnofsky performance status score of at least 70.

Patients were randomly assigned 1:1 to 240 mg of intravenous nivolumab every 2 weeks plus 40 mg of oral cabozantinib once daily or 50 mg of oral sunitinib (Sutent) once daily for 4 weeks on and 2 weeks off.

The combination received FDA approval in January 2021 after demonstrating a 49% reduction in the risk of disease progression or death, an improvement in OS, and a doubling in the objective response rate compared with sunitinib as first-line therapy in CheckMate 9ER.²

HRQoL measured using the FKSI-19 and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) instruments served as an exploratory end point of the trial. Findings from the primary analysis of the study showed that HRQoL outcomes evaluated from baseline to week 115 favored the use of cabozantinib and nivolumab compared with sunitinib. Moreover, the combination was associated with a reduction in the risk of clinically meaningful deterioration in HRQoL.

As such, investigators set out to determine the association between HRQoL and clinical outcomes in this population.

Most patients in the combination and monotherapy arms completed the FKSI-19 assessment at baseline (≥93%). The mean FKSI-19 scores at baseline in the combination arm were comparable to those of healthy patients, indicating a relatively low symptom burden at baseline.

Additional results indicated that the association between higher HRQoL scores and reduced risk of progression or death was apparent for each of the analyzed FKSI-19 scores for both PFS and OS.

Baseline Model:

FKSI-19 disease-related symptoms (DRS): (HR for PFS, 0.85; 95% CI, 0.80-0.90; P < .0001); (HR for OS, 0.76; 95% CI, 0.71-0.82; P < .0001)

FKSI-19 DRS-physical (DRS-P): (HR for PFS, 0.85; 95% CI, 0.80-0.91; P < .0001); (HR for OS, 0.76; 95% CI, 0.71-0.82; P < .0001)

FKSI-19 functional well-being (FWB): (HR for PFS, 0.80; 95% CI, 0.74-0.87; P < .0001); (HR for OS, 0.68; 95% CI, 95% CI, 0.61-0.76; P < .0001)

Longitudinal Model:

FKSI-19 DRS: (HR for PFS, 0.85; 95% CI, 0.79-0.92; P < .0001); (HR for OS, 0.66; 95% CI, 0.61-0.72; P < .0001)

FKSI-19 DRS-P: (HR for PFS, 0.83; 95% CI, 0.77-0.89; P < .0001); (HR for OS, 0.64; 95% CI, 0.58-0.70; P < .0001)

FKSI-19 FWB: (HR for PFS, 0.86; 95% CI, 0.77-0.96; P = .0059); (HR for OS, 0.51; 95% CI, 0.42-0.61; P < .0001)

“In the future, these associations between HRQoL and clinical outcomes may have the potential to influence the treatment approaches adopted by clinicians for patients with advanced RCC. Additional studies are needed to validate these observations and to demonstrate that therapy selection based on these variables is beneficial for patients,” the authors concluded.

References

1. Cella D, Porta C, Hamilton M, et al. Association between health-related quality of life and clinical outcomes in patients with advanced first-line renal cell carcinoma: exploratory analyses from CheckMate 9ER. Ann Oncol. 2022;33(suppl 7):S660-S680. doi:10.1016/annonc/annonc1072
2. FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. News release. FDA. January 22, 2021. Accessed September 14, 2022. http://bit.ly/2Mjrt1i.