Nivolumab/cabozantinib shows longer lasting health-related quality of life in front-line RCC
Health-related quality of life outcomes were more durable in patients with advanced renal cell carcinoma on nivolumab plus cabozantinib compared to sunitinib.
Nivolumab (Opdivo) plus cabozantinib (Cabometyx) was associated with longer lasting health-related quality of life (HRQOL) compared to sunitinib (Sutent) in patients with advanced renal cell carcinoma, according to a longer follow-up of the CheckMate 9ER trial (NCT03141177).1
During the 32.9 month follow-up, PRO scores revealed that patients receiving nivolumab/cabozantinib maintained or improved HRQoL compared to patients in the sunitinib arm. Longitudinal changes from baseline therefore showed statistical significance (P
The findings, which were presented at the 2022 symposium on genitourinary cancers, demonstrated that this benefit was derived from multiple definitions of deterioration.
During the 151 weeks from baseline, patients receiving nivolumab/cabozantinib had a least squares (LS) mean change of -0.47 from baseline FKSI-19 total score, compared to a decline of -2 .84 compared with those in the sunitinib arm (overall difference in mean change, 2.37; P P <.0001>
Similarly, patients receiving nivolumab/cabozantinib had an EQ-5D-3L health status score of 2.73 versus -0.95 in the sunitinib group (3.68; P = .0001). The EQ-5D-3L UK utility index score demonstrated that patients receiving nivolumab/cabozantinib had a mean LS change from baseline of -0.01 versus -0.06 in the sunitinib arm (0.05; P = .001)
At baseline, both arms demonstrated a high PRO completion rate of at least 90%. At week 151, rates were greater than 75% and 73% in the nivolumab plus cabozantinib and sunitinib arms, respectively. At baseline, both arms had a relatively low symptom burden.
“At nearly 3 years of follow-up, patients continued to report improved HRQoL with nivolumab/cabozantinib compared to sunitinib,” wrote David Cella, FASCO, PhD, of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, and its co-investigators. poster presentation of results. “Treatment with [nivolumab/cabozantinib] was observed to reduce the risk of clinically meaningful deterioration in HRQOL scores compared to sunitinib, regardless of definition of deterioration. »
The CheckMate 9ER trial enrolled 651 patients with advanced RCC who were randomized 1:1 to receive either intravenous nivolumab at a dose of 240 mg intravenously every 2 weeks plus oral cabozantinib 40 mg daily or 50 mg sunitinib orally in 4 weeks – 2 week on/off cycles. Treatment continued until disease progression or unacceptable toxicity occurred.
Patients could not have received nivolumab beyond 2 years from cycle 1; however, they could receive cabozantinib and sunitinib beyond 2 years, provided no disease progression or unacceptable toxicity occurred. If the investigator determined that there might be a benefit, patients could also continue treatment beyond progression.
At an initial follow-up of 18.1 months, nivolumab/cabozantinib was associated with improved progression-free survival (HR, 0.51; 95% CI, 0.41-0.64; P P = 0.001) than sunitinib.2
In this long-term analysis, the FKSI-19 instruments were used to assess disease-related symptoms (DRS) while the EQ-5D-3L visual analogue scale (VAS) was used to assess HRQOL.
FKSI-19 and EQ-5D-3L were administered at baseline, at the start of each treatment cycle (every 2 weeks for nivolumab/cabozantinib and every 6 weeks for sunitinib) and during the following 2 follow-up visits (30 and 100 days since last dose). EQ-5D-3L were also administered every 3 months during survival follow-up. It should be noted that although PRO instruments were more frequently administered in the nivolumab/cabozantinib arm, the current analysis only included assessment time points that were concurrent in both treatment arms.
Investigators noted longitudinal changes from baseline that were assessed via a mixed repeated measures model (MMRM), which adjusted baseline scores and stratification factors, and measured common time points every 6 weeks for 151 weeks. Kaplan-Meier estimates and Cox proportional hazards models were used to perform an analysis of time to first damage (TTFD), confirmed damage (TTCD) and definitive damage (TTDD).
Time to Event Analysis
In this analysis, the TTFD was defined as the time from baseline to the date of the first clinically significant deterioration in PRO scores. TTCD was defined as the time from the date of randomization to the date of the first observed clinically significant deterioration in PRO scores, provided that the deterioration was also confirmed at the next scheduled visit common to both arms or followed by a death or abandonment.
TTDD was defined as the time from the date of randomization to the date of the first observed clinically significant deterioration in PRO scores, provided that this deterioration was observed at all subsequent check-ups or if the patient subsequently defaulted or died .
Nivolumab/cabozantinib treatment induced a significant reduction in TTFD in the FKSI-19 score (HR, 0.71; 95% CI, 0.57-0.87; P = 0.0011), DRS score (HR, 0.70; 95% CI, 0.56-0.87; P = 0.0017), DRS-P score (HR, 0.73; 95% CI, 0.59-0.91; P = 0.0050) and FWB score (HR, 0.69; 95% CI, 0.54-0.87; P = 0.0019).
This benefit was also seen in TTCD in the same scores with FKSI-19 (HR, 0.66; 95% CI, 0.52-0.84; P = 0.0005), DRS (HR, 0.65; 95% CI, 0.50-0.86; P = 0.0020), DRS-P (RR, 0.56; 95% CI, 0.43-0.73; P P = .0045).
Similarly, nivolumab/cabozantinib significantly reduced the risk of TTDD compared to sunitinib in total FKSI-19 (HR, 0.68; 95% CI, 0.52-0.90; P = 0.0070), DRS (HR, 0.53; 95% CI, 0.37-0.75; P = 0.0003) and DRS-P scores (HR, 0.52; 95% CI, 0.38-0.72; P <.0001 the hr for fwb was ci>P = .0003).
Finally, nivolumab/cabozantinib was also associated with significantly reduced deterioration of EQ-5D-3L VAS compared to sunitinib across the TTFD (HR, 0.74; 95% CI, 0.59-0, 92; P = 0.0071), TTCD (HR, 0.74; 95% CI, 0.58-0.95; P = 0.0183) and TTDD (HR, 0.64; 95% CI, 0.48-0.86; P = 0.0026).
Annoying AE Ratings
The impact of treatment-related adverse events (AEs) was also analyzed. The researchers used generalized estimating equation models to descriptively assess the impact of pain with the following ratings:
The impact of treatment-related adverse events (AEs) was also analyzed. The researchers used generalized estimating equation models to descriptively assess the impact of pain with the following ratings: minimal discomfort (not at all? or a little?) or noticeable discomfort (somewhat? a lot? many ?)
This interrogation method is associated with the clinician-assessed measure of AE and is considered a valid form of measurement of treatment-related toxicity, the study authors noted. Additionally, this system has been recommended in the latest version of the FDA oncology guideline.
Overall, patients receiving nivolumab/cabozantinib had fewer troublesome adverse events (AEs) than those receiving sunitinib. Results of a weighted generalized estimating equation revealed that patients in the experimental group were 48% less likely to report bothersome AEs compared to the control group (odds ratio, 0.52; 95% CI, 0. 35-0.77).
“Patients treated with [nivolumab/cabozantinib] showed a decreased risk of being particularly bothered by treatment side effects compared to sunitinib,” the authors concluded. “With the previously reported superior efficacy of [nivolumab/cabozantinib] versus sunitinib, the results show that the additional benefit of improved HRQoL with [nivolumab/cabozantinib] on sunitinib is maintained with longer follow-up.
Cella D, Motzer RJ, Blum S, et al. Health-related quality of life (HRQoL) in patients with previously untreated advanced renal cell carcinoma (aRCC): updated results from the CheckMate 9ER. J Clin Oncol. 2022;40(suppl 6; abstract 323). doi:10.1200/JCO.2022.40.6_suppl.323
Shah AY, Motzer RJ, Apolo AB, et al. Cabozantinib exposure-response analysis for the Phase 3 CheckMate 9ER trial comparing nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. J Clin Oncol. 2021;39(supplement 15):4561. doi:10.1200/JCO.2021.39.15_suppl.4561