The combination significantly improved progression-free and overall survival compared with sunitinib in frontline renal cell carcinoma.
Combination therapy with nivolumab (Opdivo) and cabozantinib (Cabometyx) significantly improved progression-free and overall survival compared with sunitinib (Sutent) as frontline treatment for patients with advanced renal cell carcinoma (RCC), according to findings from the phase 3 CheckMate-9ER trial.1
Data from the trial presented at the 2020 ESMO Virtual Congress showed that the immunotherapy/TKI regimen reduced the risk of disease progression or death by 49% versus sunitinib, with a median progression-free survival (PFS) of 16.6 months versus 8.3 months, respectively (HR, 0.51; P <.0001). The median follow-up time was 18.1 months.
Additional results showed that the median overall survival (OS) was not reached in either arm, and there was a 40% reduction in the risk of death with the combination (HR, 0.60; P = .0010).
“With expanding options for patients with advanced RCC, the overall efficacy, safety, and quality of life benefits, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” lead study author Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, senior physician with Dana-Farber Cancer Institute, and the Jerome and Nancy Kohlberg Chair and professor of medicine with Harvard Medical School, said in a press conference during the congress. “These results, we believe, support nivolumab and cabozantinib as a potential first-line option in patients with advanced renal cell carcinoma.”
In the international, randomized, phase 3 CheckMate-9ER trial, 651 patients with advanced RCC received the combination of nivolumab and cabozantinib (n = 323) or sunitinib (n = 328) in the first-line setting. Patients must have had previously untreated advanced or metastatic disease, a clear cell component, and any International Metastatic RCC Database Consortium (IMDC) risk score.
The combination demonstrated a benefit across numerous subgroups, including age, sex, PD-L1 expression, bone metastases, IMDC risk group, and geographic region.
The objective response rate (ORR0 was also doubled with nivolumab/cabozantinib in this setting compared with sunitinib, at 55.7% versus 27.1%, respectively (P <.0001). In the combination arm, the complete response (CR) rate was 8.0%, the partial response (PR) rate was 47.7%, and the stable disease (SD) rate was 32.2%. Additionally, 5.6% of patients had progressive disease (PD) and 6.5% were not evaluable or not assessed. In the sunitinib arm, the CR, PR, and SD rates were 4.6%, 22.6%, and 42.1%, respectively. Moreover, 13.7% of patients had PD and 17.1% of patients were not evaluable or not assessed.
Regarding safety, the incidence of the most common, any-grade and high-grade treatment-related adverse events (TRAEs) were similar in both arms. More than 50% of patients on the combination required dose reductions of cabozantinib due to adverse effects (AEs). TRAEs led to treatment discontinuations in 15.3% of those in the nivolumab/cabozantinib arm and in 8.8% of those on sunitinib. Specifically, 3.1% of patients discontinued both nivolumab and cabozantinib due to AEs, 5.6% discontinued only nivolumab, and 6.6% discontinued only cabozantinib.
The overall rate of serious AEs was similar between the 2 groups; however, liver toxicity was more common with cabozantinib/nivolumab. Nineteen percent of patients on the combination required corticosteroids due to immune-related AEs, 4% of whom needed corticosteroids for at least 30 days.
Beyond improved treatment response and survival benefits, the combination was found to provide an improved HRQoL compared with sunitinib. HRQoL was maintained over time with nivolumab/cabozantinib versus sunitinib, which had a consistent deterioration per Functional Assessment of Cancer Therapy- Kidney Symptom Index (FKSI)-19 total score. The between-arm differences were significant at nearly all time points.
Disease-related symptoms (DRS) also improved with nivolumab/cabozantinib. Those who received sunitinib experienced a decline per FKSI-Disease-DRS.
Both nivolumab and cabozantinib are currently approved in separate indications in RCC. In April 2018, the FDA approved nivolumab plus ipilimumab (Yervoy) as a frontline treatment for intermediate- and poor-risk patients with advanced RCC. Prior to that, in 2015, the PD-1 inhibitor was approved for use as a single agent in the treatment for patients with metastatic RCC following prior antiangiogenic therapy. In 2017, cabozantinib was approved by the FDA for use in previously untreated patients with advanced RCC and was initially approved as a treatment for those who had progressed on 1 prior antiangiogenic treatment.
1. Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Ann Oncol. 2020;31(4). Abstract 696O.