Real-World Study of Nivolumab in RCC Reinforces CheckMate Data

Real-world trial results demonstrated that nivolumab (Opdivo) as a treatment option for patients with advanced renal cell carcinoma (RCC) who received 1 or more prior lines of therapy had comparable overall survival (OS) results with those observed in the phase 3 CheckMate 025 study (NCT01668784), according to data presented at the 35th Annual European Association of Urology Virtual Congress.

“In this interim analysis of the second-line cohort of NORA [NCT02940639], including patients in the real-world setting, similar results were observed with nivolumab after prior therapy compared with the pivotal study,” Marc-Oliver Grimm, MD, said during his presentation of the data. “Clinical benefit was achieved in 57.5% of patients.”

NORA is an ongoing prospective, observational, multicenter, noninterventional study being conducted in Germany. Grimm, from the Department of Urology at Jena University Hospital in Germany, presented the interim analysis results from patients treated with nivolumab with or without ipilimumab (Yervoy) in the real-world setting.

Nivolumab in the Second-Line Setting and Beyond

The median OS for patients treated with nivolumab alone was 26.9 months (95% CI, 16.7-not evaluable [NE]), which is similar to the median OS of 25.8 months (95% CI, 22.2-29.8) observed in CheckMate 025.

Among patients aged 75 or older who received nivolumab as second-line or later therapy, the median OS was NE (95% CI, 12.4-NE). Patients with bone metastases who were given nivolumab in the second-line setting had a median OS of 21.3 months (95% CI, 10.5-NE). Corresponding OS rate estimations at 12 months in the 2 groups were 62.2% and 60.8%.

“Preliminary results demonstrate promising effectiveness in patients 75 years and older and in those with bone metastases,” Grimm said.

Partial response (PR) was the best level of response observed in the trial, which occurred in 63 patients (27%). There were 71 patients (30.5%) who had stable disease following treatment with nivolumab, and 51 patients (21.9%) who had progressive disease. Response data are not yet available or are missing for 48 patients from the interim analysis.

The safety analysis showed that treatment-related adverse effects (TRAEs) occurred in 44.8% of patients who received nivolumab following prior therapy; of those patients, 14.2% had 1 or more grade 3 or greater TRAEs. One death resulted from hepatobiliary failure.

Of the 232 patients enrolled in the study’s monotherapy population, the median age was 71 years (range, 44-86), 66% of whom were aged 65 years or older. The majority of patients were male (72%). The Karnofsky performance scores calculated at baseline were below 70 in 7% of patients, 70 in 8%, 80 in 27%, 90 in 23%, and 100 in 19%. The Memorial Sloan Kettering Cancer Center (MSKCC) risk scores were favorable for 16% of patients, intermediate for 58%, and poor for 13% of patients. The International Metastatic RCC Database Consortium (IMDC) risk score was favorable for 15% of patients, intermediate for 58%, and poor for 17%. Besides patients being of a more advanced age in the NORA trial, baseline characteristics were similar to those in CheckMate 025.

Disease characteristics in those treated with nivolumab monotherapy showed clear-cell RCC in 83% of the monotherapy population and non– clear cell RCC in 17%. The duration of disease at baseline was a mean of 65 months (range, 2-363). The majority of patients in the single-agent cohort (77%) had 1 prior line of therapy, with the remainder (23%) having 2 or more prior lines. The sites of metastasis observed at baseline were lung (71%), bone (32%), liver (27%), adrenal (18%), brain (5%), and other (42%). Eighty-six percent of patients underwent a nephrectomy prior to the study.

Safety of Nivolumab With or Without Ipilimumab

In the group that received the combination of nivolumab and ipilimumab as frontline therapy, 24 out of 62 patients experienced TRAEs. Of those, 45.8% experienced 1 or more grade 3/4 TRAEs. However, no grade 5 TRAEs were observed with the combination.

There were 62 patients who received the combination of nivolumab and ipilimumab who had a median age of 64 years (range, 44-85), and the majority of patients were male (68%). The IMDC risk score was intermediate in 75% of patients and poor in 23%, which closely mirrored the pivotal CheckMate 214 trial (NCT02231749). No patients who received nivolumab plus ipilimumab as front-line therapy had a favorable IMDC or MSKCC risk score. In terms of histologic subtype, 81% of patients had clear cell RCC and 19% had non–clear cell RCC. Thirty percent of patients in the combination cohort had a nephrectomy prior to study treatment.

The investigators led by Grimm concluded that the safety data were consistent with prior pivotal studies in advanced RCC, including both the Checkmate 025 and CheckMate 214 trials.

_Reference

_{Grimm MO, Grünwald V, Von Der Heyde E, Herber M, Müller-Huesmann H, Bedke J. Real world data on the use of nivolumab and ipilimumab combination therapy or nivolumab monotherapy in the treatment of renal cell carcinoma: interim results from the non-interventional study (NIS) NORA. Poster presented at: 35th Annual European Association of Urology Virtual Congress; July 17-26, 2020. Poster 722. bit.ly/2PWYE9M}