First-line ipilimumab plus nivolumab delivers benefits in metastatic renal cell carcinoma

First-line combination immuno-oncology therapy (IO) with ipilimumab and nivolumab provides beneficial effects and has an acceptable safety profile in patients with metastatic renal cell carcinoma, as shown in a Japan study presented at ESMO Asia 2023.

Moreover, “[s]urgical complete response may be achieved with deferred cytoreductive nephrectomy (DCN) after IO combination therapy even in poor-risk patients,” according to the researchers, led by Naoya Nagaya, Urology Department, Juntendo University Graduate School of Medicine, Tokyo, Japan.

However, “there is a possibility that ipilimumab plus nivolumab treatment has weak efficacy for nonclear cell renal cell carcinoma,” they added.

Nagaya and colleagues assessed 30 patients who received ipilimumab plus nivolumab as first-line combination therapy at Juntendo University Hospital. Of these, 27 had real-world inter/poor risk metastatic renal cell carcinoma from January 2019 to August 2023, and three were enrolled in the international phase III study CheckMate-214.

The researchers retrospectively analysed the efficacy of the IO combination therapy in terms of overall survival and safety, primarily through immune-related adverse events (irAEs).

Patients had a median age of 63 years, and 11 out of 30 (37 percent) had prior nephrectomy. The most common metastatic lesion was lung (60 percent), followed by bone (47 percent) and lymph node (37 percent). Of the patients, 18 had intermediate risk, 10 had poor risk, and two had favourable risk. In addition, three were undergoing haemodialysis. [ESMO Asia 2023, abstract 240P]

Twenty-four patients (80 percent) completed four cycles of ipilimumab. The average duration of IO treatment was 15.8 months, while the average duration of response was 27.3 months.

Six patients succumbed to cancer and two from other causes during a mean follow-up of 26.5 months. Among those who died of cancer, four were nonclear cell renal cell carcinoma.

DCN was feasible in two patients with metastatic lesions controlled by IO combination therapy. It was also carried out in another patient who discontinued treatment due to irAE. Surgical complete response was achieved with DCN following IO therapy.

However, seven patients (23 percent) had irAEs leading to treatment discontinuation. Of note, IO therapy could be continued with appropriate hormone replacement in patients with irAEs of endocrine disorders, such as adrenal insufficiency and type 1 diabetes.

“The efficacy of first-line [IO combination therapy] with ipilimumab plus nivolumab in metastatic renal cell carcinoma was demonstrated in the international phase III randomized CheckMate-214 trial,” the researchers said. “We also realized that the prognosis of inter/poor risk metastatic renal cancer could be extended in real clinical practice.”

Risk factors

In another study presented at ESMO Asia 2023, Filipino researchers found that the presence of poor prognostic factors and positive lymph nodes predicted local and distant renal cell carcinoma recurrence. [ESMO Asia 2023, abstract 252P]

This retrospective cohort study included 464 patients who underwent nephrectomy for localized renal cell cancer from January 2017 to December 2021. The most common sites of recurrence were lungs (58.33 percent), lymph nodes (45.83 percent), and bones (20.83 percent).

“A more stringent follow up with appropriate imaging may allow early intervention of metastatic diseases, and possible consideration of lymph node dissection may improve recurrence-free survival,” the investigators said.