Advanced RCC Can Still Respond to Nivolumab After Initial Progression

A subset of patients with advanced renal cell carcinoma (RCC) experienced a reduction in tumor size after undergoing postprogression treatment with nivolumab, according to results from CheckMate 025 published in European Urology.

“This observation supports the use of nivolumab beyond progression in patients with symptomatic improvement despite progressive disease,” wrote researcher Bernard Escudier, MD, of Gustave Roussy in Villejuif, France, and colleagues. “However, further investigations are warranted to better determine which patients may benefit from treatment beyond progression [TBP] to avoid excessive duration of therapy.”

According to the study, patients with cancer can benefit from treatment with targeted therapies after initial RECIST progression.

“Tumor flare in patients treated with immunotherapies may be due to transient immune cell infiltration into the tumor or to tumor growth that can occur while the immune system is priming for an antitumor response,” the researchers noted. “Tumor flare may result in patients discontinuing therapy before demonstration of a true clinical benefit.”

This subgroup analysis of CheckMate 025 included patients who were continuing to tolerate therapy with nivolumab and were exhibiting investigator-assessed clinical benefit. These patients were eligible for TBP and received nivolumab 3 mg/kg every 2 weeks for 4 weeks or longer after their first progression. They were compared with patients not TBP who received therapy from 0 to 4 weeks after progression.

Of the 406 patients, 78% progressed by RECIST criteria; 48% were TBP and 52% were not TBP. Of the patients TBP with nivolumab, 31 had achieved complete or partial response, 51 had stable disease, and 70 had progressive disease as their best response.

Prior to undergoing TBP, the objective response rate was 20% for patients TBP and 14% for patients not TBP. The researchers identified several clinical characteristics at first progression in patients TBP compared with not TBP, including better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life.

“These favorable disease characteristics may represent the benefit that influenced the investigator’s decision to treat the patient beyond progression and, independent of continued treatment, may impact survival,” the researchers wrote. “In an exploratory descriptive analysis that compared demographic and baseline disease characteristics of patients who responded to treatment beyond first progression vs those who did not, characteristics such as favorable Memorial Sloan Kettering Cancer Center risk score were identified in patients TBP who benefited, not surprising given that this is a feature of better prognosis.”

After progressing, 13% of patients TBP had a 30% or greater reduction in tumor. This group included patients with complete/partial response, stable disease, and progressive disease as their best response prior to TBP.

“This analysis from a large, international, phase III study is consistent with results from the phase II study, demonstrating that patients TBP with nivolumab resulted in additional clinical benefit as evidenced by 13% of patients experiencing a subsequent 30% decrease in tumor burden,” the researchers concluded.