Patients with renal cell carcinoma may continue to benefit from treatment with nivolumab even after the disease has progressed, according a study published JAMA Oncology.
Still a relatively new line of treatments, immunotherapies such as nivolumab are diverse and not well understood. This is especially true in patients with RCC who, despite initial success while on with immunotherapies, eventually become resistant to treatment, leading to disease progression and low rates of 5-year survival.
Nivolumab, which works by blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2 to stimulate the body’s immune system to attack cancerous cells, demonstrated an ability to improve survival (25 months vs 19.6 months) with fewer grade 3 or 4 adverse events (19% vs 37$%) compared with the chemotherapy drug everolimus in the CheckMate 025 trial. However, using conventional criteria to evaluate disease response to immunotherapeutic treatment may lead to the discontinuation of treatment before the full clinical benefit has been realized.
To investigate this possibility, researchers led by Saby George, MD, Roswell Park Cancer Institute (Buffalo, NY), looked at 36 patients included in the trial who continued to receive nivolumab treatment more than 6 weeks after first progression, defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for measuring tumor response.
In these patients, objective overall response rate was 14% (5 patients) and median progression-free survival was 4.2 months prior to first progression, compared with 16% (15 patients) and 2.6 months, respectively, in patients who were not treated beyond progression.
Following initial progression, 25 patients (69%) who continued treatment experienced subsequent tumor reductions or stabilization in target lesion size. These patients also experienced more treatment-related adverse events than those who did not continue treatment (81% vs 66%); however, after adjusting for length of treatment exposure, the incidence of these events was actually lower in those that received nivolumab after initial disease progression (322.9 per 100 patient-years vs 518.7 per 100 patient-years).
From these results, researchers concluded that nivolumab may still have clinical benefit, as well as a manageable toxic profile, in patients with metastatic RCC after disease progression. Additional research is warranted to determine whether these results can be duplicated in larger-scale trials and to ensure the optimal use of immunotherapies in RCC.
