Clear cell renal cell carcinoma (ccRCC) is an archetype for the successful application of immunotherapy, but little is known about the utility of immune checkpoint inhibitors for the treatment of brain metastases in this disease. CheckMate 025 established nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, as a standard of care in ccRCC after progression through anti-angiogenic therapy.
Patients with evidence of intracranial metastases were excluded from this and all subsequent trials of immune checkpoint inhibitors in ccRCC, typically because of the recognition of brain metastases as a marker of poor prognosis and a potential complicating factor in assessing toxicity of a novel agent. Outside anecdotal reports, little to no formal effort has been made to measure the activity of anticancer agents in the setting of brain metastases in ccRCC. Given that 10% of patients with metastatic ccRCC will develop intracranial metastases, addressing the role that immune checkpoint inhibitors play in the management of brain metastases remains an important need in the field of oncology.
In the article that accompanies this editorial, Flippot et al report results from GETUG-AFU-26-NIVOREN, a multicenter, phase II trial of nivolumab in patients with metastatic ccRCC who had progressed during or after at least one prior line of anti-angiogenic treatment. In this study, patients with brain metastases were not excluded. In a prospectively identified cohort of patients with asymptomatic brain metastases who had not undergone local therapy, nivolumab showed disappointing activity: objective responses were seen in only four (12%) of 34 evaluable patients. Furthermore, 17 (50%) of 34 patients progressed through therapy. These results compare unfavorably with an extracranial response rate of 21% in the same cohort. In contrast, the objective response rates in a preliminary analysis of the total NIVOREN population was 19%, whereas the objective response rate in CheckMate 025 was 25%.
The authors compared the NIVOREN cohort with another prospectively identified cohort of patients with brain metastases who had undergone prior local therapy. Here, they found that the untreated cohort had a higher risk of intracranial progression (hazard ratio, 0.49; 95% CI, 0.26 to 0.92) after adjustment for baseline characteristics. Overall survival was equal between the two groups.
Fonte: Journal of Clinical Oncology