Cure in Advanced Renal Cell Cancer: Is It an Achievable Goal?

Abstract

Immunotherapy has historically been of interest in the management of metastatic renal cell cancer (mRCC) because of its relative chemoresistance and the reproducible but low incidence of spontaneous remission in metastatic disease. Recently, targeted immunotherapies in the form of checkpoint inhibitors have shown durable responses in approximately 20%-30% of patients with solid tumors, with a much more acceptable side-effect profile. Anti-programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 antibodies rely on the presence of host T cells in the tumor microenvironment to be stimulated in order to activate an antitumor response. The presence of tumor antigens augments this stimulation. This has led to further research into combination therapy with anti-PD-1 inhibitors and radiotherapy, chemotherapy, or targeted therapy with the aim of increasing the response rate to these agents. We describe three cases of patients with mRCC treated with anti-PD-1 antibody therapy in combination with targeted therapy (bevacizumab), anti-cytotoxic T lymphocyte antigen 4 therapy (ipilimumab), or radiotherapy. We perform a comprehensive literature review on combination immunotherapy and the scope for the future. Two patients had a complete clinical response within 3 months of commencing treatment. The third patient had a further significant response to radiotherapy outside the field of treatment after initial response to anti-PD-1 therapy, which lasted for over 12 months. We are now in the era of immunotherapy with promising results in select patients. However, the number of complete remissions with single agents are low. This report demonstrates the potential for combination therapy in mRCC to produce complete responses and improved survival rates. Whether these results equate to cure in a subset of patients requires longer follow-up. Further evaluation of dosing regimens, sequencing methods, and biomarkers to select patient population is required to advance this treatment strategy. Multiple phase I-III studies exploring the benefit of combination immunotherapy are currently under way. Further research into predictive biomarkers to identify the cohort of patients who gain this benefit is pertinent. This case series demonstrates that the combination of immunotherapy with other treatments can lead to complete responses, even in patients with initially bulky disease. Combination therapy with immunotherapy seems to cause more durable responses in patients with metastatic renal cell cancer compared with monotherapy. Significantly longer follow-up is necessary to determine whether durable complete response confers a cure in a select group of patients.