Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Abstract

Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future.

Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation

“…5,8 Liver toxicity has also been reported in studies with other antiÀPD-(L)1 agents as monotherapy and in combination with EGFR TKIs. 7,9,10 The ORR observed with pembrolizumab plus erlotinib was similar to that reported in previous first-line March 2019 Pembrolizumab + Erlotinib/Gefitinib for NSCLC monotherapy studies. 6,11,12 Although the ORR in patients with PD-L1 TPS greater than or equal to 50% (4 of 4; 100%) is noteworthy, as was the durability of response in this group, there were too few patients to draw meaningful conclusions regarding possible additive or synergistic antitumor effects compared with monotherapy.…”

Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?

“…Recently, a better understanding of the biological and molecular basis of RCC has led to the development and approval of new targeted agents: the majority of these drugs are directed against the vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFRs) pathway (bevacizumab, sorafenib, sunitinib, pazopanib, axitinib and cabozantinib) [5][6][7][8][9]; the mammalian target of the rapamycin (mTOR) pathway (everolimus and temsirolimus) [10,11] and the PD-1/PD-L1 pathway (nivolumab) [12,13].…”

Debilitating Skin Toxicity Associated with Pembrolizumab Therapy in an 81-Year-Old Female with Malignant Melanoma

“…This new group of immune therapy includes CTLA-4 inhibitors (ipilimumab) to PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab), as well as numerous other molecules in the development. The clinical utility of these agents include melanoma [1] and renal cell carcinoma [2] as well as numerous malignancies not previously established as responsive to immunologically derived therapy.…”