Immune checkpoint blockade in renal cell carcinoma

Abstract

Immune checkpoint blockade (ICB) is the foundation of current first‐line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long‐lasting remissions. With the expanding arsenal of ICB‐based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.

Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma

“…Checkpoint interactions, such as PD-1:PD-L1, CTLA4:B7-1/2, T-cell immunoglobulin and mucin domain-3 (TIM-3):Galectin-9, and lymphocyte activation gene-3 (LAG-3):MHC class II, play an important role in immune evasion of cancers [1]. Drug Administration (FDA) for mRCC include those that block co-inhibitory molecules, such as cytotoxic T-lymphocyte activating protein-4 (CTLA-4), PD-1, and PD-L1, thus facilitating T cell effector function and anti-tumor response [52,53].…”

“…As ICIs are superior to conventional TKIs [122], ICI-based therapies are now the standard of care for patients with mRCC [52,53]. A substantial subset of mRCC patients do not respond to ICIs, and patients who initially respond, eventually progress [62,123].…”

“…The dominant challenge is to identify an optimal combination of these two treatments and obtain the optimal dosage of combined therapy to magnify the clinical benefits [124]. The therapeutic potential of combinatorial approaches targeting checkpoint molecules alone or in combination with other checkpoint blockers, targeted therapies, or radiation have been extensively explored [16,52,53,[125][126][127]. Although trials to date have largely included patients with previously untreated BM, the use of multiple treatments and their efficacy remains largely unexplored.…”

“…Improved anti-tumor immunity in the brain may also be mediated by combinations of antiangiogenic agents and ICIs [150,151]. Recently, the FDA approved two ICIs plus TKI combinations for mRCC: pembrolizumab plus axitinib and avelumab plus axitinib as firstline treatment in untreated intermediate and poor-risk subsets [1,16,53,126,133,150,152]. Both combinations were tested against the TKI sunitinib in large, randomized, multi-center trials and demonstrated improved median PFS with a 4-5-to month margin and superior overall ORR [1,122,126,152].…”

“…Both combinations were tested against the TKI sunitinib in large, randomized, multi-center trials and demonstrated improved median PFS with a 4-5-to month margin and superior overall ORR [1,122,126,152]. Promising data from trials confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus lenvatinib as first-line treatment for mRCC [53,153].…”