Combination Therapy in Renal Cell Carcinoma: the Best Choice for Every Patient?

Abstract

Purpose of Review Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC. Recent Findings The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Summary Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.

Clinically approved combination immunotherapy: Current status, limitations, and future perspective

“…Like all treatments, combination immunotherapies have limitations and face important challenges. For example, it is unknown how different RCC patients will respond to the different first-line treatments of ICIs plus antiangiogenic agents and whether these combinations are the best option for all RCC patients ( Rossi et al, 2021 ). Similarly, personalized treatment approaches with robust predictive biomarkers are urgently needed to identify NSCLC patients responsive to the atezolizumab/bevacizumab/carboplatin/paclitaxel combination immunotherapy ( Wang et al, 2021 ).…”

Sunitinib-Induced Elevation of Mean Corpuscular Volume (MCV)—Exploring Its Possible Clinical Relevance in Cancer Patients

“…A recent meta-analysis on therapeutic alternatives to first-line sunitinib monotherapy in mRCC patients demonstrated the benefit of using combined immune therapy with checkpoint inhibitors [ 6 ]. A careful approach should be taken in patients with dysregulated immune activation such as pre-existing autoimmune diseases or hematopoietic/solid organ transplant or compromised immune function (long-term immunosuppression, chronic viral infections), and/or significant medical co-morbidities (organ dysfunction, elderly or frail patients, metastatic brain disease) [ 7 ]. However, these patients and possibly those with favorable risk may still benefit from sunitinib monotherapy [ 8 ].…”

“…However, these patients and possibly those with favorable risk may still benefit from sunitinib monotherapy [ 8 ]. Furthermore, the benefit of a selective sequential treatment strategy has been proposed [ 7 ].…”

Economic evaluation of first-line nivolumab plus cabozantinib for advanced renal cell carcinoma in China

“…Anti-angiogenic therapy with sunitinib, a small molecule tyrosine kinase inhibitor, has historically been an effective tool for the first-line treatment of patients with RCC characterized by the inactivation or deletion of the von Hippel-Lindau (VHL) gene ( 7 , 8 ). Sunitinib has been approved by the Food and Drug Administration as a first-line treatment for advanced and/or metastatic RCC (mRCC).…”