Second-line treatment in renal cell carcinoma: clinical experience and decision making

Abstract

Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients’ outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints. These two approaches, practically represented by the use of either cabozantinib or nivolumab, seem to remain a rational therapeutic approach also when first-line immune-based combinations are used. The objective of this study is to design a preferential therapeutic pathway for the second-line treatment of mRCC. The procedure applied in this project was a group discussion, based on the Nominal Group Technique (NGT) method in a meeting session, aimed at defining the therapeutic choice for the second-line treatment of mRCC. The NGT process defined the most relevant parameters that, according to the interviewed panelists, clinicians should consider for the selection of the second-line therapy in the context of advanced renal cell carcinoma of mRCC. The algorithm developed for the treatment selection as a result of this process should thus be considered by clinicians as reference for therapy selection. Plain language summary The result of this paper was the definition of an algorithm intended to suggest a preferential therapeutic pathway considering both the outputs of the Nominal Group Technique (NGT) process and the actual clinical practice and the experience of selected panelists. During the NGT process and the discussion phase, panelists defined the most important parameters to be included in the algorithm that are important for the treatment definition. Cabozantinib and nivolumab are identified as the most reasonable therapeutic options for patients progressing after first-line treatment and are the medication options included in the algorithm for therapy selection.

The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis

“…In the era of tyrosine kinease inhibitors (TKIs), ICIs and their combinations for mRCC, baseline clinical, and laboratory characteristics of patients incorporated into the IMDC score (37,38) still represent the critical factors clinicians consider for the treatment decision making (2,3,39). More recently, we proposed implementing the IMDC prognostic stratification by the Meet-URO score, which was demonstrated in large series (34,40) to be more accurate than IMDC alone by two additional independent prognostic factors (the presence of bone metastases and the NLR).…”

Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma

“…Additionally, the variation in OS curves crossing may also be reflective of differences in subsequent treatment in the different ICI + TKI and SUN arms. Highly effective subsequent treatment (e.g., ICI, ICI + TKI or ICI + ICI treatment) can be given after progression on SUN [ 41 ], which biases and increases OS in the SUN arm of some trials. Use of subsequent ICI treatment might have been twice as high in CLEAR and KEYNOTE-426 SUN arms compared with JAVELIN renal 101 and CheckMate 9ER SUN arms [ 27–30 ].…”

Sodium Levels and Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Nivolumab

“… 6 Identifying the most suitable sequence of postprogression treatments presents a clinical difficulty, because it greatly depends on such variables as prior treatment, the extent of disease, tumor characteristics, and the patient’s medical background and current health condition. 7 The selection of the most suitable therapy for mRCC is primarily based on clinical features and biochemical examination. However, there is a pressing need to explore potential new prognostic markers.…”