Update on the most promising biomarkers of response to immune checkpoint inhibitors in clear cell renal cell carcinoma.

In the last few years, the standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically with the emergence of the immune checkpoint inhibitors (ICI): anti-PD(L)-1 used as a monotherapy or as in combination either with an anti CTLA-4 or with an anti-angiogenic molecule (VEGFR tyrosine kinase inhibitor (TKI)). These combinations are now recommended in first line setting for mccRCC, according to the last European recommendations. In the face of these new therapeutic options, the question of selecting the best treatment arises as well as the optimal sequence. Predictive biomarkers are required to guide the therapeutic choice and provide a personalized treatment for each patient. This narrative review will provide an overview of the main predictive biomarkers assessed in mccRCC treatment, with a particular focus on mRNA panel signatures.

Association of Energy Expenditure and Efficacy in Metastatic Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: Nivolumab improved patients' survival in metastatic renal cell carcinoma (mRCC). We aimed to evaluate resting energy expenditure (REE) (i.e., patients' basal metabolism) to predict efficacy. Methods: We conducted a monocentric, observational study of mRCC patients receiving nivolumab between October 2015 and May 2020. REE was measured prior to initiating immunotherapy using indirect calorimetry to determine hypo, normo and hypermetabolism. Primary endpoint was 6-month, progression-free survival (PFS), and secondary endpoints were response rate, PFS and overall survival (OS). Results: Of the 51 consecutive patients, 15 (29%) were hypermetabolic, 24 (47%) normometabolic, and 12 (24%) hypometabolic. The 6-month PFS was 15% for hypermetabolic patients and 65% for non-hypermetabolic patients (p < 0.01). In the multivariate analysis, hypermetabolism was the only baseline factor predicting 6-month PFS (OR 9.91, 95%CI [1.62−60.55], p = 0.01). Disease progression was noted as the best response in 73% of hypermetabolic patients and 26% of non-hypermetabolic patients (p = 0.02). Median PFS was 2.8 and 8.7 months (p < 0.01), and median OS was 20.2 and 35.1 months (p = 0.13) in the hypermetabolic and non-hypermetabolic groups, respectively. Conclusions: Our study identifies an association between mRCC patients' energy expenditure and nivolumab efficacy. The measurement of REE by indirect calorimetry in routine practice could help identify patients at risk of nivolumab failure.

Cabazitaxel multiple rechallenges in metastatic castration-resistant prostate cancer.

INTRODUCTION: Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges. PATIENTS AND METHODS: We retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor-targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression-free survival, prostate-specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points. RESULTS: Twenty-two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression-free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life-extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia. CONCLUSION: Cabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it. NOVELTY & IMPACT STATEMENTS: Patients with metastatic castration-resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor-targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity.