Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.

Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy.

Many patients diagnosed with cancer adopt dietary changes and supplement use, and a growing body of evidence suggests that such modifications can affect outcomes to cancer therapy. We sought to assess the prevalence of these practices and the surrounding physician-patient dialogue among patients with metastatic renal cell carcinoma. An online survey was administered by Kidney Cancer Research Alliance (KCCure), interrogating dietary modification patterns, supplement usage, out-of-pocket expenditure related to supplements, and patients' views toward alternative medicine practices. Patients with metastatic renal cell carcinoma receiving combination therapy were actively solicited. In total, 289 unique responses were collected. The most common first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). Within the cohort, 147 (50.9%) started using supplements following diagnosis of renal cell carcinoma; the most utilized supplements were probiotics, cannabidiol (CBD) oil/marijuana, and Vitamin C, reported by 70 (47.6%), 61 (41.4%), and 54 (36.7%), respectively. Dietary modifications following cancer diagnosis were reported by 101 (34.9%) respondents, of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. Most respondents (71.3%) noted that they consistently report supplement usage to their physicians. A substantial proportion of patients with metastatic renal cell carcinoma utilize dietary modification and supplements as an adjunct to antineoplastic therapy. Considering the widespread adoption of these practices and the reported effects on cancer treatment, it is crucial for healthcare providers to engage in discussions with patients regarding supplement use.

Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer and Response to Checkpoint Inhibition.

This single-center cohort study assesses the association of tumor mutational burden status in patients with metastatic castration-resistant prostate cancer and response to immune checkpoint inhibitor therapy.