Renal cell

 Adjuvant

1. Review path report

2. Assess comorbidities including contraindications for IO

3. Assess individual risk of recurrence UCLA risk calculator   FOX CHASE calculator

Keynote 564 trial:  Pembro offered OS and DFS benefits compared to placebo.

 The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group.

2nd line after 1st line TKI+IO: cabozantinib ( METEOR, CONTACT-03, CANTATA trials) , everolimus+ lenvatinib ( this can be used 3rd if pt gets cabozantinib second line)

3rd line: Belzutifan ( LITESPARK trial versus everolimus)

The LITESPARK-005 trial is a pivotal clinical study that evaluated the efficacy and safety of belzutifan in patients with advanced renal cell carcinoma (RCC) who had progressed following treatment with both a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor. This open-label, randomized, head-to-head trial included 746 patients who were randomized to receive either belzutifan or everolimus. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

The trial demonstrated a statistically significant improvement in PFS for belzutifan compared to everolimus, with a hazard ratio (HR) of 0.75 (95% CI, 0.63-0.90; one-sided p-value = 0.0008). The median PFS was 5.6 months in both treatment arms, but the Kaplan-Meier curves indicated nonproportional hazards. The confirmed objective response rate was 22% for belzutifan and 3.6% for everolimus. Although the OS results were not fully mature, there was a favorable trend for belzutifan (HR, 0.88; 95% CI, 0.73-1.07).

Belzutifan was generally well-tolerated, with fewer drug discontinuations and interruptions due to treatment-emergent adverse events compared to everolimus. This trial led to the FDA's approval of belzutifan for patients with advanced RCC following prior treatment with a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor.

Oligometastatic RCC

The study by Tang et al. published in The Lancet Oncology in 2021 evaluated the feasibility and efficacy of SBRT in deferring systemic therapy for patients with oligometastatic RCC. This single-arm, phase 2 trial included patients with five or fewer metastatic lesions who were treated with SBRT to all lesions. The study found that SBRT could effectively defer systemic therapy, with a median progression-free survival (PFS) of 22.7 months and a 1-year PFS rate of 64%.

Additionally, the study by Liu et al. in the World Journal of Urology in 2021 demonstrated that complete eradication of tumor burden with SBRT was associated with improved progression-free survival and cancer-specific survival in patients with oligometastatic RCC. The 1-year local control rate was 97.3%, and patients who received complete SBRT had significantly longer PFS and CSS compared to those who received no or incomplete SBRT

FH mutated papillary RCC stage 4- Erlotinib+ avastin

The KEYNOTE-B61 trial showed that it worked as a first-line treatment option for advanced non-clear cell renal cell carcinoma. There’s some evidence from a phase 2 single-arm trial on everolimus/lenvatinib, but not as much evidence as for other treatment options.