Recurrence/Progression Rates in Stage 4 Renal Cell Carcinoma
The majority of patients with stage 4 renal cell carcinoma will experience disease progression despite first-line therapy, with approximately 69-78% of patients progressing on immunotherapy and median progression-free survival ranging from 8-16 months depending on treatment regimen and risk stratification. 1, 2
Progression Rates by Treatment Regimen
Immunotherapy-Based Combinations
Nivolumab plus cabozantinib: Median PFS of 16.6 months, meaning approximately 50% of patients progress by this timepoint 2
Nivolumab plus ipilimumab: In intermediate/poor-risk patients, median PFS was 11.6 months, with 69% of patients experiencing progression during the trial period 1, 3
Pembrolizumab plus axitinib: Median PFS of 15.1 months in the intent-to-treat population 1
Nivolumab monotherapy: 78% of patients progressed after initial treatment, with 69% experiencing progression in phase 2 trials 1
Tyrosine Kinase Inhibitor Monotherapy
Sunitinib: Median PFS varies significantly by IMDC risk group 4:
Pazopanib: Median PFS of 11.1 months in treatment-naïve patients, with 9.2 months in the overall study population 1
Risk-Stratified Progression Patterns
IMDC risk stratification is critical for predicting progression rates, as outcomes vary dramatically 5, 4:
Favorable risk (0 factors): Median PFS exceeds 13-14 months with TKI monotherapy, with even better outcomes on combination immunotherapy 1, 4
Intermediate risk (1-2 factors): Median PFS of 10-11 months with TKI monotherapy, improved to 11-16 months with combination immunotherapy 1, 2, 4, 3
Poor risk (3-6 factors): Median PFS of only 2.4 months with sunitinib monotherapy, highlighting the aggressive nature of disease in this subgroup 4
Treatment Beyond Progression
A subset of patients may benefit from continuing immunotherapy beyond radiographic progression, though this represents a highly selected population 1:
Of patients treated with nivolumab beyond first progression, 69% experienced subsequent tumor reduction or stabilization 1
In CheckMate 025,48% of patients who progressed continued nivolumab for ≥4 weeks after progression, with 13% experiencing ≥30% tumor burden reduction 1
This strategy should only be considered in patients with clinical benefit, asymptomatic progression, and good performance status 1
Overall Survival Context
While progression is common, modern therapies have substantially improved overall survival 5, 2, 3:
- Median OS with nivolumab plus cabozantinib: 49.5 months 2
- Median OS with nivolumab plus ipilimumab (intermediate/poor risk): Not reached at 18 months, with 75% alive at 18 months 3
- Median OS with sunitinib: 26-35.5 months depending on trial 2, 3
Critical Caveats
Metastatic site significantly impacts progression risk, with bone and liver metastases conferring worse prognosis than lung-only disease 5
Performance status is paramount: Patients with Karnofsky performance status <80% have substantially higher progression rates across all treatment regimens 5
Complete response rates remain low (5-13% with combination immunotherapy), meaning most responding patients will eventually progress 1, 2, 3