Brazil Renal cell carcinoma (RCC) has undergone a profound therapeutic transformation over the past two decades. The management of metastatic clear-cell RCC has moved from cytokine-based approaches to vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), immune checkpoint inhibitors, and combinations of immunotherapy and targeted therapy.
Sunitinib, once the standard first-line treatment for metastatic RCC, established VEGFR inhibition as a central component of systemic therapy. The subsequent development of immune checkpoint inhibitors fundamentally changed the treatment landscape. In the phase III CheckMate 214 trial, nivolumab plus ipilimumab produced superior overall survival and objective response rates compared with sunitinib in patients with intermediate- or poor-risk disease. At a median follow-up of 25.2 months, 18-month overall survival was 75% with nivolumab plus ipilimumab versus 60% with sunitinib, with a hazard ratio for death of 0.63 (Motzer et al., 2018).
Other phase III trials subsequently established combinations such as pembrolizumab plus axitinib and nivolumab plus cabozantinib as effective first-line options for advanced RCC. These regimens progressively shifted the therapeutic objective from disease control with single-agent VEGFR inhibition toward deeper and more durable responses through complementary mechanisms of action.
The treatment paradigm has therefore changed substantially. Yet access to this progress has not changed at the same pace in Brazil.
What Does Metastatic Renal Cell Carcinoma Treatment Look Like in Brazil?
Brazil has a universal public healthcare system, the Sistema Único de Saúde (SUS), alongside
a large private and supplementary healthcare sector. In renal cell carcinoma, these two systems increasingly operate at different therapeutic speeds.
In 2019, the Brazilian Ministry of Health incorporated sunitinib and pazopanib into the SUS for patients with metastatic clear-cell RCC. At the time, this represented a genuine advance, providing access to two established VEGFR-targeted therapies for advanced disease. But the timing is worth pausing on: CheckMate 214 had already reported its practice-changing survival data a year earlier, in 2018. By the time sunitinib was incorporated into the SUS, however, international treatment standards had already begun to shift toward immune checkpoint inhibitor–based strategies. Nearly a decade later, sunitinib monotherapy remains, for a substantial share of SUS patients, the only systemic option available in the first-line metastatic setting, despite having been superseded as a preferred standard of care in international guidelines for more than seven years.
The evidence supporting first-line treatment of metastatic RCC has moved well beyond VEGFR-TKI monotherapy. Contemporary international guidelines increasingly prioritize immune checkpoint inhibitor–based combinations according to prognostic risk, disease characteristics, comorbidities, and patient preferences. This creates a widening gap between the treatment options supported by contemporary clinical trials and the therapies that are consistently accessible to patients treated within the public system.
The issue is not simply whether a medication exists in Brazil. Regulatory approval, reimbursement, incorporation into a healthcare system, institutional availability, procurement, and the capacity to administer and monitor treatment are distinct steps. A therapy approved by the Brazilian Health Regulatory Agency (ANVISA) is not automatically available to every patient treated through the SUS.
The private healthcare sector illustrates this difference. The Brazilian supplementary health system has incorporated modern RCC combinations into its coverage framework: current ANS (Agência Nacional de Saúde Suplementar) coverage documentation includes axitinib in combination with pembrolizumab as first-line therapy for advanced or metastatic RCC in patients with intermediate or poor-risk disease.
Thus, two patients with the same diagnosis, stage, and prognostic category can encounter fundamentally different treatment pathways depending on the healthcare system through which they receive care — a difference measured not in nuance, but in treatment generations.
While Metastatic Disease Remains Unequally Treated, Is Adjuvant Therapy Already the Next Discussion?
The contrast becomes even more striking when the focus shifts from metastatic to localized
disease.
For decades, adjuvant treatment after nephrectomy in RCC produced disappointing results. Several VEGFR-TKIs were evaluated, with inconsistent findings and no demonstrated overall survival benefit. This changed with the phase III KEYNOTE-564 trial.
In KEYNOTE-564, patients with clear-cell RCC at increased risk of recurrence after surgery were randomized to pembrolizumab or placebo for approximately one year. At the initial analysis, pembrolizumab significantly improved disease-free survival, with a 24-month disease-free survival rate of 77.3% versus 68.1% and a hazard ratio for recurrence or death of 0.68 (Choueiri et al., 2021).
The subsequent overall survival analysis strengthened the importance of these findings. After a median follow-up of 57.2 months, the hazard ratio for death was 0.62, and estimated overall survival at 48 months was 91.2% with pembrolizumab compared with 86.0% with placebo (Choueiri et al., 2024).
Adjuvant pembrolizumab therefore introduced an entirely new discussion in RCC: not simply how to treat measurable metastatic disease, but whether systemic immunotherapy should be administered to selected patients after complete surgical resection to reduce the risk of recurrence.
This discussion has continued to evolve in Brazil. On July 21, 2026, ANVISA approved a new adjuvant indication for pembrolizumab in combination with belzutifan for adults with clear-cell RCC at intermediate-high or high risk of recurrence after nephrectomy, with or without resection of metastatic lesions (ANVISA Resolução RE no 2.831/2026).
The pace of innovation is therefore unmistakable. But it raises an uncomfortable question: how do we discuss increasingly sophisticated adjuvant strategies in a country where access to contemporary systemic therapy for metastatic RCC remains profoundly heterogeneous — where some patients still start their treatment journey with a drug that was already a step behind the evidence at the moment it was incorporated?
Are We Dealing With Two Standards of Care?
The Brazilian RCC landscape increasingly reflects two different standards of care.
In the private sector, clinicians discuss which immune checkpoint inhibitor combination provides the best balance between efficacy, toxicity, quality of life, and long-term disease control. For patients undergoing nephrectomy, the discussion has expanded to include recurrence risk, adjuvant immunotherapy, and increasingly complex questions regarding treatment selection.
In the public sector, the fundamental question is often different: which systemic treatments are actually available to the patient?
This disparity is not unique to RCC. Oncology in Brazil has long faced differences in access to diagnostic technologies, molecular testing, radiation therapy, surgical expertise, and systemic treatments. RCC, however, provides a particularly clear example because its therapeutic landscape has evolved so rapidly — and because the distance between what is approved and what is delivered can now be measured not in months, but in treatment eras.
The problem is not simply that some patients receive an older drug while others receive a newer one. The problem is that the same diagnosis increasingly leads to different therapeutic possibilities depending on where the patient enters the healthcare system.
A patient with high-risk localized RCC in one setting is being evaluated for an adjuvant immune based strategy after complete surgical resection. Another patient with metastatic RCC in a different setting may still have limited access to the combination regimens that have defined contemporary first-line therapy since 2018.
Both patients are being treated in Brazil. Both have RCC. But they are not being treated according to the same therapeutic era.
The progress of RCC treatment should therefore be measured by more than the number of new drugs approved or positive phase III trials published. It also needs to be measured by how quickly those advances become accessible to the population that needs them.
For Brazilian oncology, the central challenge is no longer simply identifying what works. It is determining who gets access to what works.
References
Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in
Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14):1277-1290.
Choueiri TK, Tomczak P, Park SH, et al. Adjuvant Pembrolizumab after Nephrectomy in
Renal-Cell Carcinoma. N Engl J Med. 2021;385(8):683-694.
Choueiri TK, Tomczak P, Park SH, et al. Overall Survival with Adjuvant Pembrolizumab in
Renal-Cell Carcinoma. N Engl J Med. 2024;390(15):1359-1371.
Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant Pembrolizumab plus Belzutifan for
Renal-Cell Carcinoma. N Engl J Med. 2026;395(1):32-43.
Agência Nacional de Vigilância Sanitária (ANVISA). Resolução RE no 2.831/2026. Diário Oficial
da União, 21 jul. 2026.
