Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma
A newer report of this study has been published: Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy? (2021)
- Study type
- Clinical trial
- Study name
- CARMENA
- Phase
- Phase 3
- Design
- Randomised non-inferiority trial (1:1 ratio)
- Sample size
- 450 patients
- Source
- N Engl J Med · 2018
- Trial registration
- NCT00930033
In plain words
In the past, when kidney cancer had already spread at diagnosis, the affected kidney was usually removed first and then medicine was started. In this study, patients at intermediate or high risk who received only the medicine (sunitinib) did not live shorter lives than those who had surgery first. So in many of these patients, drug treatment can be started without immediate surgery, although surgery still has a place in some carefully selected patients.
Key results
Treatment arms and regimens
Cytoreductive nephrectomy, then sunitinib 50 mg daily in cycles of 28 days on and 14 days off (every 6 weeks).
Sunitinib 50 mg daily in cycles of 28 days on and 14 days off (every 6 weeks), without nephrectomy.
Source of the regimen details: Published abstract (NEJM 2018)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with confirmed metastatic clear-cell renal-cell carcinoma at diagnosis who were suitable candidates for nephrectomy and had intermediate or poor prognostic risk by the MSKCC model; ECOG performance status 0 to 1 and no prior systemic therapy (ClinicalTrials.gov).
Endpoints
Primary endpoint: overall survival (non-inferiority design; upper limit of the 95% CI of the hazard ratio ≤1.20).
Safety and side effects
Adverse events in each group were as expected (details in the full paper).
Clinical significance and place in guidelines
CARMENA called into question the routine use of immediate cytoreductive nephrectomy in intermediate- and poor-risk patients. The EAU 2022 guideline recommends against cytoreductive nephrectomy in MSKCC poor-risk patients (strong recommendation) and, in intermediate-risk patients with an asymptomatic primary tumour who need systemic therapy, starting systemic therapy without immediate nephrectomy (weak recommendation). NCCN (version 3.2022) recommends cytoreductive nephrectomy in selected patients with a potentially resectable primary tumour and stresses the importance of patient selection.
Limitations
Conducted in the era of targeted therapy (sunitinib) before combination immunotherapy; slow accrual and early termination; a large proportion of patients were poor-risk, which limits generalisation to lower-risk patients.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.