ASCO 2018: Phase III Trial Finds Many People with Advanced Kidney Cancer Do Not Need Surgery

Truckee, CA (UroToday.com) A randomized phase III clinical trial showed that many people with advanced kidney cancer can avoid surgery to remove the kidney (nephrectomy), without compromising survival.  The median overall survival for people who received only the targeted therapy sunitinib (Sutent®) was 18.4 months, compared to 13.9 months for those who received surgery followed by sunitinib, the current standard of care. 

These findings will be presented in ASCO’s Plenary Session, which features four studies deemed to have the greatest potential impact on patient care, out of the more than 5,800 abstracts featured as part of the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting. 

“Until now, nephrectomy has been considered the standard of care for patients with kidney cancer who have metastatic disease when the cancer is first diagnosed. These cases account for about 20% of all kidney cancers worldwide,” said lead study author Arnaud Mejean, MD, a urologist at the Department of Urology, Hôpital Européen Georges-Pompidou - Paris Descartes University in Paris, France. “Our study is the first to question the need for surgery in the era of targeted therapies and clearly shows that surgery for certain people with kidney cancer should no longer be the standard of care.” 
In addition to putting patients at risk for complications, including blood loss, infection, pulmonary embolism, and heart problems, nephrectomy delays medical treatment for people with advanced kidney cancer for weeks. In some cases, the cancer worsens so rapidly during this delay that there is no time to start systemic treatment. 

About the Study: The CARMENA trial enrolled 450 patients with synchronous metastatic renal cell carcinoma (mRCC), meaning that metastases were already present when kidney cancer was first diagnosed. An estimated 40,000 to 50,000 people each year are diagnosed with this type of cancer.1,2 

The patients were randomly assigned to receive surgery followed by sunitinib or sunitinib alone. In the surgery group, patients started sunitinib 4-6 weeks after surgery to allow time for recovery from surgery. 

Key Findings: Patients were followed for a median time of 50.9 months. Survival was not worse with sunitinib alone than with surgery and sunitinib. This was true for the study population as a whole (median survival was 18.4 months without surgery vs. 13.9 months with surgery), as well as for subgroups with an intermediate (median survival was 23.4 months vs. 19 months) and poor prognosis (median survival was 13.3 months vs. 10.2 months) groups. 

The difference in median survival seems to suggest a greater benefit with sunitinib alone. However, this cannot be concluded, as this trial was not designed to prove that one treatment is superior to the other, noted Dr. Mejean. 

The rate of tumor response to therapy (tumor shrinkage) was the same in the two treatment groups (27.4% and 29.1%) and the median time until the cancer worsened was slightly longer for patients who received sunitinib alone compared with those who also had surgery (8.3 months vs. 7.2 months). Clinical benefit was experienced by 47.9% of patients treated with sunitinib only, compared with 36.6% of patients treated by surgery and sunitinib. 

The authors remarked that kidney surgery is still the gold standard for people who do not need systemic therapy, such as those with only one metastasis. Those patients were not included in this clinical trial. 

Next Steps: Some patients in the study had a very good response to sunitinib alone and received surgery after completing systemic treatment. The researchers plan to continue following outcomes in these patients, as well as in other subgroups of study participants. Genomic research on tumor tissue collected on the study is underway. 

This study received funding from PHRC (French governmental grants for clinical research). 

Study at a Glance
Disease: Metastatic Kidney Cancer
Trial Phase, Type: Phase III, Randomized
Patients on Trial: 450
Intervention Tested: Surgery followed by sunitinib (standard of care) vs. sunitinib alone
Primary Finding: mOS 13.9 months with standard of care vs. 18.4 months with sunitinib alone
Secondary Finding(s): mPFS 8.3 months with standard of care vs. 7.2 months with sunitinib alone

References: 
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr. Accessed July 16, 2013.
2. The epidemiology of renal cell carcinoma. Ljungberg B1, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA. Eur Urol. 2011 Oct;60(4):615-21.

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