1. Fuerst, Mark L.

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CHICAGO-Many advanced kidney cancer patients who receive sunitinib can avoid surgical removal of the kidney without compromising survival, according to a new study.


Approximately 20 percent of patients with kidney cancer present with metastatic renal cell carcinoma at first diagnosis. "For the past 20 years, the standard of care for these patients has been surgery (cytoreductive nephrectomy) and systemic therapy. In the past 10 years, many targeted therapies, such as sunitinib, have shown survival benefits in trials and are approved for treating these patients," said lead author Arnaud Mejean, MD, a urologist at the Department of Urology, Hopital Europeen Georges-Pompidou-Paris Descartes University in Paris, France.


He presented the results of the study at a press conference at the 2018 ASCO Annual Meeting (Abstract LBA3). They were published simultaneously in the New England Journal of Medicine (2018; doi:10.1056/NEJMoa1803675).


"Compared directly with targeted therapy, does upfront nephrectomy still offer a survival benefit?" asked Mejean. "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.


The prospective, randomized, phase III non-inferiority Cancer Renal MEtastatique Nephrectomie Antiangiogenique (Carmena) trial enrolled 450 patients from 79 centers with synchronous metastatic renal cell carcinoma. An estimated 40,000 to 50,000 patients each year are diagnosed with this type of cancer.


The patients were randomly assigned to receive nephrectomy followed by sunitinib (226 patients) or sunitinib alone (224 patients). In the surgery group, patients started sunitinib 4-6 weeks after surgery to allow time for recovery from the procedure.


Key Findings

After a median follow-up of 50.9 months, median overall survival (OS) was higher in the nephrectomy plus sunitnib arm (18.4 months) than in the sunitinib alone arm (13.9 months). "The non-inferiority condition was met," said Mejean. The hazard ratio for Arm A versus Arm B was 0.89.


This finding held up for subgroups with an intermediate (median OS 23.4 months vs. 19 months, respectively) and poor prognosis (median OS 13.3 months vs. 10.2 months, respectively).


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 Mejean.


The rate of tumor shrinkage was similar in the two treatment groups (27.4% and 29.1%) and the median time until progress 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 percent of patients treated with sunitinib alone as compared with 36.6 percent of patients treated by surgery and sunitinib.


Kidney surgery is still the gold standard for people who do not need systemic therapy, such as those with only one metastasis, he said. Those patients were not included in this clinical trial.


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, he said.


In conclusion, Mejean noted, "Sunitinib alone is not inferior to nephrectomy followed by sunitinib. Non-inferiority for OS was demonstrated in patients with both intermediate-risk and with poor-risk prognostic factors. Progression-free survival and clinical benefit were greater with sunitinib alone compared with nephrectomy followed by sunitinib.


"When medical treatment is required, cytoreductive nephrectomy should no longer be considered the standard of care in metastatic renal cell carcinoma."


ASCO Expert Sumanta K. Pal, MD, Associate Clinical Professor, Department of Medical Oncology & Therapeutics Research at City of Hope in Duarte, Calif., commented: "Thanks to this research, many patients with advanced kidney cancer can be spared unnecessary surgery and a host of severe side effects that often accompany it. These findings will likely lead to a dramatic change in treatment for people who are diagnosed with metastatic kidney cancer.


"We need to take the results with a grain of salt," he added. "Treatment for advanced kidney cancer has evolved with the approval of combination immunotherapy with nivolumab plus ipilimumab. We may have to go back and assess the relevance of removing the primary tumor."


Mark L. Fuerst is a contributing writer.