A phase 3 trial of sunitinib alone versus nephrectomy followed by sunitinib in patients with intermediate- and poor-risk metastatic renal cell carcinoma (RCC) suggests surgery may not always be necessary.
The CARMENA trial presented at the ASCO 2018 meeting and published in NEJM found overall survival was better in patients treated with the targeted therapy alone (18.4 v 13.9 months).
“For the past 20 years, the standard of care for these patients has been surgery and systemic therapy,” said Dr Arnaud Méjean, of Hôpital Européen Georges-Pompidou at Paris Descartes University.
“Since 2005, the standard has been cytoreductive nephrectomy plus sunitinib. However, the role of nephrectomy in this era of targeted therapy is in question.”
#CARMENA french trial is released today! GAME CHANGER Breaking News no more CYTOREDUCTIVE NEPHRECTOMY in metastatic #kidneycancer ! 450 pts: Sunitib alone was not inferior to nephrectomy + sunitinib for OS! Stop surgery in these patients #eauguidelines #ASCO18 @ASCO @AFUrologie pic.twitter.com/Yg6dobpnOJ
— Morgan Roupret (@MRoupret) June 3, 2018
The CARMENA trial was a prospective, randomised trial including 450 patients with metastatic clear cell RCC and a median follow-up of 50.9 months.
Slightly more than half of each group had an intermediate MSKCC risk score, and the remainder had an MSKCC poor risk score. Patients in both groups had a median of two metastatic sites. The most common metastatic sites included the lung, bone and lymph nodes.
The European study found in an intention-to-treat (ITT) analysis that sunitinib alone was noninferior to nephrectomy plus sunitinib overall in both MSKCC subgroups.
“When medical treatment is required, cytoreductive nephrectomy should no longer be considered the standard of care in metastatic RCC,” Dr Méjean said
Speaking at an ASCO press conference Dr Sumanta Pal, of the City of Hope Comprehensive Cancer Center in the US, supported the findings.
“It has really sort of flipped the existing paradigm that we have in the management of advanced kidney cancer in this regard.”
Given the rapidly evolving landscape in the management of kidney cancer, including new trials and drug approvals just in the past few months, “we may have to go back to the drawing board once again and assess the relevance of removing the primary tumor,” he said.
Will #CARMENA trial change your clinical practice? #ASCO18 #RCC @DrChoueiri @montypal @DrDanielHeng @FabioSchutz78 @AlbigesL @MichaelStaehler @sogug1 @docjavip
— Guillermo de Velasco (@g_develasco) June 4, 2018
However an editorial in the NEJM said nephrectomy in properly chosen patients with metastatic renal-cell carcinoma remained an essential component of care.
Citing trial issues with patient selection and intention-to-treat, the authors said clinicians should not yet abandon surgery.
“The main focus is on pretreatment risk features, resectability of the primary tumor, status of health, and presence of other medical conditions in determining who is most likely to benefit.”