ASCO 2018: Sunitinib Alone Sufficient For RCC Patients With Limited Metastatic Burden

CARMENA findings allow more metastatic renal cell carcinoma patients to avoid cytoreductive nephrectomy

medwireNews: Sunitinib alone offers overall survival (OS) that is noninferior to that of nephrectomy followed by sunitinib therapy for patients with a limited metastatic renal cell carcinoma (mRCC) burden and a good performance status, research indicates.

The phase III CARMENA findings were reported at the ASCO Annual Meeting 2018 held in Chicago, Illinois, USA, and simultaneously reported in The New England Journal of Medicine.

Cytoreductive nephrectomy before targeted therapy has been shown to be useful for patients with a low metastatic tumour burden and an ECOG performance score (PS) of 0, but not beneficial for those with a high volume of metastases and a PS of 2 or above, reported Arnaud Méjean, from Hôpital Européen Georges-Pompidou - Paris Descartes University in France.

To determine the impact of nephrectomy among patients with a limited metastatic burden, an MSKCC intermediate or poor score, and a PS of 0–1, 450 patients who had operable mRCC and were eligible for sunitinib therapy were randomly assigned to undergo nephrectomy followed by sunitinib 50 mg/day on a 4 week on, 2 week off schedule (n=226) or to receive sunitinib alone (n=224).

At the interim intention-to-treat (ITT) analysis after a median of 50.9 months, the primary endpoint of median OS was 18.4 months with sunitinib alone versus 13.9 months with nephrectomy plus sunitinib, giving a hazard ratio (HR) of 0.89. The upper 95% confidence interval was 1.10 and met the noninferiority criteria of less than 1.20, the presenter reported.

This finding was true for both patients with an MSKCC intermediate and poor score. Consistent with these ITT findings, per protocol analyses also produced numerically longer OS with sunitinib alone and met noninferiority criteria.

ITT analysis showed a median progression-free survival of 8.3 months for the sunitinib only patients versus 7.2 months for the nephrectomy plus sunitinib arm, with a HR of 0.82, and again this was true for both the MSKCC intermediate and poor score subgroups, and replicated in the per protocol analyses.

The objective response rate was similar in the two trial arms, whereas the clinical benefit rate – defined as the proportion of patients who achieved disease control beyond 12 weeks – was significantly higher with sunitinib alone (47.9 vs 36.6%).

Arnaud Méjean told delegates that 38 (17.0%) of patients in the sunitinib arm subsequently underwent secondary nephrectomy a median of 11.1 months after randomisation to the study, for emergency treatment of the tumour (18.9%) or because the patient achieved a complete or near complete response to sunitinib at their metastatic sites (81.1%).

“Cytoreductive nephrectomy should no longer be considered the standard of care in metastatic renal cell carcinoma, at least when medical treatment is required”, he concluded.



Méjean A, Escudier B, Thezenas S, et al. CARMENA: Cytoreductive nephrectomy followed by sunitinib versus sunitinib alone in metastatic renal cell carcinoma – Results of a phase III noninferiority trial . J Clin Oncol 36, 2018 (suppl; abstr LBA3). 

Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma . N Engl J Med; Advance online publication 3 June 2018.
DOI: 10.1056/NEJMoa1803675

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