CHICAGO – While cytoreductive nephrectomy is generally still inadvisable in metastatic renal cell carcinoma patients who require medical therapy, an update of the CARMENA trial suggests the procedure may provide benefit for certain patients.
Patients with only one International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor may benefit from cytoreductive nephrectomy, said CARMENA investigator, in a presentation at the annual meeting of the American Society of Clinical Oncology.
Among patients in CARMENA treated with nephrectomy plus sunitinib, median overall survival was 31.4 months for those with just one risk factor, and 17.6 months for those with two or more (hazard ratio, 1.68; 95% confidence interval, 1.10-2.57; P = .01), suggesting the procedure was “detrimental” to perform in the presence of multiple risk factors, the investigator said.
By contrast, among patients treated with sunitinib alone, there was no significant difference in median overall survival for patients with one risk factor versus those with two or more risk factors, said Dr. Méjean, who is with the Hôpital Européen Georges-Pompidou and Paris Descartes University.
In another analysis of the data, delayed nephrectomy after initial systemic therapy was associated with long overall survival in good responders, supporting that approach as a “good therapeutic strategy,” he said.
Based on these results, Dr. Méjean told ASCO attendees he would “go back to the operating theater to operate just very selected patients.”
In a podium discussion,, said CARMENA makes it “undeniable” that up-front cytoreductive therapy should be applied to a “very select group” of patients.
While that select group may be defined as the one IMDC risk factor group, Dr. Kutkov said it is also appropriate to offer cytoreductive nephrectomy to carefully selected patients who do not need immediate systemic therapy.
“If the plan is to observe without systemic therapy, proceed with cytoreductive nephrectomy, and for everybody else, I think we take great caution in offering cytoreductive nephrectomy, because it absolutely can harm,” said Dr. Kutikov, professor and chief of urologic oncology at Fox Chase Cancer Center, Philadelphia.
The CARMENA update confirmed that, in general, cytoreductive nephrectomy should not be the standard of care, according to Dr. Méjean.
With follow-up of 61.5 months, or longer than what wasfor the 450-patient trial, cytoreductive nephrectomy followed by sunitinib was again found to be not superior to sunitinib alone, he said. Median overall survival was 15.6 months for the nephrectomy plus sunitinib arm versus 19.8 months for the sunitinib arm, showing that sunitinib alone was noninferior based on the statistical design of the trial (hazard ratio, 0.97; 95% CI, 0.79-1.19, with a fixed upper limit for noninferiority of 1.20).
Dr. Méjean reported disclosures related to Ipsen, Novartis, Pfizer, Bristol-Myers Squibb, Janssen, Sanofi and Roche.
SOURCE: Méjean A et al. ASCO 2019, .