Radical metastasectomy followed by sorafenib versus observation in patients withclear cell renal cell carcinoma: extended follow -up of efficacy results from the randomized phase II RESORT trial

ABSTRACT

Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data.

Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint.

Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis . At a median follow-up of 42 months (interquartile range 31–58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42–76%) at 24 and 44% (95% CI 30–65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34–71%) at 24 and 32% (95% CI 18–57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72–2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site.

Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480

KEYWORDS:

• Metastatic renal cell carcinoma
• surgical metastasectomy
• sorafenib
• relapse-free survival
• adjuvant treatment
• targeted therapy

Article highlights

• After a follow-up of 42 months, metastasectomy followed by sorafenib does not show a prolonged relapse free survival compared with observation in the phase II RESORT trial.

• In oligometastatic disease, surgery can improve survival and delay systemic therapy in selected patients.

• Relapse free survival curves in the whole population are similar according to the interval between nephrectomy and metastasis resection (≤12 versus >12 months)

• The site of disease relapse is independent of the site of the resected lesion.

• At a median follow-up of 42 months, 47% of the patients in the observation arm are still disease free.

Acknowledgments

Trial registration number: NCT01444807

Author contributions

G Procopio and E Verzoni planned the study. A Mennitto wrote the manuscript with the contribution of G Procopio and E Verzoni. R Miceli performed the statistical plan, extracted the data and assessed the statistical analyses. M Claps, V Guadalupi, P Sepe, and F de Braud critically reviewed and edited the manuscript. M Claps, E Verzoni, F Cognetti, A Mosca, VE Chiuri, A Bearz, F Morelli, C Ortega, F Atzori, M Donini recruited patients. V Cappelletti provided technical support. All authors have approved the final manuscript and consented to its publication.

Declaration of interest

G Procopio declares receiving honoraria for the advisory board from Bayer, Bristol Myers Squibb, Ipsen, Merck, Novartis, and Pfizer. E Verzoni declares receiving honoraria for the advisory board from Pfizer, Bristol Myers Squibb, Ipsen, and EUSA pharm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.