Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Updated results from a phase 3 trial (CheckMate 238)


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Jeffrey S. Weber1,Mario Mandala2,Michele Del Vecchio3,Helen Gogas4,Ana M. Arance5,C. Lance Cowey6,Stéphane Dalle7,Michael Schenker8,Vanna Chiarion-Sileni9,Ivan Marquez-Rodas10,Jean-Jacques Grob11,Marcus Butler12,Mark R. Middleton13,Michele Maio14,Victoria Atkinson15,Reinhard Dummer16,Veerle de Pril17,Anila Qureshi17,James Larkin18,Paolo A. Ascierto19
1NYU Perlmutter Cancer Center,2Papa Giovanni XXIII Hospital,3Medical Oncology, National Cancer Institute,4University of Athens,5Hospital Clinic de Barcelona,,6Texas Oncology–Baylor Charles A. Sammons Cancer Center,7Hospices Civils de Lyon,8Oncology Center Sf Nectarie Ltd.,9Oncology Institute of Veneto IRCCS,10Hospital Gregorio Marañón,,11Hôpital de la Timone,12Princess Margaret Cancer Centre,13Churchill Hospital,14Center for Immuno-Oncology, University Hospital of Siena,15Gallipoli Medical Research Foundation and University of Queensland,16University Hospital of Zurich,17Bristol-Myers Squibb,18The Royal Marsden NHS Foundation Trust,19Istituto Nazionale Tumori Fondazione Pascale

Abstract

Background

Previously, at 18 months' minimum follow-up, nivolumab demonstrated significantly longer recurrence-free survival (RFS) vs ipilimumab in patients with resected stage III/IV melanoma in the phase 3 CheckMate 238 trial. Here, we report updated 24-month efficacy results.

Method

Eligible patients included those ≥15 years of age who underwent complete resection of stage IIIB/C or IV melanoma. 906 patients were randomized 1:1 (stratified by disease stage and 5% PD-L1 expression status) to receive nivolumab 3 mg/kg Q2W (N=453) or ipilimumab 10 mg/kg Q3W for 4 doses, then Q12W (N=453) for up to 1 year, or until disease recurrence or unacceptable toxicity. The primary endpoint was RFS with an exploratory endpoint of distant metastasis-free survival (DMFS).

Results

At 24 months' follow-up, RFS remained significantly longer for nivolumab vs ipilimumab (hazard ratio 0.66, P<0.0001), with 171/453 vs 221/453 events, respectively. The patient subgroup 24-month RFS rates were higher for nivolumab vs ipilimumab (Table). DMFS remained significantly longer for nivolumab vs ipilimumab; 24-month rates were 70.5% and 63.7%, respectively (hazard ratio 0.76, P=0.034).

 

 

Nivolumab

Ipilimumab

RFS, 24-month rates; % (N)

 

 

       ITT

            62.6% (453)

            50.2% (453)

       Stage IIIB

            70.8% (165)

            60.7% (148)

       Stage IIIC

            58.0% (203)

            45.4% (218)

       Stage IV

            58.0% (82)

            44.3% (87)

       PD-L1 ≥5%

            75.5% (152)

            58.4% (154)

       PD-L1 <5%

            55.2% (275)

            45.5% (286)

       BRAF mutant

            61.9% (187)

            51.7% (194)

       BRAF wild-type

            63.5% (197)

            46.2% (212)

Conclusion

With extended follow-up, nivolumab demonstrated sustained efficacy benefit vs ipilimumab in patients with resected stage III/IV melanoma at high risk of recurrence, regardless of disease stage, PD-L1 expression, or BRAF mutation status. These results have been previously presented at the American Society for Clinical Oncology (ASCO) Annual Meeting, June 1-5, 2018, Chicago, IL, USA, and published in the conference proceedings (Abstract 9502).

This study was funded by Bristol-Myers Squibb. Medical writing assistance was provided by StemScientific.