Literature DB >> 36197494

Nivolumab versus placebo as adjuvant therapy for resected stage III melanoma: a propensity weighted indirect treatment comparison and number needed to treat analysis for recurrence-free survival and overall survival.

Jeffrey S Weber1, Tayla Poretta2, Brian D Stwalley2, Leon A Sakkal2, Ella X Du3, Travis Wang3, Yan Chen3, Yan Wang3, Keith A Betts3, Alexander N Shoushtari4,5.   

Abstract

BACKGROUND: Recurrence-free survival (RFS) and overall survival (OS) data for adjuvant nivolumab versus placebo (proxy for routine surveillance) in patients with high-risk, resected melanoma are lacking. This post hoc, indirect treatment comparison (ITC) used pooled data from the phase 3 EORTC 18,071 (ipilimumab vs. placebo) and CheckMate 238 (nivolumab vs. ipilimumab) trials to assess RFS and OS with nivolumab versus placebo and the numbers needed to treat (NNT) over 4 years.
METHODS: Patients with resected stage IIIB-C cutaneous melanoma (American Joint Committee on Cancer seventh edition) were included. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics. RFS NNTs were calculated for nivolumab versus ipilimumab and placebo. OS NNTs were calculated for nivolumab versus placebo. To adjust for different post-recurrence treatments, the difference in post-recurrence survival between the two ipilimumab arms was added to OS of the placebo arm.
RESULTS: This ITC included 278, 643, and 365 patients treated with nivolumab, ipilimumab, and placebo, respectively. Following IPTW, nivolumab was associated with improved RFS versus placebo (hazard ratio [HR]: 0.49; 95% confidence interval [CI] 0.39-0.61) and ipilimumab (HR: 0.69; 95% CI 0.56-0.85). RFS NNT was 4.2 for nivolumab versus placebo and 8.9 for nivolumab versus ipilimumab. After post-recurrence survival adjustment, weighted 4-year OS rates were 75.8% for nivolumab and 64.1% for placebo; OS NNT for nivolumab versus placebo was 8.5.
CONCLUSIONS: In patients with resected stage IIIB-C cutaneous melanoma in this ITC, nivolumab improved RFS versus placebo and ipilimumab, and OS versus placebo after post-recurrence survival adjustment.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Entities:  

Keywords:  Adjuvant therapy; Melanoma; Nivolumab; Overall survival; Routine surveillance

Year:  2022        PMID: 36197494     DOI: 10.1007/s00262-022-03302-5

Source DB:  PubMed          Journal:  Cancer Immunol Immunother        ISSN: 0340-7004            Impact factor:   6.630


  22 in total

1.  Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial.

Authors:  Alexander M M Eggermont; Vanna Chiarion-Sileni; Jean-Jacques Grob; Reinhard Dummer; Jedd D Wolchok; Henrik Schmidt; Omid Hamid; Caroline Robert; Paolo A Ascierto; Jon M Richards; Céleste Lebbé; Virginia Ferraresi; Michael Smylie; Jeffrey S Weber; Michele Maio; Cyril Konto; Axel Hoos; Veerle de Pril; Ravichandra Karra Gurunath; Gaetan de Schaetzen; Stefan Suciu; Alessandro Testori
Journal:  Lancet Oncol       Date:  2015-03-31       Impact factor: 41.316

2.  Adjuvant Pembrolizumab in Resected Stage III Melanoma.

Authors:  Alexander M M Eggermont; Caroline Robert; Stefan Suciu
Journal:  N Engl J Med       Date:  2018-08-09       Impact factor: 91.245

3.  Adjuvant Therapy in the Treatment of Melanoma.

Authors:  Danielle M Bello; Charlotte E Ariyan
Journal:  Ann Surg Oncol       Date:  2018-02-21       Impact factor: 5.344

Review 4.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

Authors:  C M Balch; A C Buzaid; S J Soong; M B Atkins; N Cascinelli; D G Coit; I D Fleming; J E Gershenwald; A Houghton; J M Kirkwood; K M McMasters; M F Mihm; D L Morton; D S Reintgen; M I Ross; A Sober; J A Thompson; J F Thompson
Journal:  J Clin Oncol       Date:  2001-08-15       Impact factor: 44.544

Review 5.  Adjuvant Therapy for Melanoma.

Authors:  Aya Agha; Ahmad A Tarhini
Journal:  Curr Oncol Rep       Date:  2017-05       Impact factor: 5.075

6.  Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy.

Authors:  Alexander M M Eggermont; Vanna Chiarion-Sileni; Jean-Jacques Grob; Reinhard Dummer; Jedd D Wolchok; Henrik Schmidt; Omid Hamid; Caroline Robert; Paolo A Ascierto; Jon M Richards; Céleste Lebbé; Virginia Ferraresi; Michael Smylie; Jeffrey S Weber; Michele Maio; Lars Bastholt; Laurent Mortier; Luc Thomas; Saad Tahir; Axel Hauschild; Jessica C Hassel; F Stephen Hodi; Corina Taitt; Veerle de Pril; Gaetan de Schaetzen; Stefan Suciu; Alessandro Testori
Journal:  N Engl J Med       Date:  2016-10-07       Impact factor: 91.245

7.  Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

Authors:  Jeffrey Weber; Mario Mandala; Michele Del Vecchio; Helen J Gogas; Ana M Arance; C Lance Cowey; Stéphane Dalle; Michael Schenker; Vanna Chiarion-Sileni; Ivan Marquez-Rodas; Jean-Jacques Grob; Marcus O Butler; Mark R Middleton; Michele Maio; Victoria Atkinson; Paola Queirolo; Rene Gonzalez; Ragini R Kudchadkar; Michael Smylie; Nicolas Meyer; Laurent Mortier; Michael B Atkins; Georgina V Long; Shailender Bhatia; Celeste Lebbé; Piotr Rutkowski; Kenji Yokota; Naoya Yamazaki; Tae M Kim; Veerle de Pril; Javier Sabater; Anila Qureshi; James Larkin; Paolo A Ascierto
Journal:  N Engl J Med       Date:  2017-09-10       Impact factor: 91.245

8.  Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

Authors:  Georgina V Long; Axel Hauschild; Mario Santinami; Victoria Atkinson; Mario Mandalà; Vanna Chiarion-Sileni; James Larkin; Marta Nyakas; Caroline Dutriaux; Andrew Haydon; Caroline Robert; Laurent Mortier; Jacob Schachter; Dirk Schadendorf; Thierry Lesimple; Ruth Plummer; Ran Ji; Pingkuan Zhang; Bijoyesh Mookerjee; Jeff Legos; Richard Kefford; Reinhard Dummer; John M Kirkwood
Journal:  N Engl J Med       Date:  2017-09-10       Impact factor: 91.245

Review 9.  Adjuvant Therapy of Melanoma.

Authors:  Ahmad A Tarhini
Journal:  Hematol Oncol Clin North Am       Date:  2020-10-26       Impact factor: 3.722

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