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Mini Oral - Melanoma and other skin tumours

1081MO - Efficacy of ipilimumab plus nivolumab or ipilimumab plus fotemustine vs fotemustine in patients with melanoma metastatic to the brain: Primary analysis of the phase III NIBIT-M2 trial


18 Sep 2020


Mini Oral - Melanoma and other skin tumours



Tumour Site



Anna Di Giacomo


Annals of Oncology (2020) 31 (suppl_4): S672-S710. 10.1016/annonc/annonc280


A.M. Di Giacomo1, V. Chiarion Sileni2, M. Del Vecchio3, P.F. Ferrucci4, M. Guida5, P. Quaglino6, M. Guidoboni7, P. Marchetti8, O. Cutaia1, G. Amato1, E. Gambale1, L. Calabrò1, M. Valente1, R. Danielli1, D. Giannarelli9, M. Mandala10, M. Maio1

Author affiliations

  • 1 Center For Immuno-oncology, University Hospital of Siena, 53100 - Siena/IT
  • 2 Melanoma Cancer Unit, Department Of Experimental & Clinical Oncology, Veneto Oncology Institute-IRCCS, Padova/IT
  • 3 Unit Of Melanoma Medical Oncology, Department Of Medical Oncology And Hematology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 4 Cancer Biotherapy Unit, Department Of Experimental Oncology, European Institute of Oncology, IRCCS, 20141 - Milan/IT
  • 5 Unit Melanoma And Rare Tumors, IRCCS Istituto Tumori Giovanni Paolo II, 70124 - Bari/IT
  • 6 Dermatologic Clinic, Department Of Medical Sciences,, University of Turin, Torino/IT
  • 7 Immunotherapy And Cell Therapy Unit, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 8 Department Of Radiological, Oncological And Pathological Sciences, Sapienza University of Rome, 00189 - Rome/IT
  • 9 Unità Di Biostatistica, IFO- Istituto Nazionale Tumori Regina Elena, 00181 - Rome/IT
  • 10 Oncology And Hematology Dept., Azienda Ospedaliera Papa Giovanni XXIII, 24127 - Bergamo/IT


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Abstract 1081MO


Brain metastases (BM) represent a high-unmet medical need, in which the therapeutic potential of immune-checkpoint(s) (ICI) is being actively investigated. Temozolomide and fotemustine (FTM) have been the therapeutic mainstay of melanoma (MM) patients (pts) with BM for over two decades. The Italian Network for Tumor Biotherapy (NIBIT)-M1 trial firstly demostrated signs of activity of ipilimumab (Ipi) combined with FTM in a subset of 20 MM pts with active BM (Di Giacomo, Lancet Oncol, 2012), with a 3-year survival rate of 28% (Di Giacomo, Annals Oncol, 2015). Two subsequent phase II studies reported the efficacy of Ipi combined with nivolumab (Nivo) in MM pts with asymptomatic BM (Twabi, NEJM 2018; Long, Lancet Oncol 2018). We here report the results of the primary analysis of the NIBIT-M2 study, the first phase III trial that explored the efficacy of Ipi plus Nivo in MM pts with BM.


The NIBIT-M2 is a phase III, multicenter, open-label study in MM pts with active, untreated, and asymptomatic BM. BRAF wilde type or mutant pts were randomized to receive FTM (ARM A), the combination of Ipi and FTM (ARM B), or the combination of Ipi and Nivo (ARM C). Primary objective was overall survival (OS); among secondary were intracranial (i) objective response rate (iORR), i disease control rate (iDCR), and progression free survival (PFS).


From January 2013 to September 2018, 96 MM pts were enrolled, 80 randomized, and 76 were treated: 23 in ARM A, 26 in ARM B, and 27 in ARM C. With a median follow-up of 39 months (mo), median OS was 8.5 mo (CI, 95%: 4.8-12.2) for ARM A, 8.2 mo (CI, 95%: 2.0-14.3) for ARM B, and 29.2 mo (CI, 95%: not yet evaluable) for ARM C. The iORR was 0%, 19.2% and 44.4% in ARM A, B, and C, respectively. The iDCR was 26.1%, 34.6% and 55.6% in ARM A, B, and C, respectively. Median PFS was 3.0 mo (CI, 95%: 2.3-3.6), 3.3 mo (CI, 95%: 1.2-5.4), and 8.4 mo (CI,95%: 4.2-12.7), in ARM A, B, and C, respectively.


Unlike Ipi plus FTM, Ipi plus Nivo significantly (p=0.009) improves the long-term survival of MM pts with BM, compared to FTM. Ipi plus Nivo should represent the treatment of choice in first line MM pts with BM.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

NIBIT Foundation.


Bristol-Myers Squibb.


A.M. Di Giacomo: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: GSK; Advisory/Consultancy: Sanofi. V. Chiarion Sileni: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses, Educational Activities: Pierre Fabre; Honoraria (self), Educational Activities: Merck Serono; Honoraria (self), Educational Activities: Novartis. M. Del Vecchio: Advisory/Consultancy: Novartis; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. P.F. Ferrucci: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre. M. Guida: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD. P. Quaglino: Honoraria (self), Advisory/Consultancy, Educational Activities: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Educational Activities: MSD; Honoraria (self), Advisory/Consultancy, Educational Activities: Novartis; Honoraria (self), Advisory/Consultancy, Educational Activities: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Educational Activities: Igea; Honoraria (self), Advisory/Consultancy, Educational Activities: Roche. M. Guidoboni: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Research grant/Funding (self): MSD. P. Marchetti: Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Boehringer; Research grant/Funding (self): Celgene. L. Calabrò: Advisory/Consultancy: MSD; Advisory/Consultancy: Bristol-Myers Squibb. R. Danielli: Advisory/Consultancy: Merck Serono. M. Mandala: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Research grant/Funding (self): Roche. M. Maio: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Alfasigma. All other authors have declared no conflicts of interest.

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