1084MO - Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial

Background

The phase III NIBIT-M2 study showed a 41% 5-year overall survival (OS) of melanoma patients (pts) with asymptomatic brain metastases (BM) treated with ipilimumab (I) plus nivolumab (N) (I+N) ( Di Giacomo AM, CCR 2021 ). In spite of the significant efficacy of I combined with N, no data are available on long-term survival, and patient-reported outcomes (PROs) and quality of life (QoL) in this patient population. Here, we report the 7-year efficacy outcomes and HRQoL analyses of the NIBIT-M2 study.

Methods

The NIBIT-M2 study recruited melanoma pts with active, untreated, asymptomatic BM from 9 Italian Centers that were randomized (1:1:1) to fotemustine (F) (Arm A), I+F (Arm B), or I+N (Arm C). Primary endpoint was OS; among secondary endpoints were intracranial progression-free survival (iPFS) and HRQoL. PROs were assessed at week (W) 1 and W12 using the EORTC Quality of Life Questionnaire (QLQ)-C30 Version 3.

Results

From Jan 2013 to Sept 2018 , 80 pts were enrolled: 76 received F (23), I+F (26), or I+N (27). As of May 1, 2023, at a median follow-up of 67 months (mo), median OS was 8.5 (95% CI: 6.6-10.3), 8.2 (95% CI: 2.1-14.3) and 29.2 (95% CI: 0-69.9) mo for Arm A, B, and C respectively. The 7-y OS rate was 10.0% (95% CI: 0-22.5) in Arm A, 10.3% (95% CI: 0-22.6) in Arm B, and 42.8% (95% CI: 23.4-62.2) in Arm C. Median iPFS was 3.0 (95% CI: 2.3-3.6), 3.3 (95%CI: 1.2-5.4) and 8.7 (95% CI: 0-19.9) for Arm A, B, and C, respectively. The 7-year iPFS rate was 4.3% (95% CI: 0-12.7) in Arm A, 7.7% (95% CI: 0-17.9) in Arm B, and 28.6% (95% CI: 11.2-46.0) in Arm C. Seventy-two pts (compliance 95%) and 34 pts (compliance 45%) completed the baseline and the W12 QLQ C-30 assessment. HRQoL was preserved in all treatment arms; no significant differences were observed in global health score. Most functional scales evaluated were preserved from baseline to W12, with a lower mean score decrease in pts receiving I+N.

Conclusions

The 7-year results of the NIBIT-M2 study, with the longest follow-up available to date in melanoma pts with asymptomatic BM treated with I+N, continue to show persistent therapeutic efficacy. HRQoL was preserved in all treatment arms and I+N induced a lower decrease in mean functional scales.

Clinical trial identification

NCT02460068.

Editorial acknowledgement

Legal entity responsible for the study

NIBIT Foundation ONLUS.

Funding

Bristol Myers Squibb.

Disclosure

A.M. Di Giacomo: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: Sanofi. V. Chiarion Sileni: Financial Interests, Personal, Advisory Board, analysis of treatment modality (diagnosis, stanging, surgery, radiotherapy, systemic therapy for Merkel cell carcinoma in Italy: Merck-Serono; Financial Interests, Institutional, Invited Speaker, Treatment option for BRAF mutated melanoma: Novartis; Financial Interests, Institutional, Invited Speaker, Treatment choices for BRAF mutated melanoma, evidence-based, and biologically supported: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, Immunotherapy for melanoma treatment present and future: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, registration, and accommodation to attend ASCO annual meetings: Pierre Fabre. M. Del Vecchio: Financial Interests, Personal, Advisory Board: BMS, MSD, Sanofi, Pierre Fabre, Novartis. P.F. Ferrucci: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, MSD, Novartis. M. Guida: Financial Interests, Personal, Advisory Board: Bristol Meyer Squibb, Novartis, Merck Sharp & Dohme. P. Quaglino: Non-Financial Interests, Personal, Advisory Board: BMS, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, MSD. M. Guidoboni: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme. P. Marchetti: Other, Personal, Advisory Board: BMS, Roche, MSD, Novartis, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pfizer, Merck Sharp & Dohme, AstraZeneca, Boehringer Ingelheim, Celgene, Roche. A. Covre: Other, Personal, Advisory Board: EpiGen Therapeutics srl. R. Camerini: Financial Interests, Personal, Advisory Board: Bristol Meyer Squibb; Other, Personal, Advisory Board: Reithera srl, Alfasigma SPA, Cosmo Nbv, EpiGen Therapeutics. L. Calabro: Other, Personal, Advisory Board: BMS, AstraZeneca, MSD, Sanofi, Roche. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. D. Giannarelli: Financial Interests, Personal, Other, Educational Course in Biostatistics: Amgen; Financial Interests, Personal, Other, Course on GRADE system in Hematology: AstraZeneca. M. Maio: Financial Interests, Personal, Advisory Board: BMS, Roche, GSK, Sanofi, Alfasigma, Amgen, Sciclone, Eli Lilly, MSD, Incyte, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Stocks/Shares: EpiGen, Theravance. All other authors have declared no conflicts of interest.