Eligible pts with previously untreated unresectable stage III or IV melanoma were randomly assigned in a 1:1:1 ratio and stratified by PD-L1 status, BRAF mutation status, and metastasis stage....With a minimum follow-up of 6.5 y, median OS was 72.1 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI (table)....We observed improvement in OS, PFS, and ORR with NIVO + IPI over NIVO alone.

Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.

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)....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.

...-Known BRAF V600 mutation status. ...

...Subjects must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutionalstandards during the Screening Period.9. ...

...A multidisciplinary discussion withinsurgical oncologists, medical oncologists, and radiologist will assess if disease isresectable.· Signed Written Informed Consent.· Patients must be willing and able to comply with scheduled visits, treatment schedule,laboratory tests and all protocol procedures.· Males and Females, ages =18 years of age.· Eastern Cooperative Oncology Group (ECOG) performance status of 0-1· Have measurable disease based on RECIST 1.1.· Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumorlesion at baseline and at the time points specified in the Study Procedure Tables.· Known BRAF V600 mutation status as determined by local institutional standard. ...

...The BRAF mutation status must be available prior to randomisation....

...BRAF-mutant can be included only if they have been treated with, or developed toxicity with or refused to be treated with BRAF-and/or MEK-targeted therapy in front-line 10....

...- Known BRAF V600 mutation status as determined by an FDA-approved test....

...- Known BRAF V600 mutation status or consent to BRAF V600 mutation testing...

...- BRAF status wild type or mutated (and in that case previous treatment with BRAF inhibitor and MEK inhibitor allowed)...

...The BRAF mutation status must be available prior to randomisation.5. ...

...- BRAF mutations status...

...- For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors...

...- Patients with BRAF V600 mutant melanoma must have previously received BRAF targeted therapy for metastatic melanoma and later experienced disease progression....

...- BRAF-mutation status, locally assessed, should be known (previous BRAF-targeted therapy is allowed)....

...- BRAF-mutant melanoma: prior therapies include BRAF/MEK inhibitors -...

Patients who recurred at distant sites following adjuvant TT showed favorable response rates (42.9%) after switching to first-line treatment (1L) with Ipilimumab+Nivolumab (IPI+Nivo)...In this real-world cohort study we demonstrate that BRAFmut melanoma patients who developed DM upon adjuvant therapy achieve favorable tumor control and prolonged PFS after switching treatment modalities in the first-line setting of stage IV disease.

A total of 291 adults were identified. The median age was 53 years, 42.5% of pts were female, 47% were BRAF-mutated...The objective response rate (ORR) was 39%, with 7.8% of pts achieving a complete response...This real-world study confirms the high efficacy of NIVO+IPI in real-world settings with grade 3/4 toxicity lower than observed in clinical trials. Maintenance of NIVO despite early toxicity during combination treatment appears to have a beneficial effect on patient survival.

In multivariable analysis, BRAF-mutant melanoma was significantly associated with a lower risk of progression or death in the ipilimumab-nivolumab cohort….Ipilimumab-nivolumab–treated patients with BRAF-mutant melanoma display improved PFS and OS compared with patients with NRAS-mutant and double wild-type melanoma.

Advanced BRAF-mutant melanoma patients treated with 1L CPI or TT were selected from a real-world, electronic health record-derived database....CPI was associated with improved survival after adjustment for potential confounders (hazard ratio, 0.75 [95% CI, 0.66–0.87])....This real-world study demonstrated a survival benefit with 1L CPI versus TT.

From that same TMB cutoff, a Cox multivariate analysis stratified by median TMB revealed that mutations in STK11 (HR 2.95; p<0.0007) and TP53 (HR 1.89; p<0.0032) were associated with a higher risk of death. Otherwise, mutations in TERT (HR 0.54; p<0.0044) and NOTCH3 (HR 0.23; p<0.0355) were protective.... the mutational profile can contribute to define outcomes to ICIs.

Patients received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction) followed by nivolumab 3 mg/kg every 2 weeks (maintenance) until progression or unacceptable toxicity or a maximum of 48 weeks...Twenty-four-month OS rates were 63% in patients aged ≥75 years, 56% in patients with elevated lactate dehydrogenase levels, 73% in patients with BRAF wild-type tumors, 70% in patients with BRAF mutant tumors, and 56% in patients with mucosal melanoma. In this EAP, nivolumab plus ipilimumab demonstrated high survival rates and safety outcomes consistent with those from randomized clinical trials...

Patients with BRAF-mutant melanoma were eligible and included in the analysis, among whom 107 (19%) received first-line nivolumab plus ipilimumab, 227 (41%) received BRAF plus MEK inhibitors and 223 (40%) received other treatment as the index therapy….In this real-world study, patients treated with first-line NIVO + IPI showed significant survival benefit versus those receiving first-line BRAFi + MEKi.