What “approved” means
A medicine is not approved generically “against melanoma”: authorisation concerns an indication, a population and sometimes a specific combination. Stage, mutation, previous treatment and age may define its use. European authorisation and reimbursement by Italy’s national health service are separate steps; the treating centre must check the applicable AIFA conditions.
This page provides relevant examples for cutaneous melanoma, not a complete catalogue of every cancer indication. Its earlier version mainly listed US authorisations and historical brands: that picture did not adequately represent current choices in Italy. A brand identifies a product, not a treatment that is necessarily better than the alternatives.
Sources for this section: AIFA — Reimbursement and pricing; ESMO — Cutaneous melanoma: Clinical Practice Guideline (2024/2025).
Established immunotherapies with different indications
Pembrolizumab and nivolumab are anti-PD-1 medicines used in defined advanced-disease and adjuvant settings. Not every stage requires medication after surgery. Assessment considers recurrence risk, expected benefit and potential immune toxicities, including persistent effects.
Ipilimumab targets CTLA-4 and may be used alone or with nivolumab according to the indication and clinical assessment. The combination is not simply the sum of two monotherapies and needs careful toxicity management. Nivolumab with relatlimab, marketed as Opdualag, has a European Union first-line indication in advanced melanoma with tumour PD-L1 expression below 1%, in adults and adolescents aged 12 or older. This European restriction must not be omitted.
Sources for this section: EMA — Keytruda: indications and product information; EMA — Opdivo: indications and product information; EMA — Yervoy: indications, product information and leaflet; EMA — Opdualag: indications and product information; AIFA — Opdualag: reimbursement determination 466/2024.
Targeted treatments require the relevant target
For melanoma with a BRAF V600 mutation, BRAF/MEK combinations include dabrafenib–trametinib, vemurafenib–cobimetinib and encorafenib–binimetinib for advanced disease under their respective indications. Their components cannot be freely exchanged. Mutation positivity must be established by a validated test on tumour material.
Dabrafenib with trametinib also has an adjuvant indication in completely resected BRAF V600 stage III melanoma. This does not automatically extend to the other combinations. The variant report and clinical setting require specialist interpretation; having BRAF V600E does not necessarily mean targeted therapy should be preferred over immunotherapy.
Sources for this section: EMA — Tafinlar: indications, product information and leaflet; EMA — Mekinist: indications, product information and leaflet; EMA — Cotellic: indications, product information and leaflet; EMA — Zelboraf: indications, product information and leaflet; EMA — Braftovi (encorafenib); ESMO — Cutaneous melanoma: Clinical Practice Guideline (2024/2025).
Selected options and Italian access pathways
Talimogene laherparepvec, or T-VEC/Imlygic, is an intralesional treatment authorised in Europe for specific unresectable melanomas without visceral metastases: it is not a general solution for all metastatic disease. Chemotherapy now has a narrower role than modern approaches and remains an individualised option in selected circumstances.
A use outside the usual indication may nevertheless have substantial evidence and a specific national access pathway. One example is neoadjuvant nivolumab–ipilimumab under AIFA’s determination of 17 November 2025 through Law 648/1996. “Off-label”, “reimbursed through a dedicated pathway” and “experimental” are not synonyms: the situation must be stated explicitly.
Sources for this section: EMA — Imlygic (talimogene laherparepvec); National Cancer Institute — Melanoma Treatment (PDQ), health professional version; AIFA — Nivolumab + ipilimumab, neoadjuvant treatment, Law 648/1996 (17 November 2025).
Overseas approvals and experimental treatments
Lifileucel, a tumour-infiltrating lymphocyte therapy, received accelerated FDA approval in the United States. Amtagvi’s European marketing-authorisation application was withdrawn in 2025: withdrawal of an application must not be confused with withdrawal of an authorisation already granted, nor should this be presented as a routinely available Italian standard.
Personalised neoantigen vaccines and new immunotherapy combinations are being studied. INTerpath-001 records a phase III trial of V940 with pembrolizumab; registry listing does not establish definitive efficacy or access at a particular centre. Participation requires eligibility assessment, informed consent and discussion of alternatives. Do not stop or delay treatment in pursuit of something advertised as “innovative”.
Sources for this section: FDA — Amtagvi (lifileucel), accelerated approval; EMA — Amtagvi: withdrawal of marketing-authorisation application (2025); ClinicalTrials.gov — INTerpath-001, NCT05933577, phase 3; National Cancer Institute — Participate in Cancer Treatment Trials.
Sources and update
- AIFA — Reimbursement and pricing
- ESMO — Cutaneous melanoma: Clinical Practice Guideline (2024/2025)
- EMA — Keytruda: indications and product information
- EMA — Opdivo: indications and product information
- EMA — Yervoy: indications, product information and leaflet
- EMA — Opdualag: indications and product information
- AIFA — Opdualag: reimbursement determination 466/2024
- EMA — Tafinlar: indications, product information and leaflet
- EMA — Mekinist: indications, product information and leaflet
- EMA — Cotellic: indications, product information and leaflet
- EMA — Zelboraf: indications, product information and leaflet
- EMA — Braftovi (encorafenib)
- EMA — Imlygic (talimogene laherparepvec)
- National Cancer Institute — Melanoma Treatment (PDQ), health professional version
- AIFA — Nivolumab + ipilimumab, neoadjuvant treatment, Law 648/1996 (17 November 2025)
- FDA — Amtagvi (lifileucel), accelerated approval
- EMA — Amtagvi: withdrawal of marketing-authorisation application (2025)
- ClinicalTrials.gov — INTerpath-001, NCT05933577, phase 3
- National Cancer Institute — Participate in Cancer Treatment Trials
Editorial revision and source consultation: 17 October 2026. Study dates distinguish current evidence from historical documents. This date does not certify specialist clinical review.