Key points
- Melanoma accounts for about 1% of skin cancers, but it causes most skin cancer deaths [1].
- The most important preventable risk factor is ultraviolet (UV) radiation from the sun and from tanning devices [2].
- Early-stage melanoma is treated well with surgery, so pay attention to any new or changing mole.
- Immunotherapy (especially anti-PD-1 drugs such as pembrolizumab and nivolumab) and BRAF/MEK targeted therapy have dramatically improved survival in people with advanced melanoma [3, 4, 21].
- Immunotherapy before surgery (neoadjuvant), such as pembrolizumab given before and after surgery, has produced better results in stage III melanoma than treatment given only after surgery [5, 6].
What is melanoma?
Melanoma is a cancer that arises from melanocytes, the cells that make the skin’s pigment. Its incidence is rising, particularly in white populations, and most cases are linked to exposure to ultraviolet radiation from the sun or from tanning beds; however, some subtypes (such as melanoma of the palms and soles, or mucosal melanoma) are not related to the sun [2].
Melanoma is often dark, but it is sometimes unpigmented (amelanotic) and skin-colored or pink [2]. By comparison, basal cell and squamous cell skin cancers are far more common but rarely cause death [1].
Warning signs: the ABCDE rule
To check moles, dermatologists use the simple ABCDE rule. Any mole with one of these features should be seen by a doctor:
- A — Asymmetry: the two halves of the mole do not match.
- B — Border: irregular edges that are notched, blurred or poorly defined.
- C — Color: uneven color, with several shades of brown, black, red, white or blue in one mole.
- D — Diameter: usually larger than 6 millimeters (the size of a pencil eraser), although melanoma can also be smaller.
- E — Evolving: any change in size, shape or color, or new itching, bleeding or ulceration.
The “ugly duckling” sign is also important: a mole that looks different from the other moles on your body.
In good light and with the help of a mirror, check all of your skin, including the soles of your feet, between your fingers and toes, your back and your scalp. Take photos of suspicious moles so you can see changes more easily. Most moles are harmless, but any new change is worth an examination.
When should I contact my doctor?
Tell your doctor or treatment team without delay about any of the following:
- Skin changes: a new mole or spot; a mole that changes in size, shape or color, or starts to itch, bleed or ulcerate; and a mole that looks different from the other moles on your body (the ABCDE rule).
- During immunotherapy: diarrhea, cough or shortness of breath, skin rash, severe fatigue or an unusual headache [25, 26]. Most of these side effects can be controlled if they are treated early (guide to immunotherapy side effects (Persian)).
- During treatment with dabrafenib and trametinib: a fever of 38 °C or higher [29], or blurred vision, loss of vision or any other change in your eyesight [30].
Risk factors, prevention and screening
Ultraviolet radiation
Repeated sunburns, especially in childhood, and the use of tanning devices (sunbeds) are the most important preventable risk factors [2].
Skin type and moles
Fair skin, blond or red hair, light-colored eyes, a large number of moles or atypical moles, and a personal or family history of melanoma all increase the risk.
Regular sunscreen use
In a randomized trial in Australia, daily sunscreen use was associated with fewer melanomas; the reduction in invasive melanoma was striking (hazard ratio 0.27) [7].
Protective habits
Avoiding the sun during peak hours; wearing long-sleeved clothing, a wide-brimmed hat and sunglasses; and staying away from tanning beds completely.
In 2023 the USPSTF concluded that the evidence is insufficient to recommend for or against routine skin examination of all asymptomatic adults [1]. Nevertheless, people at high risk (a history of melanoma, many or atypical moles, a family history) should talk with their doctor about periodic skin checks.
Diagnosis and staging
Diagnostic pathway for melanoma
- 1
Skin examination and dermoscopy
The doctor examines the lesion with a dermatoscope (a special illuminated magnifier).
- 2
Excisional biopsy
Complete removal of the suspicious lesion with a narrow margin for pathological examination; the diagnosis is based on a combination of clinical and pathological findings [2].
- 3
Pathology report
The most important prognostic factors are tumor thickness (Breslow) and the presence of ulceration. In the eighth edition of the AJCC system, a tumor less than 0.8 mm thick without ulceration is classified as T1a [8].
- 4
Sentinel lymph node biopsy
Performed for thicker tumors to determine whether the lymph nodes are involved; it helps establish the stage and the need for additional treatment [2].
- 5
Imaging and genetic testing
In higher stages, CT or PET-CT and brain MRI, plus testing for a BRAF mutation to select targeted therapy. Stage III is divided by T and N category into four subgroups, IIIA to IIID, and brain metastasis is classified as M1d [8].
Treatment by stage
Treatment options for melanoma
Surgery
The main treatment for early melanoma; the excision margin is determined by the tumor thickness [2].
Immunotherapy
Targeted therapy
| Stage | Main treatment | Additional treatment / notes |
|---|---|---|
| 0 and I | Wide excision of the lesion with a margin appropriate to the tumor thickness [2] | Usually no other treatment is needed; regular skin follow-up. |
| II | Wide excision + sentinel node biopsy [2] | In stages IIB and IIC, adjuvant immunotherapy with pembrolizumab or nivolumab for 12 months reduces the risk of recurrence and can be considered [17, 20]. |
| III, resectable | Neoadjuvant immunotherapy followed by surgery: pembrolizumab before and after surgery [5, 17] or neoadjuvant nivolumab + ipilimumab (the preferred approach in the 2025 ESMO guideline) [6, 17]; or surgery followed by adjuvant therapy | Adjuvant: anti-PD-1 immunotherapy (pembrolizumab or nivolumab) [17, 19] or, with a BRAF V600E mutation, dabrafenib + trametinib [9, 16, 17]. With a positive sentinel node, completion lymph node dissection is usually not needed [10]. |
| III, unresectable, and IV | Single-agent anti-PD-1 immunotherapy (pembrolizumab or nivolumab) [3, 17, 21], or the combination nivolumab + ipilimumab (the ESMO-preferred option when it can be given safely) or nivolumab + relatlimab [3, 17, 22]; with a BRAF mutation, BRAF/MEK inhibitors such as dabrafenib + trametinib are another option [4, 17] | After failure of the first treatment: with a BRAF mutation, BRAF/MEK inhibitors (if not used before); immunotherapy combinations, TIL cell therapy in selected patients [12], or a clinical trial; in later lines, chemotherapy, which has limited efficacy [17]; radiation therapy or surgery for metastases in selected cases. |
Treatment decisions should be made by a multidisciplinary team, taking each patient’s circumstances into account.
Non-melanoma skin cancers: basal cell and squamous cell
Basal cell carcinoma (BCC) is the most common malignant cancer in white people. It usually appears as a shiny, pearly bump or a sore that does not heal, mostly on the face and other sun-exposed areas. The first treatment is complete surgical removal, and for high-risk or recurrent tumors, or those in sensitive areas of the face, surgery with microscopic margin control (such as Mohs surgery) is recommended. For low-risk superficial lesions, topical treatments and photodynamic therapy are options; in advanced cases, hedgehog pathway inhibitors (vismodegib and sonidegib) and, after them, cemiplimab are used [13].
Cutaneous squamous cell carcinoma (cSCC) usually appears as a scaly, wart-like or ulcerated lesion on sun-damaged skin. Most cases are treated with surgery with margin assessment, and radiation therapy is an option for patients who cannot have surgery [24]. In advanced or metastatic disease for which curative surgery or radiation therapy is not possible, anti-PD-1 drugs such as pembrolizumab and cemiplimab are the first-line systemic treatment [14, 18, 24]. In high-risk patients, cemiplimab after surgery and radiation therapy reduced the risk of recurrence or death [15]; according to the 2026 European guideline, the decision about this adjuvant treatment should be made by a multidisciplinary team [24].
What should I do after diagnosis?
Frequently asked questions
Is every dark mole dangerous?
No. Most moles are benign. Moles that have ABCDE features, look different from your other moles or are changing should be checked by a doctor. Full answer: What are the symptoms of skin cancer? (Persian)
Can people with dark skin get melanoma?
Yes. Melanoma is much more common in white people, but in people with darker skin it is often diagnosed later and at more advanced stages [1]. In these people, melanoma may appear on the palms, on the soles of the feet or under a nail.
Does sunscreen really prevent melanoma?
Evidence from a randomized trial shows that regular daily sunscreen use in adults is associated with fewer melanomas, especially invasive melanomas [7]. Sunscreen should be used alongside other protective measures, not instead of them.
Does removing a mole or taking a biopsy make melanoma spread?
No. A biopsy is the main way to make the diagnosis, and complete removal of the suspicious lesion is also the first step of treatment [2].
Has the mRNA melanoma vaccine been approved?
These vaccines are made for each patient based on the genetic changes in that patient’s own tumor. Results of a phase 2b trial have been promising, even at 5-year follow-up [23], but the vaccines are still in clinical trials and have not been approved as standard treatment.
Evidence and recent advances (for physicians)
For physicians
Resectable melanoma: adjuvant and neoadjuvant therapy
Adjuvant pembrolizumab was effective in KEYNOTE-054 (stage III; 7-year RFS 50% vs 36%; HR 0.63) [19] and KEYNOTE-716 (stage IIB/IIC; 48-month RFS 71.3% vs 58.3%; HR 0.62) [20]. However, more recent evidence supports the superiority of starting immunotherapy before surgery: in SWOG S1801, three doses of neoadjuvant pembrolizumab, continued after surgery, improved EFS compared with adjuvant therapy alone (two-year EFS 72% vs 49%) [5]; and in the phase 3 NADINA trial, two cycles of neoadjuvant nivolumab + ipilimumab followed by response-adapted adjuvant therapy improved EFS (12-month EFS 83.7% vs 57.2%; HR 0.32). Overall, 59.0% of patients had a major pathological response, and their 12-month RFS was 95.1%; grade 3 or higher adverse events related to systemic therapy occurred in 29.7% vs 14.7% with adjuvant nivolumab [6]. Accordingly, the 2025 ESMO guideline recommends neoadjuvant immunotherapy (nivolumab + ipilimumab, or pembrolizumab before and after surgery) for resectable stage III melanoma with clinically involved lymph nodes, and allows adjuvant therapy to be omitted in patients with a major pathological response [17]. In addition, MSLT-II showed that immediate completion lymph node dissection for a positive sentinel node does not improve melanoma-specific survival and increases lymphedema from 6.3% to 24.1% [10].
In the adjuvant treatment of stage III disease with a BRAF V600E/K mutation, the COMBI-AD trial (dabrafenib + trametinib) achieved a 5-year RFS of 52% vs 36% (HR 0.51) [9]. In the final analysis, with about 10 years of follow-up, the 20% reduction in the risk of death was not statistically significant (HR 0.80; P=0.06), but a survival benefit was seen in the V600E subgroup (HR 0.75) [16]; for this reason, the 2025 ESMO guideline recommends adjuvant targeted therapy for V600E mutations but not for V600K mutations [17].
In the 5-year report of the phase 2b KEYNOTE-942 trial (157 patients with resected stage IIIB to IV melanoma), the individualized neoantigen therapy mRNA-4157 (intismeran autogene) plus pembrolizumab, compared with pembrolizumab alone, prolonged recurrence-free survival (HR 0.510; 95% CI 0.294 to 0.887) and distant metastasis-free survival (HR 0.411), with a favorable but inconclusive trend in overall survival (HR 0.471; 95% CI 0.165 to 1.345) [23]; these analyses are descriptive, and confirmation requires peer-reviewed publication of the phase 3 trial (INTerpath-001); this treatment is not yet approved and is available only within a clinical trial.
Advanced disease: first line
Single-agent anti-PD-1 drugs are the backbone of first-line treatment. At 10-year follow-up of KEYNOTE-006, pembrolizumab improved overall survival compared with ipilimumab (median 32.7 vs 15.9 months; HR 0.71; 10-year survival 34.0% vs 23.6%), and among patients who completed about 2 years of treatment (at least 94 weeks), 8-year survival was 80.8% [21]. In the final 10-year results of CheckMate 067, median OS was 36.9 months with nivolumab monotherapy vs 19.9 months with ipilimumab, and reached 71.9 months with nivolumab + ipilimumab; median melanoma-specific survival with the combination exceeded 120 months; and among patients who were alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% [3]. Combined LAG-3 and PD-1 blockade with relatlimab + nivolumab in RELATIVITY-047 improved progression-free survival compared with nivolumab alone, with grade 3–4 treatment-related adverse events in 18.9% vs 9.7% [11]; at the 4-year update, 4-year PFS was 30.6% vs 23.6%, and 4-year OS was numerically better (52.0% vs 42.8%; descriptive analysis) [22].
For unresectable disease, the 2025 ESMO guideline recommends first-line nivolumab or pembrolizumab monotherapy (I, A); considers nivolumab + ipilimumab the preferred option for all patients regardless of BRAF status, provided it can be given safely (I, A); and also lists nivolumab + relatlimab as a first-line option (I, B) [17]. In BRAF-mutant melanoma, if anti-PD-1–based therapy is not suitable, a BRAF/MEK combination is a first-line option [17].
In BRAF V600–mutant advanced melanoma, pooled COMBI-d and COMBI-v data showed a 5-year OS of 34% with dabrafenib + trametinib, and of 71% in patients with a complete response [4].
After failure of immunotherapy
Second-line options depend on the first-line treatment: with a BRAF mutation, BRAF/MEK inhibitors; if anti-PD-1 therapy was not given first line (e.g., after targeted therapy), pembrolizumab or nivolumab; and immunotherapy combinations such as nivolumab + ipilimumab, ipilimumab alone or (after failure of anti-PD-1 monotherapy) nivolumab + relatlimab. TIL cell therapy is an intensive option for selected patients. In later lines, when a clinical trial, immunotherapy or BRAF/MEK inhibitors are not possible or appropriate, chemotherapy, which has modest activity and no effect on overall survival, can be used [17].
In the first phase 3 trial of TIL cell therapy in a solid tumor (86% of patients refractory to anti-PD-1), TIL improved progression-free survival compared with ipilimumab (median 7.2 vs 3.1 months; HR 0.50; objective response 49% vs 21%); median OS was 25.8 vs 18.9 months, and all patients in the TIL group had grade 3 or higher adverse events (mainly myelosuppression caused by the conditioning chemotherapy) [12].
Non-melanoma skin cancers: cSCC
In advanced cSCC, pembrolizumab produced responses in 34.3% of patients with recurrent or metastatic disease [18], and cemiplimab produced responses in about half of patients [14]. In the phase 3 C-POST trial (cemiplimab vs placebo after surgery and radiotherapy in high-risk cSCC), 24-month disease-free survival was 87.1% vs 64.1% (HR 0.32) [15].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index20 regimens
These points apply to all of the regimens below that contain these drugs; each regimen’s notes list only what differs.
- Immune checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab, relatlimab and cemiplimab): check liver enzymes, creatinine and thyroid function at baseline and periodically [25, 26, 27, 28, 35]. Dose reduction of pembrolizumab, nivolumab, ipilimumab and cemiplimab is not recommended [25, 26, 27, 35]. Pembrolizumab, nivolumab and cemiplimab: withhold for severe (grade 3) immune-mediated adverse reactions; permanently discontinue for grade 4 reactions, recurrent grade 3 reactions requiring immunosuppression, or inability to taper prednisone to 10 mg per day or less within 12 weeks [25, 26, 35]. Ipilimumab: withhold for severe immune-mediated adverse reactions and permanently discontinue for life-threatening or persistent reactions [27].
- Dabrafenib + trametinib (adjuvant and metastatic disease): take both drugs on an empty stomach (1 hour before or 2 hours after a meal), with dabrafenib doses about 12 hours apart [29, 30]. Fever is common (58% with the combination): at 38 °C (100.4 °F) or higher, withhold both drugs and resume at the same or a lower dose once the fever resolves; evaluate fever accompanied by rigors, hypotension, dehydration or renal failure [29]. Dabrafenib dose reductions: 100, 75, then 50 mg twice daily; trametinib: 1.5, then 1 mg once daily [29, 30]. Ophthalmologic examination for any visual disturbance (within 24 hours for sudden loss of vision) [30].
- All BRAF/MEK combinations (dabrafenib + trametinib and encorafenib + binimetinib): LVEF before starting, after one month and then every 2 to 3 months [30, 32]; skin examination before starting, every 2 months and for up to 6 months after discontinuation [30, 31].
For physicians
Resectable melanoma: neoadjuvant and adjuvant
Neoadjuvant–adjuvant pembrolizumab (SWOG S1801)
Measurable, resectable stage IIIB to IVC melanoma with clinically detectable diseaseCycle length: Every 21 days
Measurable, resectable stage IIIB to IVC melanoma with clinically detectable disease
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Neoadjuvant | |||
| Pembrolizumab | 200 mg | IV, 30-minute infusion | Day 1 every 3 weeks, 3 doses; surgery within 3 weeks afterward |
| Adjuvant | |||
| Pembrolizumab | 200 mg | IV, 30-minute infusion | Day 1 every 3 weeks, 15 doses (starting within 84 days after surgery) |
Doses from the trial [5] and ClinicalTrials.gov NCT03698019.
Evidence: SWOG S1801 (2023)
Neoadjuvant nivolumab + ipilimumab (NADINA)
Resectable stage III melanoma with macroscopic (clinically detectable) lymph node metastases, ECOG 0–1, no prior immunotherapy or BRAF/MEK therapy; preferred approach in ESMO 2025
Resectable stage III melanoma with macroscopic (clinically detectable) lymph node metastases, ECOG 0–1, no prior immunotherapy or BRAF/MEK therapy; preferred approach in ESMO 2025
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Neoadjuvant | |||
| Ipilimumab | 80 mg (flat dose) | IV | Every 3 weeks, 2 cycles |
| Nivolumab | 240 mg | IV | Every 3 weeks, 2 cycles |
| Adjuvant, only for a partial or no pathological response | |||
| Nivolumab | 480 mg | IV | Every 4 weeks, 11 cycles |
Regimen and doses from the trial registration [38] and the publication [6]. The ipilimumab dose in this regimen (80 mg flat) differs from that of the metastatic-disease regimen, and this use is not included in the FDA label [25, 26, 27].
Evidence: NADINA (2024)
Adjuvant pembrolizumab (KEYNOTE-054 and KEYNOTE-716)
Stage IIB, IIC or III melanoma after complete resection (adults and children aged 12 years and older)
Stage IIB, IIC or III melanoma after complete resection (adults and children aged 12 years and older)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg) | IV, 30-minute infusion | Day 1 every 3 weeks (400 mg dose: every 6 weeks) |
Per the FDA label [25]; children aged 12 years and older: 2 mg/kg every 3 weeks (maximum 200 mg) [25]. Evidence: [19, 20].
Evidence: KEYNOTE-716 (2025), KEYNOTE-054 (2024), KEYNOTE-716 (2022)
Adjuvant nivolumab
Stage IIB, IIC, III or IV melanoma after complete resection (adults and children aged 12 years and older weighing 40 kg or more)
Stage IIB, IIC, III or IV melanoma after complete resection (adults and children aged 12 years and older weighing 40 kg or more)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nivolumab | 240 mg (or 480 mg) | IV, 30-minute infusion | Every 2 weeks (480 mg dose: every 4 weeks) |
Adjuvant dabrafenib + trametinib (COMBI-AD)
Stage III melanoma with lymph node involvement and a BRAF V600 mutation after complete resection; ESMO 2025 recommends it only for V600E mutations (not V600K)Cycle length: Continuous
Stage III melanoma with lymph node involvement and a BRAF V600 mutation after complete resection; ESMO 2025 recommends it only for V600E mutations (not V600K)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dabrafenib | 150 mg twice daily | Oral, on an empty stomach | Daily, continuously |
| Trametinib | 2 mg once daily | Oral, on an empty stomach | Daily, continuously |
Evidence: COMBI-AD (2024), COMBI-AD (2020)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Unresectable or metastatic melanoma: first-line immunotherapy
Pembrolizumab monotherapy (KEYNOTE-006)
Unresectable or metastatic melanoma, first line (or after targeted therapy if no prior anti-PD-1 therapy)
Unresectable or metastatic melanoma, first line (or after targeted therapy if no prior anti-PD-1 therapy)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg) | IV, 30-minute infusion | Day 1 every 3 weeks (400 mg dose: every 6 weeks) |
Evidence: KEYNOTE-006 (2024)
Nivolumab monotherapy
Unresectable or metastatic melanoma, first line (or after targeted therapy if no prior anti-PD-1 therapy)
Unresectable or metastatic melanoma, first line (or after targeted therapy if no prior anti-PD-1 therapy)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nivolumab | 240 mg (or 480 mg) | IV, 30-minute infusion | Every 2 weeks (480 mg dose: every 4 weeks) |
Nivolumab + ipilimumab (CheckMate 067)
Unresectable or metastatic melanoma, first line, regardless of BRAF status; the ESMO-preferred option when it can be given safely
Unresectable or metastatic melanoma, first line, regardless of BRAF status; the ESMO-preferred option when it can be given safely
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction | |||
| Nivolumab | 1 mg/kg | IV, 30-minute infusion (nivolumab first, then ipilimumab on the same day) | Day 1 every 3 weeks, 4 doses |
| Ipilimumab | 3 mg/kg | IV, 30-minute infusion | Day 1 every 3 weeks, 4 doses |
| Maintenance | |||
| Nivolumab | 240 mg (or 480 mg) | IV, 30-minute infusion | Every 2 weeks (480 mg dose: every 4 weeks) |
Per the FDA labels [26, 27]; evidence and place in therapy: [3, 17]. Note: the doses are the reverse of the kidney cancer regimen (in melanoma, nivolumab 1 mg/kg and ipilimumab 3 mg/kg). For toxicity, both drugs are withheld or discontinued together [26, 27].
Evidence: CheckMate 067 (2025)
Nivolumab + relatlimab (RELATIVITY-047)
Unresectable or metastatic melanoma, first line (ESMO: I, B); or after failure of anti-PD-1 monotherapyCycle length: Every 28 days
Unresectable or metastatic melanoma, first line (ESMO: I, B); or after failure of anti-PD-1 monotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nivolumab + relatlimab (fixed-dose combination) | 480 mg nivolumab + 160 mg relatlimab | IV, 30-minute infusion | Day 1 every 4 weeks |
Per the FDA label [28]; for adults and children aged 12 years and older weighing at least 40 kg.
Evidence: RELATIVITY-047 (2025), RELATIVITY-047 (2022)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Unresectable or metastatic BRAF V600–mutant melanoma: targeted therapy
Dabrafenib + trametinib (COMBI-d and COMBI-v)
Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation; first line if anti-PD-1–based therapy is not suitable, or after failure of immunotherapyCycle length: Continuous
Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation; first line if anti-PD-1–based therapy is not suitable, or after failure of immunotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dabrafenib | 150 mg twice daily | Oral, on an empty stomach | Daily, continuously |
| Trametinib | 2 mg once daily | Oral, on an empty stomach | Daily, continuously |
Evidence: COMBI-d / COMBI-v (2019)
Encorafenib + binimetinib
Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (alternative BRAF/MEK combination)Cycle length: Continuous
Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (alternative BRAF/MEK combination)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Encorafenib | 450 mg once daily | Oral, with or without food | Daily, continuously |
| Binimetinib | 45 mg twice daily (about 12 hours apart) | Oral, with or without food | Daily, continuously |
Per the FDA labels [31, 32]. Encorafenib dose reductions: 300 mg, then 225 mg; if binimetinib is withheld, give encorafenib at no more than 300 mg [31]. Binimetinib dose reduction: 30 mg twice daily; if encorafenib is permanently discontinued, discontinue binimetinib as well. Liver tests before starting and monthly; CPK and creatinine before starting and periodically; assess visual symptoms at every visit and perform eye examinations at regular intervals [32]; monitor the ECG in patients at risk of QTc prolongation [31].
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Unresectable or metastatic melanoma: later lines
Ipilimumab monotherapy
Later lines (after failure of anti-PD-1 monotherapy), in selected patientsCycle length: Every 21 days
Later lines (after failure of anti-PD-1 monotherapy), in selected patients
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ipilimumab | 3 mg/kg | IV, 30-minute infusion | Day 1 every 3 weeks |
TIL cell therapy (lifileucel; AMTAGVI)
Unresectable or metastatic melanoma after anti-PD-1 therapy and, with a BRAF V600 mutation, after a BRAF inhibitor with or without a MEK inhibitor; selected patients with good performance statusCycle length: Once
Unresectable or metastatic melanoma after anti-PD-1 therapy and, with a BRAF V600 mutation, after a BRAF inhibitor with or without a MEK inhibitor; selected patients with good performance status
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lymphodepletion | |||
| Cyclophosphamide (with mesna) | 60 mg/kg | IV | Daily, 2 days |
| Fludarabine | 25 mg/m² | IV | Daily, 5 days (after cyclophosphamide) |
| Cell infusion | |||
| Lifileucel (autologous TIL) | 7.5×10⁹ to 72×10⁹ viable cells (single dose) | IV | 24 hours to 4 days after the last fludarabine dose |
| After infusion | |||
| Interleukin-2 (aldesleukin) | 600,000 IU/kg | IV | Every 8 to 12 hours, up to 6 doses; starting 3 to 24 hours after the infusion |
Per the FDA label [33]. Administer in a hospital with access to intensive care. Premedication: acetaminophen and an H1 antihistamine about 30 to 60 minutes before the infusion; avoid prophylactic systemic corticosteroids. Boxed warning: treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment; filgrastim from day 1 after the infusion until the ANC is above 1000/µL on 3 consecutive days; antimicrobial prophylaxis per institutional protocol [33]. In the phase 3 trial [12], hospital-manufactured TIL was given after lymphodepletion with cyclophosphamide (2 days) and fludarabine (5 days), together with high-dose interleukin-2.
Evidence: TIL (NKI/CCIT M14TIL) (2022)
Dacarbazine
Later lines, when a clinical trial, immunotherapy or BRAF/MEK therapy is not possible or appropriate; modest activity and no effect on overall survivalCycle length: Every 21 days
Later lines, when a clinical trial, immunotherapy or BRAF/MEK therapy is not possible or appropriate; modest activity and no effect on overall survival
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dacarbazine | 250 mg/m² per day (or 2 to 4.5 mg/kg per day for 10 days, every 4 weeks) | IV | Days 1 to 5 |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Non-melanoma skin cancers: cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC)
Pembrolizumab in advanced cSCC
Recurrent or metastatic cSCC, or locally advanced cSCC not curable by surgery or radiotherapy
Recurrent or metastatic cSCC, or locally advanced cSCC not curable by surgery or radiotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg) | IV, 30-minute infusion | Day 1 every 3 weeks (400 mg dose: every 6 weeks) |
Cemiplimab in advanced cSCC
Metastatic or locally advanced cSCC not amenable to curative surgery or radiotherapyCycle length: Every 21 days
Metastatic or locally advanced cSCC not amenable to curative surgery or radiotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV, 30-minute infusion | Day 1 every 3 weeks |
Evidence: PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma (2018)
Adjuvant cemiplimab (C-POST)
cSCC at high risk of recurrence after surgery and radiotherapy; decision by a multidisciplinary team
cSCC at high risk of recurrence after surgery and radiotherapy; decision by a multidisciplinary team
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Part 1 | |||
| Cemiplimab | 350 mg | IV, 30-minute infusion | Every 3 weeks for 12 weeks |
| Part 2 | |||
| Cemiplimab | 700 mg (or continue 350 mg every 3 weeks) | IV, 30-minute infusion | Every 6 weeks |
Evidence: C-POST (2025)
Vismodegib
Metastatic BCC, or locally advanced BCC that has recurred after surgery or is not suitable for surgery and radiotherapyCycle length: Continuous
Metastatic BCC, or locally advanced BCC that has recurred after surgery or is not suitable for surgery and radiotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Vismodegib | 150 mg once daily | Oral, with or without food | Daily, continuously |
Per the FDA label [36]; place in therapy: [13]. Severe embryo-fetal toxicity: verify pregnancy status within 7 days before starting; no blood donation for 24 months after the last dose. Withhold for up to 8 weeks for intolerable adverse reactions; permanently discontinue for severe cutaneous reactions (SJS, TEN, DRESS) [36].
Sonidegib
Locally advanced BCC that has recurred after surgery or radiotherapy, or is not suitable for themCycle length: Continuous
Locally advanced BCC that has recurred after surgery or radiotherapy, or is not suitable for them
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Sonidegib | 200 mg once daily | Oral, on an empty stomach (1 hour before or 2 hours after a meal) | Daily, continuously |
Per the FDA label [37]; place in therapy: [13]. Serum CK and creatinine before starting, periodically and if muscle symptoms occur; CK more than 10 times the upper limit of normal, or more than 2.5 times with worsening renal function: permanently discontinue. Pregnancy testing before starting; no blood donation for 20 months after the last dose [37].
Cemiplimab in BCC
Locally advanced or metastatic BCC after a hedgehog pathway inhibitor, or when these drugs are not appropriateCycle length: Every 21 days
Locally advanced or metastatic BCC after a hedgehog pathway inhibitor, or when these drugs are not appropriate
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV, 30-minute infusion | Day 1 every 3 weeks |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
13 itemsNeoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma
Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma
Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update
Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma
Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study
Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma
Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma
Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study
Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
Clinical guidelines
1 itemCutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
References
38 referencesShow all references, 22 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 7Reduced Melanoma After Regular Sunscreen Use: Randomized Trial Follow-Up
- 8Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual
- 9
- 10Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma
- 11Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
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- 34Dacarbazine for injection: Prescribing Information
- 35
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- 37
- 38Neoadjuvant Ipilimumab Plus Nivolumab Versus Standard Adjuvant Nivolumab in Macroscopic Stage III Melanoma (NADINA; NCT04949113)
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.