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Acral melanoma: the decisions you may face

4 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Dermoscopy of the parallel ridge pattern and biopsy of any changing pigmented lesion of the palm, sole or nail; nail matrix biopsy for longitudinal melanonychia with Hutchinson sign.

The options, in plain words

Magnified skin imaging and whole-body photo mapping, increasingly read by algorithms, to find melanoma early and avoid unnecessary biopsies.

  • Cheap, non-invasive, repeatable
  • Reduces benign excisions when used well

Checking the whole skin for suspicious moles finds melanomas earlier, but no trial has yet shown that screening everyone saves lives, so most countries target people at high risk.

  • Cheap and non-invasive
  • Melanoma is highly curable when thin
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Algorithm performance drops on darker skin and rare subtypes
  • No proven mortality benefit for population screening
  • No randomised trial of mortality benefit
  • Rising melanoma incidence without matching mortality change points to overdiagnosis
  • Performance varies by skin tone and training
Questions to ask about this decision
  1. Between Dermoscopy, total-body photography & AI skin analysis and Skin cancer screening (visual skin examination), which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (diagnosis), which of the standard options do you recommend and why?
    Why: Guideline options include: Dermoscopy of the parallel ridge pattern and biopsy of any changing pigmented lesion of the palm, sole or nail; nail matrix biopsy for longitudinal melanonychia with Hutchinson sign.

Add these to your appointment list, or take the full question set for this cancer.

Early / localised

Localised disease

One path named

Wide local excision with thickness-based margins, distal amputation for subungual disease when needed, sentinel lymph node biopsy for primaries over 0.8 mm.

The path, in plain words

Removing just the first lymph node a tumour drains to, instead of all of them, to check for spread.

  • Avoids lymphoedema from full dissection
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • False negatives in ~5-10%
Questions to ask about this decision
  1. Is Sentinel lymph node biopsy the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (localised disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Wide local excision with thickness-based margins, distal amputation for subungual disease when needed, sentinel lymph node biopsy for primaries over 0.8 mm.

Add these to your appointment list, or take the full question set for this cancer.

Locally advanced

Resected stage III

Adjuvant nivolumab or pembrolizumab; dabrafenib-trametinib for BRAF V600-mutant disease; neoadjuvant immunotherapy for macroscopic nodes as in NADINA.

The options, in plain words

Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.

Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.

Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.

The evidence behind it
  • Tests Nivolumab
    Resectable macroscopic stage III melanoma: two cycles neoadjuvant ipilimumab + nivolumab then surgery (adjuvant only if incomplete response) vs surgery then 12 cycles adjuvant nivolumab

    12-month EFS 83.7% vs 57.2%; HR 0.32.

    Event-free survival at 12 months (%): Neoadjuvant ipilimumab + nivolumab 83.7 vs Adjuvant nivolumab 57.2 · HR 0.32 · source
The main trade-offs on record
Side effectAny gradeGrade 3+
Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated25%14.4%
Hepatitis with ipilimumab · Monotherapy pooled unless stated15%13.4%
Colitis · Monotherapy pooled unless stated2.9%1.7%
Hepatitis · Monotherapy pooled unless stated1.8%1.5%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Questions to ask about this decision
  1. Between Nivolumab, Pembrolizumab and Dabrafenib + trametinib, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in NADINA, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Nivolumab or Pembrolizumab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  7. For my situation (resected stage iii), which of the standard options do you recommend and why?
    Why: Guideline options include: Adjuvant nivolumab or pembrolizumab; dabrafenib-trametinib for BRAF V600-mutant disease; neoadjuvant immunotherapy for macroscopic nodes as in NADINA.
  8. Am I a candidate for Nivolumab, Pembrolizumab, Dabrafenib + trametinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  9. How do the results of NADINA apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Nivolumab plus ipilimumab or anti-PD-1 monotherapy; BRAF-MEK inhibitors for BRAF-mutant tumours; imatinib for KIT-mutant tumours; tunlametinib for NRAS-mutant disease in China; trials of CDK4/6 inhibitors.

The options, in plain words

Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.

Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.

Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.

Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.

The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.

Tunlametinib is a Chinese MEK inhibitor approved in 2024 for advanced melanoma with an NRAS mutation, a group with no targeted therapy elsewhere in the world, and in phase 3 trials with vemurafenib for BRAF-mutant disease and for colorectal cancer.

Palbociclib was the first CDK4/6 inhibitor (2015), and in 2026 became the first approved as maintenance in HER2-positive, hormone-positive breast cancer.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
Side effectAny gradeGrade 3+
Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated25%14.4%
Hepatitis with ipilimumab · Monotherapy pooled unless stated15%13.4%
Colitis · Monotherapy pooled unless stated2.9%1.7%
Hepatitis · Monotherapy pooled unless stated1.8%1.5%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma25%14.4%
Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma15%13.4%
Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma28%4.8%
Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma8%2.6%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
  • Take with a meal and a large glass of water.
Side effectAny gradeGrade 3+
Neutropenia · PALOMA-2 with letrozole80%66%
Leukopenia · PALOMA-2 with letrozole39%25%
Infections · PALOMA-2 with letrozole60%7%
Anaemia · PALOMA-2 with letrozole24%6%
  • Capsules: take with food (PPIs lower capsule exposure when fasting). Tablets: with or without food. Avoid grapefruit.
  • Reduce to 75 mg daily in severe impairment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between Nivolumab, Ipilimumab, Pembrolizumab and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. Which side effects of Nivolumab or Ipilimumab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Melanoma: Cutaneous), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (advanced disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab plus ipilimumab or anti-PD-1 monotherapy; BRAF-MEK inhibitors for BRAF-mutant tumours; imatinib for KIT-mutant tumours; tunlametinib for NRAS-mutant disease in China; trials of CDK4/6 inhibitors.
  7. Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.