Treatment of Unresectable Stage III/IV BRAF Wild-Type Cutaneous Melanoma When Immunotherapy Is Unavailable

This protocol covers patients with unresectable stage III or stage IV (metastatic) cutaneous amelanocytic melanoma whose tumour is confirmed BRAF wild-type and for whom clinical trials or immunotherapy cannot be delivered.

Clinical Scenario

Disease is unresectable stage III or stage IV metastatic cutaneous melanoma with confirmed absence of a BRAF V600 mutation. PD-1 blockade is a standard-of-care option in the first-line setting regardless of BRAF status; however, approved options for BRAF wild-type disease beyond the first line are very limited — making this scenario particularly challenging when immunotherapy is not accessible.

Treatment Approach (partial overview)

When clinical trials and immunotherapy are not available, later-line chemotherapy may be considered, with modest activity reported. Rechallenge with a drug class not used in the immediately preceding treatment line may also be discussed in eligible patients.

Full regimen details, drug selection, sequencing, and eligibility criteria are available in the complete protocol →

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.annonc.2024.11.006

Based on these trials, PD-1 blockade is now an SoC option for all patients, regardless of tumour BRAF status, in the first-line setting.

For BRAF-WT melanoma, approved second-line options are very limited.

If clinical trials, ICIs or BRAFis/MEKis are not available, ChT may be administered as later-line therapy [IV, C], with modest activity and no impact on OS.

Third-line treatment rechallenge with the drug class not used in the immediate previous line can be considered, if feasible.

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