Treatment
Systemic Therapy Options
Unresectable/Metastatic Cutaneous Melanoma
➤ Recommendation 3.1. For patients with BRAF wild type, unresectable/
metastatic cutaneous melanoma, the following treatment options should
be offered (in no particular order): ipilimumab plus nivolumab followed
by nivolumab OR nivolumab OR pembrolizumab. See Table 2 for
recommended dosing and scheduling details. (Strong recommendation;
EB-B-H)
Qualifying Statements: In the relevant randomized trials, nivolumab could be
continued beyond 2 years while pembrolizumab was limited to 2 years. It is possible
that shorter courses of therapy, as little as one year, may be reasonable. However,
no high-quality data in the melanoma setting addresses what the duration of
therapy should be. For longer dosing cycles (e.g. up to 6 weeks between doses as has
been approved in Europe for pembrolizumab), appropriate monitoring for disease
progression is still necessary.
➤ Recommendation 3.2. For patients with BRAF mutant (V600)
unresectable/metastatic cutaneous melanoma, the following treatment
options should be offered (in no particular order): ipilimumab plus
nivolumab followed by nivolumab OR nivolumab OR pembrolizumab
OR dabrafenib plus trametinib OR encorafenib plus binimetinib OR
vemurafenib plus cobimetinib. See Table 2 for recommended dosing and
scheduling details. (Strong recommendation; EB-B-H)
Qualifying Statements: Switching between BRAF/MEK inhibitor combinations
may be reasonable if patients experience toxicity, as each combination can present
somewhat different toxicity profiles. In the clinical context of BRAF/MEK
inhibitor failure, no data exist regarding the efficacy of switching to a different
BRAF/MEK combination. For longer dosing cycles for anti-PD1 regimens (e.g.
up to 6 weeks between doses as has been approved in Europe for pembrolizumab),
appropriate monitoring for disease progression is still necessary.
➤ Recommendation 3.3. After progression on anti-PD1 therapy patients
with unresectable/metastatic BRAF-wild-type cutaneous melanoma may
be offered ipilimumab or ipilimumab-containing regimens. Talimogene
laherparepvec (T-VEC) therapy may be offered to patients with injectable
lesions. (Weak recommendation; IC)
