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Metastasised or non-operable melanomas: progress

In patients suffering from a metastasised or inoperable melanoma with or without a genetic mutation, new antitumor drugs are making it possible to prolong life for several months, at the price however of sometimes severe adverse effects.

Melanoma is an aggressive skin cancer which generally appears at around the age of 60, initially treated through surgery. When the cancerous cells disperse and cause secondary cancers (metastases), 50% of patients die within a year.

In around 50% of patients, a mutation of the BRAF protein gene is present in the tumour. Treatment varies according to whether this mutation is present or not.

When there is a mutation of the BRAF protein gene, until now the first-choice treatment has been a BRAF protein inhibitor, vemurafenib in particular, which prolongs life by several months. The combination of trametinib, an antitumour drug from a different pharmacological class, with dabrafenib, another BRAF protein inhibitor, prolongs the survival rate by several months compared with vemurafenib or dabrafenib alone. But trametinib exposes patients to multiple and frequent adverse effects, which can be severe or even fatal. Currently, the combination of trametinib + dabrafenib is the first choice for patients who accept trametinib’s strong toxicity in the hope of gaining several months of life.

In patients suffering from a metastasised or inoperable melanoma without a mutation of the BRAF protein gene, and who have not yet received drug therapy, nivolumab increases the proportion of patients still alive one year later from 40 to 70%, compared with dacarbazine. In 2016, nivolumab is the first-line treatment for this cancer, in spite of its many adverse effects, which can be severe or even fatal.

©Prescrire 1 December 2016

"Trametinib (Mekinist°). Metastatic or inoperable BRAF V600-positive melanoma: a few extra months of life" Prescrire Int 2016; 25 (177): 285-288. (Pdf, subscribers only).

"Nivolumab (Opdivo°). BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage" Prescrire Int 2016; 25 (177): 289-292. (Pdf, subscribers only).
Download the full reviews:

Trametinib (Mekinist°)
Pdf, subscribers only

Nivolumab (Opdivo°)
Pdf, subscribers only

See also:

Cobimetinib (Cotellic°)
and metastatic melanoma
(December 2016)
Free

Ipilimumab and inoperable
or metastatic melanoma.
More evaluation needed, in
both first- and second-line use
Prescrire Int 2015:
25 (159): 96.
Pdf, subscribers only

Dabrafenib. Metastatic melanoma:
a me-too of vemurafenib
Prescrire Int 2015:
25 (159): 90.
Pdf, subscribers only

Vemurafenib with longer follow-up.
Metastatic melanoma: a few
extra months of life, but
many adverse effects
Prescrire Int 2015:
25 (159): 89-90.
Pdf, subscribers only

Ipilimumab in metastatic melanoma:
more assessment is needed
(June 2012)
Free