Abstract
The possibilities in treating melanoma patients changed dramatically in the last few years. Several new immunotherapies and targeted therapies have demonstrated promising antitumor activity with manageable side effects in patients with advanced melanoma. These include ipilimumab and PD-1(L) antibodies, and the targeted agents vemurafenib (BRAF-inhibitor), dabrafenib (BRAF-inhibitor), and trametinib (MEK-inhibitor). Although early clinical trials have not indicated that any of these offers a “breakthrough” in terms of antitumor activity for all patients, each will likely offer incremental improvements over standard care. Complex immunotherapies with adoptive T-cell transfer after nonmyeloablative lymphodepletion suggest response rates that are extraordinary; however, these results were derived from highly selected patient cohorts in single centers only. In the adjuvant setting interferon-α is still considered standard of care for high-risk melanoma patients. However, improvement rates for overall survival are still low. Therefore, sufficient markers for selection of patients who will profit from interferon-α are urgently needed. Newdrugs such as ipilimumab and BRAF/MEK inhibitors are already in clinical trials in the adjuvant setting, and may probably improve the possibilities to treat patients being at high risk for recurrence in a few years.
Résumé
Les possibilités de traitement des patients atteints de mélanome( s) ont radicalement changé au cours de ces dernières années. Plusieurs nouvelles immunothérapies et thérapies ciblées ont révélé des résultats prometteurs quant à l’activité tumorale avec des effets secondaires gérables sur les patients atteints d’un mélanome avancé. Celles-ci comprennent les anticorps ipilimumab et PD-1(L) ainsi que les agents ciblés suivants: le vemurafenib (inhibiteur de BRAF), le dabrafenib (inhibiteur de BRAF) et le trametinib (inhibiteur de MEK). Bien que de premiers essais cliniques n’aient pas indiqué que l’un de ces éléments constitue une « révolution » en termes d’activité antitumorale pour tous les patients, chacun d’entre eux apportera des améliorations progressives par rapport aux soins standard. Les immunothérapies complexes avec un transfert adoptif de lymphocytes T suite à une lymphodéplétion non myéloablative indiquent des taux de réponse extraordinaires. Cependant, ces résultats sont issus d’une cohorte de patients sélectionnés avec soin dans des centres uniques. Le traitement adjuvant par interféron-α est toujours considéré comme la norme en matière de soins pour les patients atteints d’un mélanome à haut risque. Néanmoins, les taux d’amélioration de la survie globale sont encore bas. Par conséquent, la nécessité d’obtenir des repères suffisants pour la sélection des patients qui bénéficieront de l’interféron-α s’impose de toute urgence. De nouveaux médicaments tels que l’ipilimumab et les inhibiteurs de BRAF/ MEK sont déjà utilisés pour les essais cliniques du traitement adjuvant et pourraient probablement améliorer les possibilités de traitement de patients à haut risque de récidive dans quelques années.
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Eigentler, T.K., Garbe, C. New landscape in the treatment of melanoma: a 2012 update. Oncologie 15, 71–77 (2013). https://doi.org/10.1007/s10269-013-2258-x
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DOI: https://doi.org/10.1007/s10269-013-2258-x
Mots clés
- Mélanome
- Traitement adjuvant
- Traitement systémique
- Immunothérapies
- Inhibiteurs de BRAF
- Inhibiteurs de MEK