ALGORITMI DI TRATTAMENTO NELL’IMMUNOTERAPIA DEL MELANOMA
M Maio e R Danielli
terapeutica sia nei soggetti BRAF mutati che non. Inoltre, l’imminente disponibilità di anticorpi antiPD1 contribuirà indubbiamente a modificare ulteriormente l’attuale algoritmo terapeutico del mela-
noma metastatico. Infine, ulteriori aggiustamenti nella sequenza/somministrazione concomitante di agenti innovativi potrà derivare dai risultati degli studi traslazionali in corso.
BIBLIOGRAFIA 1. Hodi FS, O’Day SJ, McDermott DF et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723. 2. Ascierto PA, Chiarion Sileni V, Del Vecchio M et al: The European ipilimumab expanded access programme (EAP): efficacy and safety data from the Italian cohort of patients with pretreated, advanced melanoma. ESMO annual meeting 2012: 1128P. 3. Queirolo P, Simeone E, et al. Efficacy and safety data from patients with advanced melanoma and brain metastases participating in the European ipilimumab expanded access programme (EAP) in Italy. ESMO annual meeting 2012. 4. Margolin K, Ernstoff MS, Hamid O et al: Ipilimumab in patients with melanoma and brain metastases: an openlabel, phase 2 trial. Lancet Oncol 2012; 13: 459-465. 5. Di Giacomo AM, Ascierto PA, Hamid O et al: Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol 2012; 13: 879-886. 6. Di Giacomo AM, Ascierto P, Fonsatti E et al: Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. SMR annual meeting 2014. 7. Shahabi V, Whitney G, Hamid O et al: Assessment of association between BRAF-V600E mutation status in melanomas and clinical response to ipilimumab. Cancer Immunol Immunother 2012; 61: 733-737. 8. Maio M, Bondarenko I, et al. Four-year survival update for metastatic melanoma (MM) patients (PTS) treated with ipilimumab (IPI) + dacarbazine (DTIC) on phase 3 study CA184-024. JCO: in press. 9. Robert C, Ribas A, Wolchok JD et al: Anti-programmeddeath-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet Oncol 2014; 384: 1109-1117. 10. Weber JS, Minor DR, D’Angelo S et al: A phase 3 randomized, open-label study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus investigator’s choice chemotherapy (ICC) in patients with advanced melanoma after prior anti-CTLA-4 therapy. Esmo annual meeting 2014: LBA3_PR. 11. Robert C, Long GV, Brady B et al: Nivolumab in previously untreated melanoma without BRAF mutation. N Eng J Med 2014; epub ahead of print. 12. Sznol M, Kluger MH, Callahan MS et al: Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). ASCO annual meeting 2014: LBA9003.
13. Chapman PB, Hauschild A, Robert C et al: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516. 14. Dummer R, Goldinger SM, Turtschi CP et al: Vemurafenib in patients with BRAFv600 mutation-positive melanoma with symptomatic brain metastases. Final results of an open-label pilot study. Eur J Cancer 2014; 50: 611-621. 15. Hauschild A, Grob JJ, Demidov LV et al: Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma [abstract]. J Clin Oncol 2012; 30 (Suppl 18): LBA8500. 16. Long GV, Trefzer U, Davies MA et al: Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 1087-1095. 17. Flaherty KT, Robert C, Hersey P et al: Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012; 367: 107-111. 18. Larkin J, Ascierto PA, Dréno B et al: Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371: 1867-1876. 19. Long GV, Stroyakovskiy D, Gogas H et al: Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371: 1877-1888. 20. Ackerman A, McDermott DF, Donald PL et al: Outcome of patients with malignant melanoma treated with immunotherapy prior to after vemurafenib. J Clin Oncol 2012; 30 (suppl): abstr 8569. 21. Ascierto PA, Simeone E, Giannarelli D et al: Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med 2012; 10: 107. 22. Ascierto PA, Simeone E, Sileni VC et al: Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: data from the Italian cohort of the ipilimumab expanded access program. Cancer Invest 2014; 32: 144-149. 23. Flaherty KT, Puzanov I, Kevin B et al: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363: 809-819. 24. Schadendorf D, Hodi FS, Robert C et al: Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in metastatic or locally advanced, unresectable melanoma. Eur J Cancer 2013; 49 (suppl; abstr 24LBA). 25. Jang S, Atkins MB: Which drug, and when, for patients with BRAF-muatnt melanoma? Lancet Oncol 2013; 14: 61-69.
7