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Recenzirano
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Ascierto, Paolo Antonio; Ferrucci, Pier Francesco; Fisher, Rosalie; Del Vecchio, Michele; Atkinson, Victoria; Schmidt, Henrik; Schachter, Jacob; Queirolo, Paola; Long, Georgina V; Di Giacomo, Anna Maria; Svane, Inge Marie; Lotem, Michal; Bar-Sela, Gil; Couture, Felix; Mookerjee, Bijoyesh; Ghori, Razi; Ibrahim, Nageatte; Moreno, Blanca Homet; Ribas, Antoni
Nature medicine, 06/2019, Letnik: 25, Številka: 6Journal Article
Blocking programmed death 1 (PD-1) may enhance the durability of anti-tumor responses that are induced by the combined inhibition of BRAF and MEK . Here we performed a randomized phase 2 trial ( NCT02130466 ), in which patients with treatment-naive BRAF -mutant, advanced melanoma received the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib together with the PD-1-blocking antibody pembrolizumab (triplet; n = 60) or placebo (doublet; n = 60). The primary end point of progression-free survival was numerically improved in the triplet group-16.0 months-compared with 10.3 months in the doublet group (hazard ratio, 0.66; P = 0.043); however, the trial did not reach the planned benefit for a statistically significant improvement. Median duration of response was 18.7 months (95% confidence interval, 10.1-22.1) and 12.5 months (95% confidence interval, 6.0-14.1); 59.8 and 27.8% of responses were estimated to have lasted for more than 18 months for triplet and doublet treatment, respectively. Grade 3-5 treatment-related adverse events occurred in 58.3 and 26.7% of patients treated with triplet and doublet therapies, respectively, which were most commonly fever, increased transaminase levels and rash. One patient who received triplet therapy died of pneumonitis. In summary, triplet therapy with dabrafenib, trametinib and pembrolizumab conferred numerically longer progression-free survival and duration of response with a higher rate of grade 3/4 adverse events compared with the doublet therapy of dabrafenib, trametinib and placebo.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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