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MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F18%3A10377117" target="_blank" >RIV/00064165:_____/18:10377117 - isvavai.cz</a>

  • Výsledek na webu

    <a href="https://doi.org/10.1016/S1470-2045(18)30254-7" target="_blank" >https://doi.org/10.1016/S1470-2045(18)30254-7</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/S1470-2045(18)30254-7" target="_blank" >10.1016/S1470-2045(18)30254-7</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial

  • Popis výsledku v původním jazyce

    Background: Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting. Methods: DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0.5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445. Findings: Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28.0 months [IQR 23.3-35.5] in the MAGE-A3 group and 28.1 months [23.7-36.9] in the placebo group. Median disease-free survival was 11.0 months (95% CI 10.0-11.9) in the MAGE-A3 group and 11.2 months (8.6-14.1) in the placebo group (hazard ratio [HR] 1.01, 0.88-1.17, p=0.86). In the GS-positive population, median disease-free survival was 9.9 months (95% CI 5.7-17.6) in the MAGE-A3 group and 11.6 months (5.6-22.3) in the placebo group (HR 1.11, 0.83-1.49, p=0.48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [&lt;1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment. Interpretation: An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.

  • Název v anglickém jazyce

    MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial

  • Popis výsledku anglicky

    Background: Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting. Methods: DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0.5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445. Findings: Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28.0 months [IQR 23.3-35.5] in the MAGE-A3 group and 28.1 months [23.7-36.9] in the placebo group. Median disease-free survival was 11.0 months (95% CI 10.0-11.9) in the MAGE-A3 group and 11.2 months (8.6-14.1) in the placebo group (hazard ratio [HR] 1.01, 0.88-1.17, p=0.86). In the GS-positive population, median disease-free survival was 9.9 months (95% CI 5.7-17.6) in the MAGE-A3 group and 11.6 months (5.6-22.3) in the placebo group (HR 1.11, 0.83-1.49, p=0.48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [&lt;1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment. Interpretation: An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30216 - Dermatology and venereal diseases

Návaznosti výsledku

  • Projekt

  • Návaznosti

    N - Vyzkumna aktivita podporovana z neverejnych zdroju

Ostatní

  • Rok uplatnění

    2018

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    The Lancet: Oncology

  • ISSN

    1470-2045

  • e-ISSN

  • Svazek periodika

    19

  • Číslo periodika v rámci svazku

    7

  • Stát vydavatele periodika

    GB - Spojené království Velké Británie a Severního Irska

  • Počet stran výsledku

    14

  • Strana od-do

    916-929

  • Kód UT WoS článku

    000437342400051

  • EID výsledku v databázi Scopus

    2-s2.0-85048352038