Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases

MMAIT-IV Clinical Trial Group

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Background: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. Methods: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). Results: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. Discussion: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

    Original languageEnglish (US)
    Pages (from-to)3991-4000
    Number of pages10
    JournalAnnals of Surgical Oncology
    Volume24
    Issue number13
    DOIs
    StatePublished - Dec 1 2017

    Fingerprint

    Mycobacterium bovis
    Immunotherapy
    Melanoma
    Neoplasm Metastasis
    Survival
    Disease-Free Survival
    Clinical Trials Data Monitoring Committees
    Placebos
    Metastasectomy
    Skin Tests
    Vaccines
    Survival Rate

    ASJC Scopus subject areas

    • Surgery
    • Oncology

    Cite this

    Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases. / MMAIT-IV Clinical Trial Group.

    In: Annals of Surgical Oncology, Vol. 24, No. 13, 01.12.2017, p. 3991-4000.

    Research output: Contribution to journalArticle

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    title = "Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases",
    abstract = "Background: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. Methods: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). Results: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9{\%}, respectively, for BCG/Pl versus 31.4 months and 39.6{\%} in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3{\%}, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4{\%}, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7{\%}, respectively, for BCG/Pl versus 8.5 months, 30.0{\%}, and 30.0{\%}, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. Discussion: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.",
    author = "{MMAIT-IV Clinical Trial Group} and Faries, {Mark B.} and Nicola Mozzillo and Mohammed Kashani-Sabet and Thompson, {John F.} and Kelley, {Mark C.} and DeConti, {Ronald C.} and Lee, {Jeffrey E.} and Huth, {James F.} and Jeffrey Wagner and Angus Dalgleish and Daniel Pertschuk and Christopher Nardo and Stacey Stern and Robert Elashoff and Guy Gammon and Morton, {Donald L.} and Thompson, {John F.} and Mark Smithers and Michael Hughes and Coventry, {Brendon J.} and Jeremy Shapiro and Grant McArthur and Antonio Buzaid and Wilson Miller and Dirk Schadendorf and Claus Garbe and Martin Kaatz and Peter, {Ralf Uwe} and Patrick Terheyden and Angus Dalgleish and Paul Redmond and Schlomo Schneebaum and Nicola Mozzillo and Alessandro Testori and Mario Santinami and Hoekstra, {Harald J.} and Michael McCrystal and Reinhard Dummer and Mohammed Kashani-Sabet and Kelley, {Mark C.} and Ronald DeConti and Jeffrey Lee and Huth, {James F.} and Mark Faries and Jeffrey Wagner and Evan Hersh and Clay Anderson and Kelly McMasters and Lynn Schuchter and John Vetto",
    year = "2017",
    month = "12",
    day = "1",
    doi = "10.1245/s10434-017-6072-3",
    language = "English (US)",
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    journal = "Annals of Surgical Oncology",
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    T1 - Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases

    AU - MMAIT-IV Clinical Trial Group

    AU - Faries, Mark B.

    AU - Mozzillo, Nicola

    AU - Kashani-Sabet, Mohammed

    AU - Thompson, John F.

    AU - Kelley, Mark C.

    AU - DeConti, Ronald C.

    AU - Lee, Jeffrey E.

    AU - Huth, James F.

    AU - Wagner, Jeffrey

    AU - Dalgleish, Angus

    AU - Pertschuk, Daniel

    AU - Nardo, Christopher

    AU - Stern, Stacey

    AU - Elashoff, Robert

    AU - Gammon, Guy

    AU - Morton, Donald L.

    AU - Thompson, John F.

    AU - Smithers, Mark

    AU - Hughes, Michael

    AU - Coventry, Brendon J.

    AU - Shapiro, Jeremy

    AU - McArthur, Grant

    AU - Buzaid, Antonio

    AU - Miller, Wilson

    AU - Schadendorf, Dirk

    AU - Garbe, Claus

    AU - Kaatz, Martin

    AU - Peter, Ralf Uwe

    AU - Terheyden, Patrick

    AU - Dalgleish, Angus

    AU - Redmond, Paul

    AU - Schneebaum, Schlomo

    AU - Mozzillo, Nicola

    AU - Testori, Alessandro

    AU - Santinami, Mario

    AU - Hoekstra, Harald J.

    AU - McCrystal, Michael

    AU - Dummer, Reinhard

    AU - Kashani-Sabet, Mohammed

    AU - Kelley, Mark C.

    AU - DeConti, Ronald

    AU - Lee, Jeffrey

    AU - Huth, James F.

    AU - Faries, Mark

    AU - Wagner, Jeffrey

    AU - Hersh, Evan

    AU - Anderson, Clay

    AU - McMasters, Kelly

    AU - Schuchter, Lynn

    AU - Vetto, John

    PY - 2017/12/1

    Y1 - 2017/12/1

    N2 - Background: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. Methods: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). Results: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. Discussion: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

    AB - Background: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. Methods: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). Results: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. Discussion: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

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