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

MMAIT-IV Clinical Trial Group

Research output: Contribution to journalArticle

19 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

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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 Hersh, {Evan M} and Kelly McMasters and Lynn Schuchter and Karakousis, {Constantine P.}",
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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 - Hersh, Evan M

AU - McMasters, Kelly

AU - Schuchter, Lynn

AU - Karakousis, Constantine P.

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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