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

MMAIT-IV Clinical Trial Group

doi:10.1245/s10434-017-6072-3

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

MMAIT-IV Clinical Trial Group

School of Medicine

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

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 language	English (US)
Pages (from-to)	3991-4000
Number of pages	10
Journal	Annals of surgical oncology
Volume	24
Issue number	13
DOIs	https://doi.org/10.1245/s10434-017-6072-3
State	Published - Dec 1 2017

ASJC Scopus subject areas

Surgery
Oncology

Access to Document

10.1245/s10434-017-6072-3

Cite this

@article{c1aea472e8b2484481e7ff5bea5d6819,

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{\texttrademark}) 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 William Sharfman",

note = "Funding Information: ACKNOWLEDGMENT Supported by grants CA76489 and CA012582 from the National Institutes of Health, National Cancer Institute, and by funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The trial was also funded by CancerVax Corporation, Carlsbad, CA. Funding Information: Supported by grants CA76489 and CA012582 from the National Institutes of Health, National Cancer Institute, and by funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The trial was also funded by CancerVax Corporation, Carlsbad, CA. John F. Thompson, MD (Royal Prince Alfred Hospital, Sydney, Australia); Mark Smithers, MB, BS (Princess Alexandra Hospital, Brisbane, Australia); Michael Hughes, MBBS (Westmead Hospital, Westmead, Australia); Brendon J. Coventry, MB, BS, PhD (Royal Adelaide Hospital, Adelaide, Australia); Jeremy Shapiro, MBBS (Alfred Hospital, Melbourne, Australia); Grant McArthur, MBBS, PhD (Peter MacCallum Cancer Centre, Melbourne, Australia); Antonio Buzaid, MD (Hospital Sirio Libanes, Sao Paulo, Brazil); Wilson Miller, MD (McGill University, Montreal, Quebec, Canada); Dirk Schadendorf, MD (University Hospital of Mannheim, Mannheim, Germany); Claus Garbe, MD (University of Tuebingen, Tuebingen, Germany); Martin Kaatz, MD (University of Jena, Jena, Germany); Ralf Uwe Peter, MD, PhD (University of Ulm, Ulm, Germany); Patrick Terheyden, MD (University Hospital Wuerzburg, Wuerzburg, Germany); Angus Dalgleish, MD (St. George{\textquoteright}s Hospital Medical School, London, Great Britain); Paul Redmond, MD (Cork University Hospital, Cork, Ireland); Schlomo Schneebaum, MD (Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel); Nicola Mozzillo, MD (Istituto Nazionale dei Tumori de Napoli, Naples, Italy); Alessandro Testori, MD (Istituto Europeo Di Oncologia, Milan, Italy); Mario Santinami, MD (Istituto Nazionale dei Tumori-Milano, Milan, Italy); Harald J. Hoekstra, MD, PhD (University Medical Center Groningen and University of Groningen, Groningen, The Netherlands); Michael McCrystal, MD (North Shore Hospital, Auckland, New Zealand); Reinhard Dummer, MD (University of Zurich, Zurich, Switzerland); Mohammed Kashani-Sabet, MD (University of California, San Francisco, Mt. Zion Medical Center, CA, USA); Mark C. Kelley, MD (Vanderbilt University, Nashville, TN, USA); Ronald DeConti, MD (H. Lee Moffitt Cancer Center, Tampa, FL, USA); Jeffrey Lee, MD (MD Anderson Cancer Center, Houston, TX, USA); James F. Huth, MD (University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA); Mark Faries, MD (John Wayne Cancer Institute, Santa Monica, CA, USA); Jeffrey Wagner, TX (Wagner, Wagner & Associates, Indianapolis, IN, USA); Evan Hersh, MD (Arizona Cancer Center, Tucson, AZ, USA); Clay Anderson, MD (University of Missouri, Columbia, MO, USA); Kelly McMasters, MD (University of Louisville, Louisville, KY, USA); Lynn Schuchter, MD (University of Pennsylvania Cancer Center, Philadelphia, PA, USA); Constantine P. Karakousis, MD, PhD (Millard Fillmore Hospital, Buffalo, NY, USA); William Kraybill, MD (Roswell Park Cancer Institute, Buffalo, NY, USA); Rene Gonzalez, MD (University of Colorado Cancer Center, Aurora, CO, USA); David Byrd, MD (University of Washington, Seattle, WA, USA); David Ollila, MD (University of North Carolina-Chapel Hill, Chapel Hill, NC, USA); Michael Walker, MD (Ohio State University, Columbus, OH, USA); Ernest Borden, MD (Cleveland Clinic Foundation, Cleveland, OH, USA); Marie-France Demierre, MD (Boston Medical Center, Boston, USA); Dirk Noyes, MD (IHC Cancer Services-LDS Hospital, Salt Lake City, UT, USA); Douglas Reintgen, MD (Lakeland Regional Cancer Center, Lakeland, FL, USA); Lee Riley, MD (St. Luke{\textquoteright}s Hospital Cancer Center, Bethlehem, PA, USA); Kathy Yao, MD (Loyola University Medical Center, Chicago, IL, USA); Howard Kaufman, MD (Columbia University, New York, NY, USA); Philip Leming, MD (Christ Hospital, Cinncinnati, OH, USA); Edward Levine, MD (Wake Forest University, Winston-Salem, NC, USA); Neal Ready, MD (BrUOG-Rhode Island Hospital, Providence, RI, USA); Gregory Sarna, MD (Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, USA); William Sharfman, MD (Sidney Kimel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA); Robert Dillman, MD (Hoag Cancer Center, Huntington Beach, CA, USA); Norman Estes, MD (OSF Saint Francis Medical Center, Peoria, IL, USA); Laura Hutchins, MD (University of Arkansas for Medical Sciences (UAMS), Little Rock, AK, USA); Andrew Pecora, MD (Hackensack University Medical Center, Hackensack, NJ, USA); John Richart, MD (St. Louis University Health Sciences Center, St. Louis, MO, USA); Neal Rothschild, MD (Palm Beach Cancer Institute, West Palm Beach, FL, USA); John Vetto, MD (Oregon Health Sciences University, Portland, OR, USA); Harold Wanebo, MD (BrUOG-Roger Williams Hospital, Providence, RI, USA); Michael Warso, MD (University of Illinois at Chicago, Chicago, IL, USA); Ned Carp, MD, PhD (Lankenau Hospital, Wynnewood, PA, USA); George Elias, MD (Franklin Square Hospital Center, Baltimore, MD, USA); Mark Greene, MD (Mayo Clinic Scottsdale, AZ, USA); David Hyams, MD (Comprehensive Cancer Center of the Desert, Palm Springs, CA, USA); Jose Lutzky, MD (Mt. Sinai Comprehensive Cancer Center, Miami Beach, FL, USA); Jonathan Polikoff, MD (Kaiser Hospital, Riverside, CA, USA); Armando Sardi, MD (St. Agnes Healthcare, Baltimore, MD, USA); Frank Senecal, MD (Northwest Medical Specialties, Tacoma, WA, USA). Guy Gammon, Daniel Pertschuk and Christopher Nardo were employees of the CancerVax Corporation. Donald L. Morton was a stockholder and patent holder for CancerVax Corporation and Canvaxin, respectively. There are no other relelvant conflicts. Collaborators of the MMAIT-IV Clinical Trial Group are listed in “Acknowledgment”. Publisher Copyright: {\textcopyright} 2017, Society of Surgical Oncology.",

year = "2017",

month = dec,

day = "1",

doi = "10.1245/s10434-017-6072-3",

language = "English (US)",

volume = "24",

pages = "3991--4000",

journal = "Annals of surgical oncology",

issn = "1068-9265",

publisher = "Springer New York",

number = "13",

}

TY - JOUR

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 - Sharfman, William

N1 - Funding Information: ACKNOWLEDGMENT Supported by grants CA76489 and CA012582 from the National Institutes of Health, National Cancer Institute, and by funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The trial was also funded by CancerVax Corporation, Carlsbad, CA. Funding Information: Supported by grants CA76489 and CA012582 from the National Institutes of Health, National Cancer Institute, and by funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The trial was also funded by CancerVax Corporation, Carlsbad, CA. John F. Thompson, MD (Royal Prince Alfred Hospital, Sydney, Australia); Mark Smithers, MB, BS (Princess Alexandra Hospital, Brisbane, Australia); Michael Hughes, MBBS (Westmead Hospital, Westmead, Australia); Brendon J. Coventry, MB, BS, PhD (Royal Adelaide Hospital, Adelaide, Australia); Jeremy Shapiro, MBBS (Alfred Hospital, Melbourne, Australia); Grant McArthur, MBBS, PhD (Peter MacCallum Cancer Centre, Melbourne, Australia); Antonio Buzaid, MD (Hospital Sirio Libanes, Sao Paulo, Brazil); Wilson Miller, MD (McGill University, Montreal, Quebec, Canada); Dirk Schadendorf, MD (University Hospital of Mannheim, Mannheim, Germany); Claus Garbe, MD (University of Tuebingen, Tuebingen, Germany); Martin Kaatz, MD (University of Jena, Jena, Germany); Ralf Uwe Peter, MD, PhD (University of Ulm, Ulm, Germany); Patrick Terheyden, MD (University Hospital Wuerzburg, Wuerzburg, Germany); Angus Dalgleish, MD (St. George’s Hospital Medical School, London, Great Britain); Paul Redmond, MD (Cork University Hospital, Cork, Ireland); Schlomo Schneebaum, MD (Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel); Nicola Mozzillo, MD (Istituto Nazionale dei Tumori de Napoli, Naples, Italy); Alessandro Testori, MD (Istituto Europeo Di Oncologia, Milan, Italy); Mario Santinami, MD (Istituto Nazionale dei Tumori-Milano, Milan, Italy); Harald J. Hoekstra, MD, PhD (University Medical Center Groningen and University of Groningen, Groningen, The Netherlands); Michael McCrystal, MD (North Shore Hospital, Auckland, New Zealand); Reinhard Dummer, MD (University of Zurich, Zurich, Switzerland); Mohammed Kashani-Sabet, MD (University of California, San Francisco, Mt. Zion Medical Center, CA, USA); Mark C. Kelley, MD (Vanderbilt University, Nashville, TN, USA); Ronald DeConti, MD (H. Lee Moffitt Cancer Center, Tampa, FL, USA); Jeffrey Lee, MD (MD Anderson Cancer Center, Houston, TX, USA); James F. Huth, MD (University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA); Mark Faries, MD (John Wayne Cancer Institute, Santa Monica, CA, USA); Jeffrey Wagner, TX (Wagner, Wagner & Associates, Indianapolis, IN, USA); Evan Hersh, MD (Arizona Cancer Center, Tucson, AZ, USA); Clay Anderson, MD (University of Missouri, Columbia, MO, USA); Kelly McMasters, MD (University of Louisville, Louisville, KY, USA); Lynn Schuchter, MD (University of Pennsylvania Cancer Center, Philadelphia, PA, USA); Constantine P. Karakousis, MD, PhD (Millard Fillmore Hospital, Buffalo, NY, USA); William Kraybill, MD (Roswell Park Cancer Institute, Buffalo, NY, USA); Rene Gonzalez, MD (University of Colorado Cancer Center, Aurora, CO, USA); David Byrd, MD (University of Washington, Seattle, WA, USA); David Ollila, MD (University of North Carolina-Chapel Hill, Chapel Hill, NC, USA); Michael Walker, MD (Ohio State University, Columbus, OH, USA); Ernest Borden, MD (Cleveland Clinic Foundation, Cleveland, OH, USA); Marie-France Demierre, MD (Boston Medical Center, Boston, USA); Dirk Noyes, MD (IHC Cancer Services-LDS Hospital, Salt Lake City, UT, USA); Douglas Reintgen, MD (Lakeland Regional Cancer Center, Lakeland, FL, USA); Lee Riley, MD (St. Luke’s Hospital Cancer Center, Bethlehem, PA, USA); Kathy Yao, MD (Loyola University Medical Center, Chicago, IL, USA); Howard Kaufman, MD (Columbia University, New York, NY, USA); Philip Leming, MD (Christ Hospital, Cinncinnati, OH, USA); Edward Levine, MD (Wake Forest University, Winston-Salem, NC, USA); Neal Ready, MD (BrUOG-Rhode Island Hospital, Providence, RI, USA); Gregory Sarna, MD (Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, USA); William Sharfman, MD (Sidney Kimel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA); Robert Dillman, MD (Hoag Cancer Center, Huntington Beach, CA, USA); Norman Estes, MD (OSF Saint Francis Medical Center, Peoria, IL, USA); Laura Hutchins, MD (University of Arkansas for Medical Sciences (UAMS), Little Rock, AK, USA); Andrew Pecora, MD (Hackensack University Medical Center, Hackensack, NJ, USA); John Richart, MD (St. Louis University Health Sciences Center, St. Louis, MO, USA); Neal Rothschild, MD (Palm Beach Cancer Institute, West Palm Beach, FL, USA); John Vetto, MD (Oregon Health Sciences University, Portland, OR, USA); Harold Wanebo, MD (BrUOG-Roger Williams Hospital, Providence, RI, USA); Michael Warso, MD (University of Illinois at Chicago, Chicago, IL, USA); Ned Carp, MD, PhD (Lankenau Hospital, Wynnewood, PA, USA); George Elias, MD (Franklin Square Hospital Center, Baltimore, MD, USA); Mark Greene, MD (Mayo Clinic Scottsdale, AZ, USA); David Hyams, MD (Comprehensive Cancer Center of the Desert, Palm Springs, CA, USA); Jose Lutzky, MD (Mt. Sinai Comprehensive Cancer Center, Miami Beach, FL, USA); Jonathan Polikoff, MD (Kaiser Hospital, Riverside, CA, USA); Armando Sardi, MD (St. Agnes Healthcare, Baltimore, MD, USA); Frank Senecal, MD (Northwest Medical Specialties, Tacoma, WA, USA). Guy Gammon, Daniel Pertschuk and Christopher Nardo were employees of the CancerVax Corporation. Donald L. Morton was a stockholder and patent holder for CancerVax Corporation and Canvaxin, respectively. There are no other relelvant conflicts. Collaborators of the MMAIT-IV Clinical Trial Group are listed in “Acknowledgment”. Publisher Copyright: © 2017, Society of Surgical Oncology.

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.

UR - http://www.scopus.com/inward/record.url?scp=85030836363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030836363&partnerID=8YFLogxK

U2 - 10.1245/s10434-017-6072-3

DO - 10.1245/s10434-017-6072-3

M3 - Article

C2 - 29019177

AN - SCOPUS:85030836363

SN - 1068-9265

VL - 24

SP - 3991

EP - 4000

JO - Annals of surgical oncology

JF - Annals of surgical oncology

IS - 13

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this