Mark B Faries1, Nicola Mozzillo2, Mohammed Kashani-Sabet3, John F Thompson4, Mark C Kelley5, Ronald C DeConti6, Jeffrey E Lee7, James F Huth8, Jeffrey Wagner9, Angus Dalgleish10, Daniel Pertschuk11, Christopher Nardo11, Stacey Stern12, Robert Elashoff13, Guy Gammon11, Donald L Morton12. 1. John Wayne Cancer Institute, Santa Monica, CA, USA. mfaries@theangelesclinic.org. 2. Istituto Nazionale dei Tumori de Napoli, Naples, Italy. 3. Mt. Zion Medical Center, University of California, San Francisco, San Francisco, CA, USA. 4. Royal Prince Alfred Hospital, Sydney, Australia. 5. Vanderbilt University, Nashville, TN, USA. 6. H. Lee Moffitt Cancer Center, Tampa, FL, USA. 7. MD Anderson Cancer Center, Houston, TX, USA. 8. Southwestern Medical Center at Dallas, University of Texas, Dallas, TX, USA. 9. Wagner & Associates, Indianapolis, IN, USA. 10. St. George's Hospital Medical School, London, Great Britain. 11. CancerVax Corp, Carlsbad, CA, USA. 12. John Wayne Cancer Institute, Santa Monica, CA, USA. 13. UCLA Life Sciences, Biomathematics, Los Angeles, CA, USA.
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.
RCT Entities:
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.
Authors: Danielle M Bello; Katherine S Panageas; Travis Hollmann; Alexander N Shoushtari; Parisa Momtaz; Paul B Chapman; Michael A Postow; Margaret K Callahan; Jedd D Wolchok; Mary S Brady; Daniel G Coit; Charlotte E Ariyan Journal: Ann Surg Oncol Date: 2019-12-17 Impact factor: 5.344