Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group.
OBJECTIVE
Patients with clinically negative nodes constitute over 85% of new melanoma cases. There is no adjuvant therapy for intermediate-thickness, node-negative melanoma patients.


METHODS
The Southwest Oncology Group conducted a randomized phase III trial of an allogeneic melanoma vaccine for 2 years versus observation in patients with intermediate-thickness (1.5 to 4.0 mm or Clark's level IV if thickness unknown), clinically or pathologically node-negative melanoma (T3N0M0).


RESULTS
Six hundred eighty-nine patients were accrued over 4.5 years; 89 patients (13%) were ineligible. Surgical node staging was performed in 24%, the remainder were clinical N0. Thirteen eligible patients refused assigned treatment: seven on the observation arm and six on the vaccine arm. Most vaccine patients experienced mild to moderate local toxicity, but 26 (9%) experienced grade 3 toxicity. After a median follow-up of 5.6 years, there were 107 events (tumor recurrences or deaths) among the 300 eligible patients randomized to vaccine compared with 114 among the 300 eligible patients randomized to observation (hazard ratio, 0.92; Cox-adjusted P(2) = 0.51). There was no difference in vaccine efficacy among patients with tumors < or = 3 mm or > 3 mm.


CONCLUSIONS
This represents one of the largest randomized, controlled trials of adjuvant vaccine therapy in human cancer reported to date. Compliance with randomization was excellent, with only 2% refusing assigned therapy. There is no evidence of improved disease-free survival among patients randomized to receive vaccine, although the power to detect a small but clinically significant difference was low. Future investigations of adjuvant vaccine approaches for patients with intermediate-thickness melanoma should involve larger numbers of patients and ideally should include sentinel node biopsy staging.
Sondak
Vernon K
VK
University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
Liu
P-Y
PY
Tuthill
Ralph J
RJ
Kempf
Raymond A
RA
Unger
Joseph M
JM
Sosman
Jeffrey A
JA
Thompson
John A
JA
Weiss
Geoffrey R
GR
Redman
Bruce G
BG
Jakowatz
James G
JG
Noyes
R Dirk
RD
Flaherty
Lawrence E
LE
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D016016:Proportional Hazards Models
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C116434:Melacine