Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study.
OBJECTIVE
The TroVax Renal Immunotherapy Survival Trial was a randomized, placebo-controlled phase III study that investigated whether modified vaccinia Ankara encoding the tumor antigen 5T4 (MVA-5T4) prolonged survival of patients receiving first-line standard-of-care (SOC) treatment for metastatic renal cell cancer.


METHODS
Patients with metastatic clear cell renal cancer, prior nephrectomy, and good or intermediate prognosis were randomized 1:1 to receive up to 13 immunizations of MVA-5T4/placebo in combination with either sunitinib, interleukin-2 or interferon-α. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety.


RESULTS
Seven hundred thirty-three patients were recruited (365 MVA-5T4 and 368 placebo). Treatment arms were well balanced for SOC and prognosis. No significant difference in the incidence of adverse events or serious adverse events was observed. No significant difference in overall survival was evident in the two treatment arms (median 20.1 months MVA-5T4 versus 19.2 months placebo; P = 0.55). The magnitude of the 5T4-specific antibody response induced by vaccination with MVA-5T4 was associated with enhanced patient survival. Furthermore, exploratory analyses suggested a number of pretreatment hematologic factors that could identify patients who derive significant benefit from this vaccine.


CONCLUSIONS
MVA-5T4 in combination with SOC was well tolerated, but no difference in survival was observed in the overall study population. Exploratory analyses indicate that there may be subsets of patients who could gain significant benefit from MVA-5T4, but such results would need to be confirmed in future randomized clinical studies.
Amato
Robert J
RJ
The University of Texas/Memorial Hermann Hospital, Houston, TX, USA.
Hawkins
Robert E
RE
Kaufman
Howard L
HL
Thompson
John A
JA
Tomczak
Piotr
P
Szczylik
Cezary
C
McDonald
Mike
M
Eastty
Sarah
S
Shingler
William H
WH
de Belin
Jackie
J
Goonewardena
Madusha
M
Naylor
Stuart
S
Harrop
Richard
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA; D055815:Young Adult
D019496:Cancer Vaccines; D010919:Placebos; C504058:TroVax; D019444:Vaccines, DNA