A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer.
BACKGROUND
Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.


METHODS
Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.


RESULTS
This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032).


CONCLUSIONS
Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.
National Cancer Institute, Bethesda, MD, USA. Electronic address: gg496@georgetown.edu.
G
G
Giaccone
Moores Cancer Center, UC San Diego, La Jolla, CA, USA.
L A
LA
Bazhenova
Mary Crowley Cancer Research Centers, Dallas, TX, USA.
J
J
Nemunaitis
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
M
M
Tan
Korányi National Institute for TB and Pulmonology, Budapest, Hungary.
E
E
Juhász
Wielkopolskie Centrum Pulmonologii i Torakochirurgii, Poznań University of Medical Sciences, Poznan, Poland.
R
R
Ramlau
Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Thoracic Oncology, Amsterdam, Netherlands.
M M
MM
van den Heuvel
Guy's Hospital, King's Health Partners, London, England, United Kingdom.
R
R
Lal
James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
G H
GH
Kloecker
Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
K D
KD
Eaton
Cross Cancer Institute, Edmonton, Alberta, Canada.
Q
Q
Chu
Royal Infirmary, Glasgow, Scotland, United Kingdom.
D J
DJ
Dunlop
Noble Hospital, Pune, India.
M
M
Jain
University of California, Los Angeles, Los Angeles, CA, USA.
E B
EB
Garon
CSD Biostatistics, Tucson, AZ, USA.
C S
CS
Davis
NovaRx Corporation, San Diego, CA, USA.
E
E
Carrier
NovaRx Corporation, San Diego, CA, USA.
S C
SC
Moses
NovaRx Corporation, San Diego, CA, USA.
D L
DL
Shawler
NovaRx Corporation, San Diego, CA, USA.
H
H
Fakhrai
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome
D019496:Cancer Vaccines; C514428:belagenpumatucel L
Cancer gene therapy; Cancer immunotherapy; Cancer vaccine; Non-small cell lung cancer; TGF-β