Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses.
BACKGROUND
Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START.


METHODS
START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type.


RESULTS
Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77-1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68-0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed.


CONCLUSIONS
Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit.
NCT00409188.
Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Melbourne, Australia. Electronic address: paul.mitchell@austin.org.au.
P
P
Mitchell
Christie Hospital NHS Trust, Manchester, UK.
N
N
Thatcher
UPMC Cancer Pavilion, Pittsburgh, USA.
M A
MA
Socinski
University of Warmia and Mazury, Olsztyn, Poland.
E
E
Wasilewska-Tesluk
Princess Alexandra Hospital, Woolloongabba, Australia.
K
K
Horwood
Mazowieckie Centrum Leczenia Chorób Pluc i Gruzlicy, Otwock, Poland.
A
A
Szczesna
Division of Clinical Oncology, Instituto Especializado Alexander Fleming, Buenos Aires, Argentina.
C
C
Martín
Medical Radiological Research Center, Obninsk, Russia.
Y
Y
Ragulin
Clinical Oncology, Instituto Nacional do Câncer-INCA, Rio de Janeiro, Brazil.
M
M
Zukin
Merck KGaA, Darmstadt, Germany.
C
C
Helwig
Merck KGaA, Darmstadt, Germany.
M
M
Falk
Cancer Care, Cross Cancer Institute, Edmonton.
C
C
Butts
University Health Network, Princess Margaret Cancer Centre, Toronto, Canada.
F A
FA
Shepherd
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood* / Q000276:immunology; D009504:Neutrophils; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000974:Antibodies, Antinuclear; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; C518273:L-BLP25; C060192:MUC1 protein, human; D008562:Membrane Glycoproteins; D018396:Mucin-1
ANA; MUC1; soluble MUC1; tecemotide