Long-term safety of BLP25 liposome vaccine (L-BLP25) in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC).

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Author(s): C. Butts,
H. Anderson, A. Maksymiuk, D. Vergidis, D. Soulières, Y. Cormier, M.
Davis, E. Marshall, M. Falk, G. Goss; Cross Cancer Institute, Edmonton,
AB, Canada; Vancouver Island Cancer Centre, Victoria, BC, Canada;
Cancer Care Manitoba, Winnipeg, MB, Canada; Northwestern Ontario
Regional Cancer Centre, Thunder Bay , ON, Canada; CHUM, Montreal, QC,
Canada; Université Laval, Quebec, QC, Canada; Nova Scotia Cancer
Centre, Halifax, NS, Canada; Clatterbridge Centre for Oncology,
Bebington, United Kingdom; Merck KGaA, Darmstadt, Germany; The Ottawa
Hospital Cancer Centre, Ottawa, ON, Canada
 
Abstract:
Background:
The BLP25 liposome vaccine (L-BLP25, Stimuvax) is an investigational
innovative therapeutic cancer vaccine incorporating immunoadjuvant
monophosphoryl lipid A and synthetic MUC1 lipopeptide in a liposomal
delivery system. In an open-label phase IIb study in 171 pts with stage
IIIB/IV NSCLC randomized to best supportive care (BSC) alone (n=83) or
BSC + L-BLP25 (1000 µg lipopeptide) (n=88), L-BLP25 pts received weekly
vaccinations for 8 weeks (wks) and could continue maintenance
vaccinations every 6 wks from wk 13. Results were encouraging (Butts et
al, JCO 2005) and a remarkable number of pts received prolonged
treatment (tmt). As a result a global phase III study (START) has been
initiated.
 
Methods: Safety results for 16 pts from the phase IIb study treated for ?2 years with L-BLP25 are reported.
 
Results:
In these 16 pts (median age 57.5 years, ECOG PS: 0 in 5/16 [31%] and 1
in 11/16 [69%]), there were more females (56% vs 44% [9/16 vs 76/171])
and locoregional stage IIIB disease at entry (81% vs 38% [13/16 vs
65/171]) vs the phase IIb study population. Pts received L-BLP25 for
2.0-7.7 years and 10 pts were treated for >5 years. Compliance with
tmt was good: almost all (96%) maintenance vaccinations were given
every 6 wks according to the tmt schedule. L-BLP25 was well tolerated:
the most common tmt-emergent adverse events (TEAEs) were cough (n=12,
75%), fatigue (n=12, 75%), and dyspnea (n=11, 69%). The pattern of
TEAEs did not change significantly over time and there was no rise in
the incidence of TEAEs with increasing time on tmt. Among the most
common TEAEs in years 1, 2, and >2 were nausea (44, 19, and 38%),
fatigue (56, 18, and 38%), chest pain (38, 31, and 31%), and cough (38,
25, and 31%). Twelve pts (75%) had tmt-related TEAEs (grade 1/2 in
11/12 pts [92%] and grade 3 in 1/12 [8%]): the most common were
injection-site reactions. The occurrence of tmt-related TEAEs decreased
with increasing tmt duration. There was no evidence of any TEAEs
related to autoimmunity. Analysis of laboratory data did not indicate
any long-term renal, liver, or other toxicity.
 
Conclusions:
Long-term use of L-BLP25 was without any identifiable safety issues. In
particular, there was no evidence of autoimmune reactions with
prolonged use.