TY - JOUR
T1 - Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer
AU - Chick, R. Connor
AU - Clifton, G. Travis
AU - Hale, Diane F.
AU - Vreeland, Timothy J.
AU - Hickerson, Annelies T.
AU - Kemp Bohan, Phillip M.
AU - McCarthy, Patrick M.
AU - Litton, Jennifer K.
AU - Alatrash, Gheath
AU - Murthy, Rashmi K.
AU - Qiao, Na
AU - Philips, Anne
AU - Lukas, Jason
AU - Holmes, Jarrod P.
AU - Mittendorf, Elizabeth A.
AU - Peoples, George E.
N1 - Publisher Copyright:
© 2021
PY - 2021/4
Y1 - 2021/4
N2 - HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.
AB - HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.
KW - Breast cancer
KW - Cancer vaccine
KW - Immunotherapy
KW - Personalized medicine
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U2 - 10.1016/j.clim.2021.108679
DO - 10.1016/j.clim.2021.108679
M3 - Article
C2 - 33485895
AN - SCOPUS:85099982116
SN - 1521-6616
VL - 225
JO - Clinical Immunology
JF - Clinical Immunology
M1 - 108679
ER -