A Randomized Phase II Study of Anti-CSF1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple-Negative Breast Cancer
Por:
Kuemmel, S, Campone, M, Loirat, D, Lopez, RL, Beck, JT, De Laurentiis, M, Im, SA, Kim, SB, Kwong, A, Steger, GG, Adelantado, EZ, Duhoux, FP, Greil, R, Kuter, I, Lu, YS, Tibau, A, Ozguroglu, M, Scholz, CW, Singer, CF, Vega, E, Wimberger, P, Zamagni, C, Couillebault, XM, Fan, LQ, Guerreiro, N, Mataraza, J, Sand-Dejmek, J, Chan, A
Publicada:
1 ene 2022
Resumen:
Purpose: This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC).
Patients and Methods: Female patients with advanced TNBC, with high levels of tumor-associated macrophages not amenable to curative treatment by surgery or radiotherapy were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks, +/- a dose on cycle 1, day 8. Gemcitabine (1,000 mg/m(2)) and carboplatin (dose in mg calculated by area under the curve [mg/mL/min] x (glomerular filtration rate [mL/min] + 25 [mL/min]) were dosed every 3 weeks. Treatment continued until unacceptable toxicity, disease progression, or discontinuation by physician/patient.
Results: Patients received lacnotuzumab + gem-carbo (n = 34) or gem-carbo (n = 15). Enrollment was halted due to recruitment challenges owing to rapid evolution of the therapeutic landscape; formal hypothesis testing of the primary endpoint was therefore not performed. Median progression-free survival was 5.6 months [90% confidence interval (CI), 4.47-8.64] in the lacnotuzumab + gemcarbo arm and 5.5 months [90% CI, 3.45-7.46] in the gem-carbo arm. Hematologic adverse events were common in both treatment arms; however, patients treated with lacnotuzumab experienced more frequent aspartate aminotransferase, alanine aminotransferase, and creatine kinase elevations. Pharmacokinetic results showed that free lacnotuzumab at 10 mg/kg exhibited a typical IgG pharmacokinetic profile and target engagement of circulating colony-stimulating factor 1 ligand.
Conclusions: Despite successful target engagement and anticipated pharmacoldnetic profile, lacnotuzumab + gem-carbo showed comparable antitumor activity to gem-carho alone, with slightly poorer tolerability. However, the data presented in this article would be informative for future studies testing agents targeting the CSFI-CSFI receptor pathway in TNBC.
Filiaciones:
Kuemmel, S:
Kliniken Essen Mitte, Interdisciplinary Breast Unit, D-45136 Essen, Germany
Campone, M:
Ctr Ren Gauducheau, Inst Canc Rol Ouest, St Herblain, France
Loirat, D:
Inst Curie, Med Oncol Dept, Paris, France
Inst Curie, D3i, Paris, France
Lopez, RL:
Clin Univ Hosp, Santiago De Compostela, Spain
Hlth Res Inst Santiago Compostela CIBERONC, Santiago De Compostela, Spain
Beck, JT:
Highlands Oncol Grp, Fayetteville, MA USA
De Laurentiis, M:
Ist Nazl Tumori IRCCS Fdn Pascale, Naples, Italy
Im, SA:
Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Canc Res Inst, Seoul, South Korea
Kim, SB:
Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea
Kwong, A:
Univ Hong Kong, Queen Mary Hosp, Hong Kong, Peoples R China
Steger, GG:
Med Univ Vienna, Dept Internal Med 1, Div Oncol, Vienna, Austria
Med Univ Vienna, Gaston H Glock Res Ctr, Vienna, Austria
Adelantado, EZ:
Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain
Duhoux, FP:
UCLouvain, King Albert II Canc Inst, Clin Univ St Luc, Brussels, Belgium
Greil, R:
Paracelsus Med Univ, Salzburg Canc Res Inst CCCIT, Salzburg, Austria
Paracelsus Med Univ, Canc Cluster Salzburg, Salzburg, Austria
Kuter, I:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA
Lu, YS:
Natl Taiwan Univ Hosp, Taipei, Taiwan
Tibau, A:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Oncol Dept, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Ozguroglu, M:
Istanbul Univ Cerrahpasa, Cerrahpasa Sch Med, Istanbul, Turkey
Scholz, CW:
Vivantes Klinikum Urban, Berlin, Germany
Singer, CF:
Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria
Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria
Vega, E:
CIOCC Grp Hosp Madrid, Madrid, Spain
Wimberger, P:
Tech Univ Dresden, Carl Gustav Carus Univ, Dresden, Germany
Zamagni, C:
Ospdi Bologna, Bologna, Italy
Couillebault, XM:
Novartis Pharma AG, Basel, Switzerland
Fan, LQ:
Novartis Inst BioMed Res, Cambridge, MA USA
Guerreiro, N:
Novartis Pharma AG, Basel, Switzerland
Mataraza, J:
Novartis Inst BioMed Res, Cambridge, MA USA
Sand-Dejmek, J:
Novartis Pharma AG, Basel, Switzerland
Chan, A:
Breast Canc Res Ctr WA, Perth, WA, Australia
Curtin Univ, Perth, WA, Australia
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