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Article: A randomized phase II study of anti-CSF1 monoclonal antibody lacnotuzumab (MCS110) combined with gemcitabine and carboplatin in advanced triple-negative breast cancer

TitleA randomized phase II study of anti-CSF1 monoclonal antibody lacnotuzumab (MCS110) combined with gemcitabine and carboplatin in advanced triple-negative breast cancer
Authors
Issue Date2022
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2022, v. 28 n. 1, p. 106-115 How to Cite?
AbstractPurpose: 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/m2) and carboplatin (dose in mg calculated by area under the curve [mg/mL/min] × (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 + gem-carbo 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 pharmacokinetic profile, lacnotuzumab + gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this article would be informative for future studies testing agents targeting the CSF1–CSF1 receptor pathway in TNBC.
Persistent Identifierhttp://hdl.handle.net/10722/310079
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKuemmel, S-
dc.contributor.authorCampone, M-
dc.contributor.authorLoirat, D-
dc.contributor.authorLopez, RL-
dc.contributor.authorBeck, JT-
dc.contributor.authorDe Laurentiis, M-
dc.contributor.authorIm, SA-
dc.contributor.authorKim, SB-
dc.contributor.authorKwong, A-
dc.contributor.authorSteger, GG-
dc.contributor.authorAdelantado, EZ-
dc.contributor.authorDuhoux, FP-
dc.contributor.authorGreil, R-
dc.contributor.authorKuter, I-
dc.contributor.authorLu, YS-
dc.contributor.authorTibau, A-
dc.contributor.authorÖzgüroğlu, M-
dc.contributor.authorScholz, CW-
dc.contributor.authorSinger, CF-
dc.contributor.authorVega, E-
dc.contributor.authorWimberger, P-
dc.contributor.authorZamagni, C-
dc.contributor.authorCouillebault, XM-
dc.contributor.authorFan, L-
dc.contributor.authorGuerreiro, N-
dc.contributor.authorMataraza, J-
dc.contributor.authorSand-Dejmek, J-
dc.contributor.authorChan, A-
dc.date.accessioned2022-01-24T02:23:31Z-
dc.date.available2022-01-24T02:23:31Z-
dc.date.issued2022-
dc.identifier.citationClinical Cancer Research, 2022, v. 28 n. 1, p. 106-115-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/310079-
dc.description.abstractPurpose: 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/m2) and carboplatin (dose in mg calculated by area under the curve [mg/mL/min] × (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 + gem-carbo 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 pharmacokinetic profile, lacnotuzumab + gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this article would be informative for future studies testing agents targeting the CSF1–CSF1 receptor pathway in TNBC.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.titleA randomized phase II study of anti-CSF1 monoclonal antibody lacnotuzumab (MCS110) combined with gemcitabine and carboplatin in advanced triple-negative breast cancer-
dc.typeArticle-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityKwong, A=rp01734-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-20-3955-
dc.identifier.pmid34615719-
dc.identifier.scopuseid_2-s2.0-85123388323-
dc.identifier.hkuros331542-
dc.identifier.volume28-
dc.identifier.issue1-
dc.identifier.spage106-
dc.identifier.epage115-
dc.identifier.isiWOS:000752558900001-
dc.publisher.placeUnited States-

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