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Article: Lucitanib for the treatment of HRþ/HER2- Metastatic breast cancer: Results from the multicohort phase II FINESSE study

TitleLucitanib for the treatment of HR<sup>þ</sup>/HER2<sup>-</sup> Metastatic breast cancer: Results from the multicohort phase II FINESSE study
Authors
Issue Date2020
Citation
Clinical Cancer Research, 2020, v. 26, n. 2, p. 354-363 How to Cite?
AbstractPurpose: The FGFR1 gene is amplified in 14% of patients with HRþ/HER2- breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRa/b, were assessed. Patients and Methods: Patients with HRþ/HER2- metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFR1 nonamplified, 11q13 amplified, and (iii) FGFR1 and 11q13 nonamplified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 amplification (≥4 CNV) than those without high amplification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HRþ/ HER2- MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.
Persistent Identifierhttp://hdl.handle.net/10722/326492
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHui, Rina-
dc.contributor.authorPearson, Alex-
dc.contributor.authorCortes, Javier-
dc.contributor.authorCampbell, Christine-
dc.contributor.authorPoirot, Camille-
dc.contributor.authorAzim, Hatem A.-
dc.contributor.authorFumagalli, Debora-
dc.contributor.authorLambertini, Matteo-
dc.contributor.authorDaly, Fergus-
dc.contributor.authorArahmani, Amal-
dc.contributor.authorPerez-Garcia, José-
dc.contributor.authorAftimos, Philippe-
dc.contributor.authorBedard, Philippe L.-
dc.contributor.authorXuereb, Laura-
dc.contributor.authorScheepers, Elsemieke D.-
dc.contributor.authorVicente, Malou-
dc.contributor.authorGoulioti, Theodora-
dc.contributor.authorLoibl, Sibylle-
dc.contributor.authorLoi, Sherene-
dc.contributor.authorPierrat, Marie Jeanne-
dc.contributor.authorTurner, Nicholas C.-
dc.contributor.authorAndre, Fabrice-
dc.contributor.authorCurigliano, Giuseppe-
dc.date.accessioned2023-03-10T02:19:40Z-
dc.date.available2023-03-10T02:19:40Z-
dc.date.issued2020-
dc.identifier.citationClinical Cancer Research, 2020, v. 26, n. 2, p. 354-363-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/326492-
dc.description.abstractPurpose: The FGFR1 gene is amplified in 14% of patients with HRþ/HER2- breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRa/b, were assessed. Patients and Methods: Patients with HRþ/HER2- metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFR1 nonamplified, 11q13 amplified, and (iii) FGFR1 and 11q13 nonamplified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 amplification (≥4 CNV) than those without high amplification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HRþ/ HER2- MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.-
dc.languageeng-
dc.relation.ispartofClinical Cancer Research-
dc.titleLucitanib for the treatment of HR<sup>þ</sup>/HER2<sup>-</sup> Metastatic breast cancer: Results from the multicohort phase II FINESSE study-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-19-1164-
dc.identifier.pmid31619444-
dc.identifier.scopuseid_2-s2.0-85076132296-
dc.identifier.volume26-
dc.identifier.issue2-
dc.identifier.spage354-
dc.identifier.epage363-
dc.identifier.eissn1557-3265-
dc.identifier.isiWOS:000507311000006-

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