7 research outputs found
Lucitanib for the treatment of HR+/HER2- metastatic breast cancer:results from the multicohort phase II FINESSE study
No full textPurpose: The FGFR1 gene is amplified in 14% of patients with HR+/HER2− breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed.Patients and Methods: Patients with HR+/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 HR+/HER2− MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit.</p
Dutch national immunization schedule: compliance and associated characteristics for the primary series.
No full textIn the Netherlands, the recommended priming immunization schedule for diphtheria, tetanus, pertussis and polio (DTaP-IPV) is at 2, 3 and 4 months of age. We evaluated the compliance with the recommended schedule, as well as its characteristics. We included all infants born between 2007 and 2012 who received minimally one DTaP-IPV vaccination (n = 1,061,578). Infants complied with the schedule if they received the first vaccination between 6 and 9 weeks of age, and the second and third vaccination 2-6 weeks after the first and second vaccination. We examined associations between compliance and several characteristics using log-binomial regression. Compliance for the first, second and third vaccination was 81.6, 88.3 and 84.2%, respectively. Compliance with the total recommended schedule was 64.5%, and increased from 60.1% for 2007 to 68.5% for 2012. Compliance was higher for full-term infants (65.9%), infants with normal birth weight (66.0%) and when both parents were born in the Netherlands (66.8%)
Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative.
No full textAURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Table S1, Table S2; Figure S1, Figure S2, Figure S3, Figure S4, Figure S5 from Lucitanib for the Treatment of HR<sup>+</sup>/HER2<sup>−</sup> Metastatic Breast Cancer: Results from the Multicohort Phase II FINESSE Study
No full textSupplementary Table S1. Treatment dose, duration, interruption and reduction. Supplementary Table S2A. Performance of the FGF23 ELISA, Kainos Laboratories Inc., cat# CY4000. Supplementary Table S2B. Concentration range of FGF23 in serum and plasma samples. Supplementary Table S2C. ddPCR assays used for determination of FGFR1 CNV. Supplementary Figure S1. A) FINESSE study design. B) Supplementary Figure S1B. FINESSE CONSORT diagram. Supplementary Figure S2. FISH screening results for FGFR1, CCND1/11q and FGF3,4,19. All samples were screened for both FGFR1 and CCND1/11q. Only samples positive for CCND1/11q amplification were assessed for FGF3,4,19 amplification. Of these, 1 patient was not assessed for FGF3,4,19 at the request of the site. 3 patients assessed as FGF3,4,19 amplified by additional evalution criteria to those described in the Methods section, with >50% of tumour cells showing {greater than or equal to}5 gene signals/nucleus. Supplementary Figure S3. Progression-free survival by A) FGFR1 amplification status by FISH and B) FGFR1 expression by IHC. Supplementary Figure S4. Expression of endothelial FGF2 and Ki67 presented by trial cohort. Supplementary Figure S5. Progression free survival by A) endothelial FGF2 and B) endothelial Ki67 expression.</p
Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer.
No full textPURPOSE: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment. METHODS: Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values <.05 were statistically significant for the primary end point. All secondary end points were descriptive. RESULTS: One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; P = .022; ACT: -1.3 [95% CI, -2.3 to -0.2]; P = .017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; P = .017; ACT: -1.3 [95% CI, -2.4 to -0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status. CONCLUSION: Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients
Supplementary file - liver genes from Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative
No full textSupplementary file with the listing of the liver genes excluded from transcriptomic analyses.</p
Supplementary methods, tables and figures. from Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative
No full textFile with the supplementary material & methods, supplementary tables and supplementary figure.</p
