148 research outputs found
Implications of subcutaneous or intravenous delivery of trastuzumab: further insight from patient interviews in the PrefHer study
BACKGROUND: The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. METHODS: The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. RESULTS: 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). CONCLUSIONS: Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. EUDRACT NUMBER: 2010-024099-25
Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study
Aim
To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166).
Patients and methods
Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin ® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin ® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation.
Results
A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients).
Conclusions
Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected
A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC)
A unified definition of clinical anthracycline resistance breast cancer
The purpose of the study was to determine the response rates (RR) and duration to second- and third-line chemotherapy programmes in patients with anthracycline-resistant breast cancer, utilizing various definitions of anthracycline resistance. This was a retrospective analysis performed on 1335 patients with metastatic breast cancer who participated in consecutive clinical trials of first line, anthracycline-containing combination chemotherapy (ACCC) at the University of Texas MD Anderson Cancer Center between July 1973 and April 1980. Anthracycline-resistant groups were identified using definitions of anthracycline resistance found in the literature: progressive disease as best response to ACCC (Group 1, n = 56 patients); progressive disease while receiving ACCC after an intervening response to the drug (Group 2, n = 84); progressive disease within 6 months of last dose of ACCC (Group 3, n = 233); and progressive disease within 12 months of last dose of ACCC (Group 4, n = 272). Second- and third-line therapies administered to these patients included methotrexate, doxorubicin, mitoxantrone, bisantrene, vinblastine, vindesine, melphalan, mitomycin, cisplatin, etoposide and others, but not taxanes. The distribution of patients' characteristics was similar between the four groups, as was the use of second- and third-line regimens. Response rate (RR) to second-line chemotherapy were 5% and 7.7% for Group 1 and Group 2 respectively. In contrast, RR to second-line chemotherapy were 21.6% and 15% for Group 3 and 4. The differences in response rate between the combination of Groups 1 and 2 and Groups 3 or 4 were significant (P = 0.005 and P = 0.04 respectively). These results indicate that strictly defined anthracycline resistance as defined in Groups 1 and 2 is associated with resistance to many other cytotoxic drugs. The definitions used in Groups 3 and 4 include many patients with responsive tumours, and a more favourable prognosis. © 2000 Cancer Research Campaig
Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT).
BACKGROUND: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. METHODS: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. FINDINGS: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. INTERPRETATION: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. FUNDING: The National Institute for Health Research Health Technology Assessment programme
PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study
BACKGROUND: This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference
trastuzumab (Herceptin®) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line
treatment for HER2-positive metastatic breast cancer.
METHODS: Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014
plus paclitaxel (PF-05280014 group; n = 352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n = 355). PF-05280014 or
trastuzumab-EU was administered weekly (first dose 4 mg/kg, subsequent doses 2 mg/kg), with the option to change to a 3-weekly
regimen (6 mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression.
Paclitaxel (starting dose 80 mg/m2
) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal
benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and
confirmed by Week 33, based on blinded central radiology review.
RESULTS: The risk ratio for ORR was 0.940 (95% CI: 0.842–1.049). The 95% CI fell within the pre-specified equivalence margin of
0.80–1.25. ORR was 62.5% (95% CI: 57.2–67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3–71.4%) in the trastuzumab-EU
group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences
between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU
group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety
outcomes and immunogenicity were similar between the treatment groups.
CONCLUSION: When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel
demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT0198967
Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck
This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.co
Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study
PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance
A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers
HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism
Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer
BACKGROUND: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone (hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.61-0.93). We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL). PATIENTS AND METHODS: Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety. RESULTS: Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR=0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR=0.85, 95% CI 0.68-1.05) or OS (HR=0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected. CONCLUSION: In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS but no improvement in longer-term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life. CLINICALTRIALSGOV: NCT01250379
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