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Clinical Cancer Research : An Official... Apr 2023In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).
PATIENTS AND METHODS
Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), or trastuzumab and an AI (Arm B). Induction chemotherapy was at investigator discretion. Primary endpoint: PFS. Key secondary endpoints: overall survival (OS) and safety.
RESULTS
Median PFS was 20.6 versus 15.8 months in Arms A and B, respectively (stratified HR, 0.67; P = 0.006). Median OS was 60.2 versus 57.2 months (stratified HR, 1.05; P = 0.78). Pertuzumab treatment effect was potentially enhanced in patients with no induction chemotherapy (26.6 vs. 12.5 months). Any-grade adverse events (AE) occurred in 122 patients per arm (96.1% vs. 98.4%); grade ≥ 3 AEs in 72 (56.7%) and 51 (41.1%); serious AEs in 46 (36.2%) and 28 (22.6%).
CONCLUSIONS
The PFS benefit of pertuzumab was maintained and OS was similar between arms at final analysis. Adding pertuzumab may enhance activity in patients who do not require first-line chemotherapy for M/LABC. No new safety concerns were reported. These data provide additional evidence of the role of first-line pertuzumab and trastuzumab in HER2-positive M/LABC.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Aromatase Inhibitors; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36716289
DOI: 10.1158/1078-0432.CCR-22-1092 -
Adherence to Oral Anticancer Medications Among Women With Breast Cancer in Africa: A Scoping Review.JCO Global Oncology Jan 2023Oral anticancer medications (OAMs) improve treatment outcomes and survival in women with breast cancer (BC). However, adherence to OAM therapy remains suboptimal. This... (Review)
Review
PURPOSE
Oral anticancer medications (OAMs) improve treatment outcomes and survival in women with breast cancer (BC). However, adherence to OAM therapy remains suboptimal. This scoping review provides evidence of adherence to OAMs among African women with BC.
METHODS
We searched four databases and gray literature, using guidance from the Joanna Briggs Institute. Thirteen studies on adherence rates, determinants, and interventions were included. NVivo 12 software was used to perform thematic analysis of the included studies. The determinants (barriers and facilitators) associated with adherence were analyzed according to the five dimensions of the WHO multidimensional adherence model.
RESULTS
Most studies (n = 11, 85%) focused on endocrine medication. Depending on the definition, measurements, and assessment period, the nonadherence rates ranged from 4.3% to 65.4% for endocrine medications, 80.9% for cytotoxic chemotherapies, and 32.7% for combined medications. The significant barriers associated with adherence include Islamic religion, concurrent comorbidities, mastectomy, anastrozole treatment, side effects, unawareness of treatment insurance coverage, and seeking treatment from traditional healers. Thorough therapeutic communication regarding treatment, neoadjuvant chemotherapy, and adequate social support significantly facilitate adherence. A randomized controlled trial of breast nursing interventions reported improved patient adherence.
CONCLUSION
The evidence mapped from studies that evaluated OAM adherence in women with BC indicates that nonadherence to OAMs is common. Applying context-specific standardized measures to assess adherence and facilitators or strategies targeting the identified barriers can optimize adherence and treatment outcomes. Effective interventions to improve adherence are limited. Therefore, further empirical and interventional studies in Africa are required to enhance the evidence.
Topics: Humans; Female; Breast Neoplasms; Medication Adherence; Mastectomy; Africa; Randomized Controlled Trials as Topic
PubMed: 36689700
DOI: 10.1200/GO.21.00289 -
Indian Journal of Surgical Oncology Dec 2022The aim of this study was to evaluate the clinico-pathological behaviour and treatment patterns of low-grade serous carcinomas (LGSC) of ovary treated at a regional...
The aim of this study was to evaluate the clinico-pathological behaviour and treatment patterns of low-grade serous carcinomas (LGSC) of ovary treated at a regional cancer centre. A retrospective analysis was done for the histopathology-proven cases of low-grade serous ovarian carcinoma, treated at a tertiary cancer institute between January, 2010, and September, 2019. There were 28 patients identified from the medical records with low-grade serous ovarian carcinoma. Median age of the patients was 43 years [22-79 years]. Average BMI was 22.3 ± 4.0 kg/m [range 15.2-31.2]. Twenty-one (75%) were parous and 7 (25%) were non-parous women. Median CA125 level was 188 IU/ml [range 6-14,187 IU/ml]. Ten (35.7%) patients had primary surgery elsewhere and 8 (80%) out of these patients had to undergo repeat staging. Fertility sparing surgery (FSS) was offered to 4 (14.3%) patients. Five (17.8%) patients had received neoadjuvant chemotherapy for advanced disease and poor performance status. Almost 82.2% (23) of the patients had no macroscopic residual disease at the primary surgery. According to International Federation of Obstetrics and Gynaecologists (FIGO) stage for ovarian carcinoma, there were 7 (25%), 6 (21.4%), 13 (46.4%), and 2 (7.1%) patients in the stages I, II, III, and IV respectively. Post-operative adjuvant chemotherapy was offered to 7 (25%), hormonal therapy (anastrozole/tamoxifen) to 7 (25%), and rest of 14 (50%) patients were under surveillance. Median follow-up time for the study group was 36 months. Overall survival (OS) and disease-free survival (DFS) at 2 years was 96.4% and 89.1%, respectively. Low-grade serous carcinomas of ovary differ biologically from high-grade serous ovarian carcinoma. Surgery is the cornerstone of the treatment. Further research is needed to understand the behaviour of these tumours for effective treatment strategies in future.
PubMed: 36687250
DOI: 10.1007/s13193-022-01543-5 -
Annals of Surgical Oncology Apr 2023The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to... (Randomized Controlled Trial)
Randomized Controlled Trial
Local-Regional Recurrence After Neoadjuvant Endocrine Therapy: Data from ACOSOG Z1031 (Alliance), a Randomized Phase 2 Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women with Estrogen Receptor-Positive Clinical Stage 2 or 3 Breast Cancer.
BACKGROUND
The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to neoadjuvant chemotherapy (NCT) after 4 weeks of receiving NAI with Ki67 greater than 10% increases pathologic complete response (pCR) in postmenopausal women with estrogen receptor-enriched (Allred score 6-8) breast cancer (BC).
METHODS
The study enrolled 622 women with clinical stage 2 or 3 estrogen receptor-positive (ER+) BC. Cohort A comprised 377 patients, and cohort B had 245 patients. The analysis cohort consisted of 509 patients after exclusion of patients who did not meet the trial eligibility criteria, switched to NCT or surgery due to 4-week Ki67 greater than 10%, or withdrew before surgery. Distribution of time to local-regional recurrence (LRR) was estimated using the competing-risk approach, in which distant recurrence and second primaries were considered to be competing-risk events. Patients who died without LRR, distant recurrence, or a second primary were censored at the last evaluation.
RESULTS
Of the 509 patients, 342 (67.2%) had breast-conserving surgery (BCS). Of 221 patients thought to require mastectomy at presentation, 50% were able to have BCS. Five (1%) patients had no residual disease in the breast or nodes at surgery. Among 382 women alive at this writing, 90% have been followed longer than 5 years. The 5-year cumulative incidence rate for LRR is estimated to be 1.53% (95% confidence interval 0.7-3.0%).
CONCLUSIONS
Rarely does NAI result in pCR for patients with stage 2 or 3 ER+ BC. However, a significant proportion will have downstaged to allow for BCS. Local-regional recurrence after surgery is uncommon (1.5% at 5 years), supporting the use of BCS after NAI.
Topics: Female; Humans; Letrozole; Anastrozole; Breast Neoplasms; Neoadjuvant Therapy; Receptors, Estrogen; Ki-67 Antigen; Postmenopause; Mastectomy
PubMed: 36653664
DOI: 10.1245/s10434-022-12972-5 -
Frontiers in Oncology 2022Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural...
BACKGROUND
Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage.
METHODS
The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through analysis.
RESULTS
The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of -7.5, -7.9, and -7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound's absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski's rule of five.
CONCLUSIONS
The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.
PubMed: 36591523
DOI: 10.3389/fonc.2022.950835 -
Frontiers in Oncology 2022Cystic brain metastases (CBM) in patients with breast cancer are rare. They have a worse prognosis than solid brain metastases, and they are less sensitive to...
Abemaciclib plus fulvestrant for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with cystic brain metastases: A case report and literature review.
Cystic brain metastases (CBM) in patients with breast cancer are rare. They have a worse prognosis than solid brain metastases, and they are less sensitive to radiotherapy. We report a case of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer with CBM. The patient underwent treatment with docetaxel combined with capecitabine for 5 months, followed by anastrozole maintenance therapy for 10 months, and palbociclib combined with exemestane for 22 months. CBM emerged and bone metastases increased in number. A missense mutation in (exon 10, c.1633G>A [p.Glu545Lys]) was detected by whole-exome next-generation sequencing from peripheral blood samples. After whole-brain radiotherapy (40 Gy/20 fx) combined with 3 months of treatment with everolimus and fulvestrant, CBM demonstrated partial remission (PR), but extracranial bone metastases continued to increase in number. Thus, the patient underwent fourth-line treatment with abemaciclib (100 mg bid) combined with fulvestrant (500 mg). Three months later, CBM significantly demonstrated PR and extracranial bone metastases were stable. At present, the patient has above 9 months of progression-free survival time without obvious adverse effects. This is the first report of abemaciclib combined with fulvestrant in the treatment of CBM in a patient with HR+/HER2- breast cancer.
PubMed: 36531067
DOI: 10.3389/fonc.2022.984454 -
Current Opinion in Obstetrics &... Feb 2023In spite of their rarity when considered individually, the sum of all rare ovarian tumours (ROT) represent almost half of all ovarian malignancies. As such, their... (Review)
Review
PURPOSE OF REVIEW
In spite of their rarity when considered individually, the sum of all rare ovarian tumours (ROT) represent almost half of all ovarian malignancies. As such, their appropriate inclusion within dedicated clinical trials is essential for enhanced management.
RECENT FINDINGS
Supported by institutional expert national (e.g. TMRG) and international (e.g. ESGO) networks and owing to national (e.g. ARCAGY-GINECO) and international (e.g. ENGOT) collaborations dedicated to clinical research, the last few years have shown increased number of clinical trials dedicated to ROT. These either were based on specific molecular features of ROT (e.g. expression of oestrogen receptors for low-grade serous ovarian carcinomas and anastrazole evaluation in the PARAGON trial) or on the evaluation of innovative therapies (e.g. pembrolizumab within the ROT cohort from the AcSé Pembrolizumab multicentric basket trial). Furthermore, recent years have also shown the advent of randomized clinical trials. For instance, the ALIENOR trial positioned weekly paclitaxel as a new option for relapsed sex cord-stromal tumours, while the GOG281/LOGS trial raised trametinib as a new standard-of-care option for recurrent low-grade serous carcinomas.
SUMMARY
The last few years have exhibited a paradigm shift towards the possibility to develop dedicated trials for ROT, owing to international collaborations supported by institutional networks. Current trials, molecular-driven and based on innovative designs, are highly promising, as they may bring ROT management towards more personalized medicine.
Topics: Female; Humans; Ovarian Neoplasms; Paclitaxel; Anastrozole; Cystadenocarcinoma, Serous; Precision Medicine
PubMed: 36440753
DOI: 10.1097/GCO.0000000000000836 -
Clinical and Translational Science Feb 2023Microdosing is a strategy to obtain knowledge of human pharmacokinetics prior to Phase I clinical trials. The most frequently used method to extrapolate microdose...
Microdosing is a strategy to obtain knowledge of human pharmacokinetics prior to Phase I clinical trials. The most frequently used method to extrapolate microdose (≤100 μg) pharmacokinetics to therapeutic doses is based on linear extrapolation from a noncompartmental analysis (NCA) with a two-fold acceptance criterion between pharmacokinetic metrics of the extrapolated microdose and the therapeutic dose. The major disadvantage of NCA is the assumption of linear extrapolation of NCA metrics. In this study, we used a naïve pooled data (NPD) modeling approach to extrapolate microdose pharmacokinetics to therapeutic pharmacokinetics. Gemcitabine and anastrozole were used as examples of intravenous and oral drugs, respectively. Data from microdose studies were used to build a parent-metabolite model for gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) and a model for anastrozole. The pharmacokinetic microdose models were extrapolated to therapeutic doses. Extrapolation of the microdose showed differences in pharmacokinetic shape for gemcitabine and dFdU between the simulated and observed therapeutic concentrations, whereas the observed therapeutic concentrations for anastrozole were captured by the extrapolation. This study demonstrated the possible use and feasibility of an NPD modeling approach for the evaluation and application of microdose studies in early drug development. Last, physiologically-based pharmacokinetic modeling might be an alternative for microdose extrapolation of drugs with complex pharmacokinetics such as gemcitabine.
Topics: Humans; Anastrozole; Gemcitabine; Administration, Intravenous; Clinical Protocols; Drug Development; Dose-Response Relationship, Drug
PubMed: 36419385
DOI: 10.1111/cts.13446 -
Molecular Oncology Jan 2023Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of...
Ribosome biogenesis-based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group.
Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) and Anastrozole (A, aromatase inhibitor) improves the progression-free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome. We evaluate for the first time the usage of ribosome biogenesis (RiBi) factors as a source of innovative markers. Using 47 FFPE tumours (A n = 18; V + A n = 29), 32 blood samples (A n = 13; V + A n = 19) and 30 samples of total RNAs (A n = 12; V + A n = 18) from the VICTORIA clinical trial, we observed an association between RiBi-associated markers and drug activity or prediction of treatment response. NOP10 and NHP2 mRNA levels were significantly higher in non-responders compared to responders in the Vistusertib + Anastrozole arm (P = 0.0194 and P = 0.0002 respectively; i.e. 8 weeks progression-free survival as endpoint). This study provides RiBi-based markers relevant for a better selection of patients with advanced endometrial carcinoma by predicting the response of endocrine therapy combined with mTOR inhibitor.
Topics: Humans; Female; Anastrozole; Nitriles; Triazoles; Aromatase Inhibitors; Biomarkers; TOR Serine-Threonine Kinases; Endometrial Neoplasms; Ribosomes; Breast Neoplasms; Antineoplastic Agents, Hormonal
PubMed: 36370117
DOI: 10.1002/1878-0261.13340 -
Cancer Diagnosis & Prognosis 2022Utilizing an experimental animal model, we investigated the correlation between aromatase inhibitors (AIs) (anastrozole and letrozole) and Calprotectin levels. AIs have...
BACKGROUND/AIM
Utilizing an experimental animal model, we investigated the correlation between aromatase inhibitors (AIs) (anastrozole and letrozole) and Calprotectin levels. AIs have demonstrated superior efficacy when used as adjuvant endocrine therapy or monotherapy for postmenopausal patients with hormone receptor (HR)-positive early-stage breast cancer, although various side effects have been recorded.
MATERIALS AND METHODS
Fifty-five adult female Wistar rats were randomized and assigned into four groups. The control group received no intervention. The other three groups were subjected to ovariectomy, and serum Calprotectin levels were measured at baseline, 2, and 4 months. In addition, glucose, total cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, low-density lipoprotein (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, and triglyceride levels were measured. Histological analysis of liver tissue was carried out following rats' euthanasia.
RESULTS
Aromatase inhibitors (anastrozole and letrozole) affect calprotectin levels in ovariectomized rats. Calprotectin, a marker of inflammation, was found to be affected by the use of the inhibitors.
CONCLUSION
The potential of hepatotoxicity can be examined by assessing the elevation of inflammation markers such as Calprotectin, which is an indicator that should be strictly taken into consideration when administering aromatase inhibitors as treatment.
PubMed: 36340459
DOI: 10.21873/cdp.10167