Purpose
CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer ...(ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC.
Methods
Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL).
Results
Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment.
Conclusion
Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2– ABC.
Trial registration
linicalTrials.gov NCT02941926.
Background In node-positive breast cancer patients at diagnosis (cN +) that render node-negative after neoadjuvant systemic treatment (NAST), axillary lymph node dissection (ALND) can be avoided in ...selected cases. Axillary ultrasound (AUS) is most often used for re-staging after NAST. We aimed to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AUS after NAST for predicting nodal response at the Institute of Oncology, Ljubljana. Methods Biopsy-confirmed cN + patients consecutively diagnosed at our institution between 2008 and 2021, who received NAST, followed by surgery were identified retrospectively. Only patients that underwent AUS after NAST were included. AUS results were compared to definite nodal histopathology results. We calculated sensitivity, specificity, PPV and NPV of AUS. We also calculated the proportion of patients with false-positive AUS that results in surgical overtreatment (unnecessary ALND). Results We identified 437 cN + patients. In 244 (55.8%) AUS after NAST was performed. Among those, 42/244 (17.2%) were triple negative (TN), 78/244 (32.0%) Her-2 positive (Her-2 +), and 124/244 (50,8%) luminal Her-2 negative cancers. AUS was negative in 179/244 (73.4%), suspicious/positive in 65/244 (26.6%) (11/42 (26.2%) TN, 19/78 (24.4%) Her-2 + , and 35/124 (28.2%) luminal Her-2 negative cancers). On definite histopathology, nodal complete response (pCR) was observed in 89/244 (36.5%) (19/42 (45.2%) TN, 55/78 (70.5%) Her-2 + , and 15/124 (12.1%) luminal Her-2 negative cancers). Among patients with suspicious/positive AUS, pCR was observed in 20/65 (30.8%) (6/11 (54.5%) TN, 13/19 (68.4%) Her-2 + and 1/35 (2.9%) luminal Her-2 negative cancers). Sensitivity was 29.0%, specificity 77,5%, PPV 69.2%, NPV 38.5%. Specificity and PPV in TN was 68.4% and 45.4%, in Her-2 + 76.4% and 31.6%, in luminal Her-2 negative 93,3% and 97,1%, respectively. Conclusion In approximately half of the patients, AUS falsely predicts nodal response after NAST and may lead to overtreatment in 30% of the cases (ALND). However, AUS has to be interpreted in context with tumor subtype. In luminal Her-2 negative cancers, it has a high PPV and is therefore useful. Keywords: Breast cancer, Neoadjuvant therapy, Axillary ultrasound, Axillary staging, Sentinel lymph node biopsy
Triple negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesteron (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2). Our ...retrospective analysis addressed prognostic factors for short- and long-term outcomes of patients (pts) with TNBC pts treated in routine clinical practice. PATIENT AND METHODS.: Our retrospective study included 269 TNBC treated at Institute of Oncology Ljubljana between March 2000 and December 2006. The collected data included patients', tumours' and treatments' characteristics. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis.
The median age of our patients was 55.3 yrs (23-88.5) and the median follow-up was 5.9 yrs (0.3-9.6). Six (2%) pts experienced local only, 79 (92%) pts distal recurrence and 66 (24%) died. The predominant localisation of the first relapse was in visceral organs (70.4%). The 5-year disease-free survival (DFS) for the entire group was 68.2% and the 5-year overall survival (OS) was 74.5%. We found a pattern of high recurrence rate in the first 3 years following the diagnosis and a clear decline in recurrence rate over the next 3 years. In the univariate analysis age, nodal status, size and lymphovascular invasion (LVI) were found to have a significant impact on DFS as well as on OS. In the multivariate analysis only age (HR=1.79; 95%CI=1.14-2.82; p=0.012) and nodal status (HR=2.71; 95%CI=1.64-4.46; p<0.001) retained their independent prognostic value for DFS and for OS only the nodal status (HR=2.96; 95%CI=1.51-5.82; p=0.002).
In our series of TNBC pts nodal status and age (older than 65 yrs) were found to be independent prognostic factors for DFS, whereas for OS only the nodal status. We found a pattern of a high recurrence rate in the first 3 years following the diagnosis and a decline in the recurrence rate over the next 3 yrs with higher rate of distal versus local recurrence and a predominant localization of distal metastases in visceral organs.
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Background: Alpelisib (A) is a PI3Kα-selective inhibitor and degrader which, in combination with fulvestrant, has been approved for the treatment of hormone receptor-positive (HR+), human ...epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC). Hyperglycemia is the most commonly observed adverse event of A. A pooled analysis of X2101 AND SOLAR-1 trials showed the association between five baseline patient characteristics (age, fasting plasma glucose (FPG), glycated haemoglobin, body mass index (BMI) and blood monocyte count (BMC)) and the development of A-induced hyperglycaemia (HG). We examined the association between baseline factors and the A-induced HG grade (G) ≥2 in a real-world setting. Methods: We performed the retrospective observational study and included patients (pts) with HR+, HER2-, PIK3CA-mutated metastatic breast cancer who received A + fulvestrant between Oct 18, 2019, and Oct 13, 2022, at the Institute of Oncology Ljubljana. Electronic records were reviewed. Baseline age, FPG, glycated haemoglobin, BMI and BMC before the start of A therapy and glucose levels during treatment with A were collected. Random plasma glucose values (RPG) were used for HG grading according to CTCAE V. The chi-square test was used to determine the association between the baseline characteristics and A-induced HG G ≥2. Results: Thirty-one female pts were included in the analysis. The median follow-up was 21 months, and the median duration of A treatment was 5.4 months. The baseline pts characteristics were as follows: median age 58 years (range 33–80), median FPG 5.6 mmol/L (range 3.10–8.6), median BMI 21.7 kg/m² (range 18.7–30.4), and median BMC was 10.3% (range 5.3–16.6). Baseline glycated haemoglobin values were only known for 58.1% of patients, so we did not further analyse them. The highest HG grades during treatment with A were as follows: G0 in 14 pts (45.2%), G1 in 5 pts (16.1%), G2 in 6 pts (19.4%), G3 in 6 pts (19.4 %). The calculated cut-off values associated with A-induced HG ≥2 were: age above 65 years, FPG above 5.9 mmol/L and BMC more than 11.5. None of the BMI cut-off values was associated with HG G≥2. Association between the baseline age, FPG and BMC and A-induced HG G≥2. Conclusions: Age over 65 years, FPG more than 5.9 mmol/L and BMC more than 11.5% have a statistically significant higher probability for A-induced HG G≥2. Therefore, these patients need more frequent blood glucose measurements, lifestyle adjustments and early treatment with metformin and/or other oral glucose-lowering agents. Table: see text
Abstract Background Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer ...(BC) best practices. A new targetable category termed ‘HER2-low’ has been identified in tumors previously classified as ‘HER2-negative’. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. Materials and methods An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. Results Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. Conclusions Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries.
The purpose of the study was to find out whether there is a difference in the early parameters of cardiotoxicity (left ventricular ejection fraction LVEF and N-terminal pro-B-type natriuretic peptide ...NT-proBNP) between the two groups of patients: the patients treated for left breast cancer (left breast cancer group) and those treated for the right breast cancer (right breast cancer group), after the treatment had been completed.
The study included 175 consecutive patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer, treated concurrently with trastuzumab and radiotherapy (RT), between June 2005 and December 2010. Echocardiography with LVEF measurement was performed before adjuvant RT (LVEF
) and after the completed treatment (LVEF
,). After the treatment NT-proBNP measurement was done as well. The difference (Δ) between LVEF
and LVEF
was analysed (Δ LVEF = LVEF
- LVEF
) and compared between the two groups.
There were 84 patients in the left and 91 in the right breast cancer group. Median observation time was 57 (37-71) months. Mean Δ LVEF (%) was -1.786% in the left and -2.607% in the right breast cancer group (p = 0.562, CI: -2.004 to 3.648). Median NT-proBNP were 111.0 ng/l in the left and 90.0 ng/l in the right breast cancer group (p = 0.545). Echocardiography showed that the patients in the left breast cancer group did not have significantly worse systolic and diastolic left ventricular function in comparison with the patients in the right breast cancer group, but, they had higher incidence of pericardial effusion (9 11% vs. 1 1%) (p = 0.007).
We did not find any significant differences in the early parameters of cardiotoxicity (LVEF, NT-proBNP) between the observed groups. Patients who received left breast/chest wall irradiation had higher incidence of pericardial effusion.
The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced ...breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.
Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured.
Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events.
These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.
Triple-negative breast cancer (TNBC) accounts for about 10-20% of all breast cancer cases and is associated with an unfavorable prognosis. Until recently, treatment options for TNBC were limited to ...chemotherapy. A new successful systemic treatment is immunotherapy with immune checkpoint inhibitors, but new tumor-specific biomarkers are needed to improve patient outcomes. Cannabinoids show antitumor activity in most preclinical studies in TNBC models and do not appear to have adverse effects on chemotherapy. Clinical data are needed to evaluate efficacy and safety in humans. Importantly, the endocannabinoid system is linked to the immune system and immunosuppression. Therefore, cannabinoid receptors could be a potential biomarker for immune checkpoint inhibitor therapy or a novel mechanism to reverse resistance to immunotherapy. In this article, we provide an overview of the currently available information on how cannabinoids may influence standard therapy in TNBC.
To assess real-world outcomes and prognostic factors of non-metastatic inflammatory breast cancer according to immunohistochemistry (IHC)-based subtype and treatment regimen.
An institutional ...retrospective analysis of patients treated with neoadjuvant systemic treatment (NAST) for stage III inflammatory breast cancer diagnosed between 2001 and 2018 was performed. The survival outcomes in relation to patient characteristics, tumour characteristics, treatment modality and response to NAST were analyzed.
225 patients fulfilled the inclusion criteria, 90% of patients were node-positive. IHC-based subtypes: 39.1% were HR+/HER2-, 19.1% HR+/HER2+, 23.1% HR-/HER2+ and 18.7% HR-/HER2-. Treatment was multimodal: NAST (100%), surgery (94.2%) and radiotherapy (94.2%). 53.3% of patients received adjuvant endocrine therapy, 34.3% (neo)adjuvant trastuzumab. Tri-modality therapy was applied in 89.3% of patients. Following NAST, a pathologic complete remission (pCR) in the breast was found in 16.9%, in the axilla in 29.7% and in both the breast and axilla in 10.3% of patients. The axillary pCR rate was significantly higher in HR- subtypes. Median overall survival (OS) was 8.9, 7.2, 5.8 and 2.3 years (p < 0.001) for HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- subtype, respectively. On multivariate analysis, IHC-based subtype, age and axillary pCR were found as independent prognostic factors for RFS and OS. pCR rate and median OS improved over time, 5.8% vs 14.7% and 4.7 vs 10.0 years (2001–2009 vs. 2010–2018), respectively.
Axillary pCR and the non-triple-negative IHC-based subtype are favourable prognostic factors for RFS and OS in inflammatory breast cancer. Introduction of taxanes and antiHER2 drugs contributed to improved pCR rate and OS.
•Immunohistochemistry-based subtype is independent prognostic factor for RFS and OS in inflammatory breast cancer.•Axillary pCR is independent prognostic factor for RFS and OS in inflammatory breast cancer.•Axillary pCR is higher in HR-inflammatory breast cancers.•Prognosis of inflammatory breast cancer improved due to more effective systemic therapy.
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