Abstract Backgound Neoadjuvant chemotherapy (CT) with anti-HER2 blockade using trastuzumab (H) and pertuzumab (P) is a standard of care for patients (pts) with HER2-positive early-stage Breast Cancer (eBC). Historically, taxanes (T) and anthracyclines (A) have been the mainstays of (neo)adjuvant CT in this setting, but the added benefit of A in the era of anti-HER2 therapy has been questioned. This study aimed to assess the effectiveness, cardiac safety, and cost-effectiveness of an anthracycline-free regimen (TCHP) in a real-world population of pts deemed unfit for A, compared to pts treated with the standard regimen of doxorubicin and cyclophosphamide plus dual-blockade associated with docetaxel (AC-DHP) at a single Portuguese Comprehensive Cancer Center. Methods This retrospective cohort study included a consecutive series of female eBC HER2+ pts who initiated primary treatment with TCHP between July 2018 and August 2022. The primary endpoint was pathological complete response (pCR), and secondary endpoints were cardiac safety and disease-free survival (DFS). The outcomes were compared with a historical database of eBC HER2+ pts who started primary treatment with AC-DHP between August 2015 and May 2021. Clinical data was collected from medical and administrative records. Descriptive statistics were used to describe categorical and continuous variables, and the Kaplan-Meier method was used for DFS analysis. Costs analysis employed the micro-costing technique, considering individual medical direct costs from diagnosis until surgery. Multivariate logistic regression models were used for effectiveness analysis and the gamma general model for costs analysis. The incremental cost-effectiveness ratio (ICER) was calculated using the pCR rate as a measure of effectiveness. Results A total of 233 and 23 pts were included in the TCHP and AC-DHP groups respectively. Reasons for choosing the anthracycline-free regimen in the TCHP group were primarily age-related frailty (52%), medical comorbidities (26%), and previous exposure to anthracyclines (22%). The TCHP pts were older (median age 71 years, range [45-77] vs. 47 years [24-70]) and had lower baseline Left Ventricular Ejection Fractions (LVEF) (median 65% [51-80] vs. 60% [56-73]), with a higher proportion of hormone receptor (HR) negative pts (78.3% vs. 33.0%). Clinical stages were balanced between groups, but the TCHP group had a higher nodal involvement (N+) (73.9% vs. 61.8%). The pCR rates were higher in the TCHP group (65.2% vs. 46.1%, HR 0.98 [95% CI 0.36 - 2.70]). Subgroup analysis by HR status showed comparable pCR rates: 77.1% vs. 74.1% in HR- pts and 40% vs. 39.7% in HR+ pts. Cardiac safety analysis indicated a median decrease in LVEF of 9% in both the TCHP and AC-DHP groups, with 43.5% of TCHP pts experiencing a decline of 10% or more, and 13.0% dropping below 50%. In comparison, these figures were 44.2% and 3.9%, respectively, in the AC-DHP group. At the end of the follow-up, only one patient in the TCHP group with a LVEF < 50% persisted with mild symptoms of chronic heart failure. The median follow-up time for DFS events, starting from surgery, was 31.1 months in the TCHP group and 45.7 months in the AC-DHP group, with 1-year DFS rates of 91.3% and 100%, respectively. The ICER analysis indicated that TCHP was cost-effective, as the incremental cost for achieving an additional pCR in similar subgroups can be outweighed by later cost savings, mainly due to further adjuvant treatment with trastuzumab instead of TDM-1. Conclusions In a real-world population of HER2+ eBC patients unfit for anthracyclines, the TCHP regimen demonstrated a higher overall pCR rate compared to a historical control treated with the AC-DHP regimen, along with an acceptable cardiac safety profile. These results support the broader use of the TCHP regimen in HER2+ eBC pts, as recommended by current NCCN guidelines. However, larger studies involving similar populations are needed to provide higher levels of evidence. Citation Format: Ricardo Pinto, Rita Calisto, Patrícia Redondo, Ana Silva, Pedro Castro, Rute Fernandes, Raquel Teixeira, Diana Mata, Ana Ferreira, Maria Bento, Cláudia Vieira. Real world outcomes of neoadjuvant therapy with Trastuzumab and Pertuzumab associated with carboplatin and docetaxel (TCHP) in HER2+ early breast cancer patients unfit for anthracyclines: a retrospective cohort comparative study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-02.
Abstract Background Anti-HER2 therapies are associated with a risk of cardiac toxicity, particularly as part of anthracycline-based regimens. BERENICE (NCT02132949), a nonrandomized, Phase 2 cardiac safety study showed neoadjuvant treatment with pertuzumab (P) + trastuzumab (H) and 2 common anthracycline–taxane-based regimens had a safety profile consistent with prior studies of P+H, and was associated with high pathologic complete response rates. Here we report safety data from the P+H adjuvant treatment period (AP). Methods Patients (pts) with centrally confirmed, localized HER2-positive breast cancer and normal cardiac function received 4 q2w dose-dense doxorubicin and cyclophosphamide cycles (60/600mg/m2) then 12 qw paclitaxel injections (80mg/m2; Cohort A), or 4 q3w fluorouracil/epirubicin/cyclophosphamide cycles (500/100/600 mg/m2) then 4 q3w docetaxel cycles (75mg/m2, up to 100mg/m2;Cohort B). In both cohorts, 4 q3w cycles of P (loading:840mg; maintenance:420mg) + H (loading:8mg/kg; maintenance:6mg/kg) were started with taxane therapy and continued in the adjuvant setting (for up to 13 cycles to complete 1 year of treatment). Surgery was scheduled after 8 cycles of preoperative therapy. Primary endpoints were incidence of New York Heart Association (NYHA) Class III/IV heart failure and incidence of left ventricular ejection fraction (LVEF) declines (≥10%-points from baseline to <50%; asymptomatic and symptomatic events) assessed by ECHO/MUGA. Confirmed LVEF declines were defined as significant LVEF declines at 2 consecutive visits. Results In total, 397 pts received ≥1 dose of study medication and were included in the overall treatment period (OTP) safety analysis. Of these, 371 (Cohort A:181; Cohort B:190) pts entered the AP and were included in the AP safety analysis. Mean (SD) number of AP treatment cycles of P and H were 12.3 (2.0) in Cohort A and 12.3 (2.2) in Cohort B. In the AP, incidence of heart failure was minimal (0.5%) and confirmed LVEF decline incidence was low (Table 1). Table 1: Cardiac AE Cohort ACohort B OTP n=199AP n=181OTP n=198OTP n=190NYHA Class III/IV heart failure Events, n4011Pts with event, n (%)3(1.5)01(0.5)1(0.5)LVEF decline Events, n36223429Pts with LVEF decline, n (%)21(10.6)14(7.7)22(11.1)20(10.5)Pts with confirmed LVEF decline, n (%)7(3.5)5(2.8)7(3.5)6(3.2) General adverse events (AEs) are shown in Table 2; 26 (14.4%) pts in Cohort A and 45 (23.7%) in Cohort B had diarrhea AEs (mostly grade 1). Table 2: General AE Cohort ACohort BPts, n (%)OTP n=199AP n=181OTP n=198AP n=190Any AE198(99.5)171(94.5)198(100.0)171(90.0)Grade ≥3 AE109(54.8)23(12.7)126(63.6)40(21.1)Serious AE54(27.1)15(8.3)61(30.8)17(8.9)AE leading to P or H discontinuation19(9.5)9(5.0)14(7.1)11(5.8) Conclusion P+H in the adjuvant setting, following P+H with anthracycline-based regimens in the neoadjuvant setting, are associated with low incidence of cardiac AEs. Cardiac safety results for P+H in the AP and OTP of BERENICE were consistent with results from prior studies evaluating adjuvant treatment with single-agent H, suggesting the addition of P to H in the adjuvant setting does not increase cardiac toxicity. Citation Format: Dang C, Ewer MS, Delaloge S, Ferrero J-M, Verrill M, Colomer R, Vieira C, de la Cruz Merino L, Lucas J, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Eng-Wong J, Swain SM. Safety of adjuvant treatment with pertuzumab plus trastuzumab after neoadjuvant anthracycline-based chemotherapy in patients with HER2-positive localized breast cancer: Updated results from the BERENICE study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-04.
e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.
Patient Safety is considered a serious public health problem. Very often patients suffer damage that could have been prevented or mitigated during their care. Family members and health professionals are also victims of this complex process. Communication is one of the 6 international safety goals in patient care and considered a very important one. The lack of integrated and effective communication processes between the various teams of professionals and health services are factors that contribute to the failure in care.
Introduction: Obstructive sleep apnea is a clinical entity that is associated with an increase in morbidity and mortality and it is estimated that it is significantly undiagnosed. The objective of this study was to assess the risk of undiagnosed obstructive sleep apneain obese individuals.Material and Methods: A descriptive and analytical cross-sectional study; the risk of obstructive sleep apnea’s was assessed over a period of 11 months by applying the STOP-Bang questionnaire to all individuals who attended a family health unit who were aged ≥ 18 years and had body mass index of ≥ 30 kg/m2 and who had not yet been diagnosed with obstructive sleep apnea and agreed to participate; the risk of an undiagnosed moderate to severe obstructive sleep apnea was considered for any STOP-Bang score of ≥ 3. Results: The risk of undiagnosed obstructive sleep apnea was assessed in 888 individuals (59.3% females) with an average age of 59.6 ± 14.68 years and a mean body mass index 33.6 ± 3.43 kg/m2; the mean STOP-Bang score was 3.5 ± 1.74, 70.9% scored ≥ 3; the frequency of all STOP-Bang questionnaire parameters was higher (p < 0.004) within the group with score ≥ 3.Discussion: The studied population is one of the main strengths, since it is in obese people that the incidence of this disease is higher. There are some limitations related to this sample coming from a single family health unit, as well as the patients’ follow-up being carried out throughout routine appointments for diseases that are closely related with obstructive sleep apnea.Conclusion: The level of underdiagnosis of obstructive sleep apnea’s in obese individuals can be significantly high and a large proportion of them may have the disease at a moderate to severe stage; Family Physicians can have a very important role in screening and diagnosis.
Serviço de Oncologia Médica. Instituto Português de Oncologia Francisco Gentil. Porto. Portugal. A 27-year-old man, smoker, presented with three months history of fever. A left pulmonary mass inseparable from the heart was identified and serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and immunohistochemistry of the biopsy specimen, in conjunction with the clinical findings were compatible with a diagnosis of pulmonary blastoma with germ cell differentiation. The tumour was considered unresectable. The patient was submitted to two cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was instituted, but progressive disease was identified after 2 cycles. Six months after the diagnosis cerebral metastases were found and the patient died. This case illustrates a rare situation of difficult diagnosis and treatment.
Osteoarthritis is a major cause of joint pain and disability, with the knee joint being the most commonly affected. The aim of this study is to investigate the evidence about the possible association between recreational running and the development of this pathology which is still controversial and sparse. Of the 409 articles in the initial research, four were included in this review. It was concluded that recreational running does not predispose to the development of clinical or radiographic knee osteoarthrosis, on the contrary, it seems to have a protective effect.
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