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1.
J Clin Oncol ; 42(2): 192-204, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38039427

RESUMO

PURPOSE: The addition of checkpoint inhibitors to first-line treatment has prolonged survival of patients with non-small-cell lung cancer (NSCLC), but prognosis remains poor, with new treatment options needed. Canakinumab, a human, monoclonal anti-interleukin (IL)-1ß antibody, has potential to enhance the activity of PD-L1 inhibitors and chemotherapy (CT) by inhibiting protumor inflammation. METHODS: CANOPY-1 was a phase III, randomized, double-blind study comparing canakinumab (200 mg subcutaneously once every 3 weeks) versus placebo, both combined with pembrolizumab (200 mg intravenously once every 3 weeks) and platinum-based doublet CT, as first-line treatment for advanced/metastatic NSCLC without EGFR or ALK mutations. The primary end points were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included overall response rate, safety, and patient-reported outcomes. RESULTS: Overall, 643 patients were randomly assigned to canakinumab (n = 320) or placebo (n = 323). With a median study follow-up of 6.5 months, the median PFS was 6.8 months with canakinumab versus 6.8 months with placebo (hazard ratio [HR], 0.85; 95% CI, 0.67 to 1.09; P = .102). With a median study follow-up of 21.2 months, the median OS was 20.8 months with canakinumab versus 20.2 months with placebo (HR, 0.87; 95% CI, 0.70 to 1.10; P = .123). No unexpected safety signals were observed for canakinumab combination. Infection rates were comparable between treatment and control arms. A higher frequency of neutropenia and ALT increase (grade ≤2) were reported in the treatment arm. Higher baseline C-reactive protein and IL-6 levels were associated with shorter PFS and OS. Patients treated with canakinumab had clinically meaningful delays in deterioration of lung cancer symptoms, including chest pain and coughing per LC13 and dyspnea per LC13 and C30. CONCLUSION: The addition of canakinumab to first-line pembrolizumab and CT did not prolong PFS or OS in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
2.
Breast Cancer Res Treat ; 203(3): 497-509, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37938495

RESUMO

PURPOSE: To assess whether erythropoiesis-stimulating agents (ESA) administration impacts the outcomes of patients with HER2-positive early breast cancer (EBC). METHODS: ALTTO (NCT00490139) patients were categorized by ESA use during adjuvant anti-HER2 treatment. Disease-free-survival (DFS), overall survival (OS), and time-to-distant recurrence (TTDR) were analyzed by ESA administration, with subgroup analyses according to prognostic factors. Log-rank tests and Cox modeling were performed. Adverse events (AEs) of ESA-interest were compared. RESULTS: Among 8381 patients recruited in ALTTO, 123 (1.5%) received ESA concomitantly with study treatment. The median age of patients receiving ESA was 54 years, 39.0% premenopausal, most had tumor size > 2 cm (56.9%), node-positive (58.5%), and positive estrogen receptor expression (61.8%). Median follow-up was shorter in the ESA group [6.1 years (IQR 5.3-7.0) vs. 6.9 years (6.0-7.1); p < 0.001]. There was no DFS difference by ESA administration (log-rank p = 0.70), with 3- and 7-year DFS of 89.2% (95% CI 81.8-93.8%) and 81.6% (71.4-88.5%) in ESA group vs. 88.3% (87.6-89.0%) and 80.0% (79.1-80.9%) in No-ESA group. In subgroup analyses, the interaction of ESA administration with menopausal status was statistically significant (unadjusted p = 0.024; stratified p = 0.033), favoring premenopausal women receiving ESA. We observed no significant association of ESA administration with OS (log-rank p = 0.57; 7-year OS in ESA 88.6% vs. 90.0% in non-ESA) or TTDR. ESA-interest AEs were experienced by eight (6.5%) patients receiving ESA and 417 (5.1%) in the No-ESA group (p = 0.41). CONCLUSION: ESA administration to patients receiving adjuvant anti-HER2 treatment for HER2-positive EBC was safe and not associated with a negative impact on survival outcomes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Trastuzumab/efeitos adversos , Receptor ErbB-2/metabolismo , Eritropoese , Resultado do Tratamento , Intervalo Livre de Doença , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
Br J Cancer ; 127(10): 1799-1807, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36050448

RESUMO

BACKGROUND: Patients with small node-negative HER2-positive breast cancer are commonly treated with paclitaxel and 1 year of adjuvant trastuzumab. We performed a sub-analysis of the ALTTO trial to explore the long-term outcomes of patients with small node-negative tumours. METHODS: The ALTTO trial randomised 8381 patients with early HER2-positive BC treated with adjuvant chemotherapy (anthracycline/taxane- or taxane/carboplatin-based), to trastuzumab (T), lapatinib (L), their sequence (T → L) or their combination (L + T). Patients with tumours ≤3 cm and node-negative were included in this sub-analysis. RESULTS: A total of 2821 patients were analysed (median follow-up of 7 years). The median age was 52 years, and most patients had tumours ≤2 cm (64.3%). The 7-year disease-free survival (DFS) was 88.1% (95% CI: 86.7-89.3%). DFS was similar for arms T, T + L and T⟶L and significantly lower for arm L (stratified log-rank P = 0.031). The 7-year overall survival rate was 95.9% (95% CI: [95.0-96.6%) and the 7-year time-to-distant recurrence was 93.4% (95% CI: 92.3-94.4%). CONCLUSION: With most patients treated with anthracycline-based regimens, ALTTO shows that patients with small tumours treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes, similar to those of the APT trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00490139.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Receptor ErbB-2 , Taxoides/uso terapêutico , Trastuzumab
5.
Clin Breast Cancer ; 22(4): 308-318, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34980541

RESUMO

BACKGROUND: Beta-2 adrenergic receptor (ß2AR) modulates immune activation and may enhance trastuzumab activity. We assessed the impact of ß2AR gene (ADRB2) expression on the outcomes of patients with HER2-positive early-stage breast cancer enrolled on the NCCTG-N9831 trial. PATIENTS AND METHODS: This is a post-hoc analysis of the NCCTG-N9831 trial, which compared chemotherapy (arm A) versus chemotherapy plus trastuzumab (arms B&C) as adjuvant treatment of patients with HER2-positive early-stage breast cancer, with disease-free survival (DFS) as primary endpoint. Gene expression levels retrieved by DASL assay were used to classify patients as ADRB2-high or ADRB2-low. Hazard ratios (HRs) were calculated by a Cox proportional model adjusted for prognostic variables and ADRB2 expression. Correlations between ADRB2 expression and stromal tumor-infiltrating lymphocyte (TIL) levels were assessed with Pearson coefficient. A multivariable Cox regression model with interaction term was performed to assess the interaction between ADRB2 expression and treatment arm; and ADRB2 expression and a 8-gene signature previously shown to predict trastuzumab benefit. RESULTS: Overall, 1,282 patients were included (ADRB2-high [N = 944] / ADRB2-low [N = 338]). A high expression of ADRB2 was associated with a longer DFS (P = .01) in the overall population. The addition of trastuzumab to chemotherapy improved DFS only in patients with ADRB2-high tumors (P < .01). ADRB2 expression was correlated with TIL levels (r = 0.24, P < .001). No association between ADRB2 expression and the 8-gene trastuzumab benefit signature was observed (P = .32). CONCLUSION: Our findings suggest that a high ADRB2 expression is a favorable prognostic factor and may identify patients with HER2-positive early-stage breast cancer who benefit from adjuvant trastuzumab. TRIAL REGISTRATION: clinicaltrials.gov NCT00005970.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Receptor ErbB-2/metabolismo , Receptores Adrenérgicos beta 2/genética , Trastuzumab/uso terapêutico
6.
BMC Cancer ; 21(1): 1292, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856936

RESUMO

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. METHODS AND ANALYSIS: Oncodistinct 004 - AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. ETHICS AND DISSEMINATION: The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03674424).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Humanos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Neoplasias da Bexiga Urinária/patologia , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Gencitabina
7.
Breast ; 59: 183-192, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273666

RESUMO

BACKGROUND: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. METHODS: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. RESULTS: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03-4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49-0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23-6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93-7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69-7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33-4.10; p < 0.001). CONCLUSIONS: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Linfócitos do Interstício Tumoral , Recidiva Local de Neoplasia , Prognóstico , Receptor ErbB-2
8.
J Bras Pneumol ; 47(3): e20200378, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33656100

RESUMO

OBJECTIVE: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. METHODS: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. RESULTS: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. CONCLUSIONS: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Vinorelbina/uso terapêutico
9.
AIDS ; 35(4): 605-618, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33394680

RESUMO

BACKGROUND: As women living with HIV (WLWH) become older, their risk of developing breast cancer increases. Nonetheless, literature is conflicting regarding tumor stage, distribution of subtypes and overall survival among WLWH vs. HIV-negative women with breast cancer. We assessed differences in clinicopathological characteristics and overall survival between these two groups. METHODS: Systematic review and meta-analysis using MEDLINE, Scopus, ISI Web of Knowledge, LILACS, SciELO and conference abstracts up to 1 January 2020. Cross-sectional/cohort studies comparing baseline characteristics (stage and/or subtypes) and/or overall survival of WLWH vs. HIV-negative women with breast cancer were included. We performed random-effects meta-analyses to estimate summary statistics and subgroup analyses according to region of the world. RESULTS: Eighteen studies [4 from North America, 14 from sub-Saharan Africa (SSA)] were included, with 3174 WLWH and 2 394 598 HIV-negative women. WLWH from North America and SSA were more likely to present with stage III/IV disease compared with HIV-negative women - pooled odds ratio (pOR) 1.76 [95% confidence interval (CI):1.58-1.95] and pOR 1.23 (95% CI: 1.06-1.42), respectively. WLWH from SSA were also less likely to have estrogen receptor-positive/HER2-negative tumors (pOR 0.81; 95% CI: 0.66-0.99). After adjustment, WLWH had worse overall survival compared with HIV-negative women, both in North America [pooled adjusted hazard ratio (aHR) 2.45; 95% CI: 1.11-5.41] and SSA (aHR 1.43; 95% CI: 1.06-1.92). CONCLUSION: Compared with HIV-negative women, WLWH are diagnosed with breast cancer at a more advanced stage and have a worse overall survival. These results should raise awareness regarding the detection and survival gap among WLWH with breast cancer and further studies are needed to decipher the reasons behind these disparities.


Assuntos
Neoplasias da Mama , Infecções por HIV , HIV-1 , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , América do Norte
10.
J Natl Cancer Inst ; 113(4): 462-470, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32750143

RESUMO

BACKGROUND: There are limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer, especially in patients treated with endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors. METHODS: A pooled analysis of individual patient-level data from MONARCH 2 and 3 trials was performed. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2) and divided into 2 treatment groups: abemaciclib + ET vs placebo + ET. The primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate, adverse events according to BMI, and loss of weight (≥5% from baseline) during treatment. RESULTS: This analysis included 1138 patients (757 received abemaciclib + ET and 381 placebo + ET). There was no difference in PFS between BMI categories in either group, although normal-weight patients presented a numerically higher benefit with abemaciclib + ET (Pinteraction = .07). Normal and/or underweight patients presented higher overall response rate in the abemaciclib + ET group compared with overweight and/or obese patients (49.4% vs 41.6%, odds ratio = 0.73, 95% confidence interval = 0.54 to 0.99) as well as higher neutropenia frequency (51.0% vs 40.4%, P = .004). Weight loss was more frequent in the abemaciclib + ET group (odds ratio = 3.23, 95% confidence interval = 2.09 to 5.01). CONCLUSIONS: Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight or obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal and/or underweight patients compared with overweight and/or obese patients. More studies analyzing body composition parameters in patients under treatment with cyclin-dependent kinase 4/6 inhibitors may further clarify this hypothesis.


Assuntos
Aminopiridinas/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Benzimidazóis/uso terapêutico , Índice de Massa Corporal , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Benzimidazóis/efeitos adversos , Neoplasias da Mama/patologia , Intervalos de Confiança , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Fulvestranto/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Obesidade/epidemiologia , Razão de Chances , Sobrepeso/epidemiologia , Placebos/uso terapêutico , Intervalo Livre de Progressão , Magreza/epidemiologia , Redução de Peso
11.
J. bras. pneumol ; J. bras. pneumol;47(3): e20200378, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1154705

RESUMO

ABSTRACT Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.


RESUMO Objetivo: A quimioterapia adjuvante melhora a sobrevida de pacientes com câncer pulmonar de células não pequenas (CPCNP) ressecado. No entanto, o esquema cisplatina-vinorelbina está relacionado com risco significativo de toxicidade clinicamente relevante. Nosso objetivo foi avaliar a eficácia, segurança e viabilidade da quimioterapia adjuvante para pacientes com CPCNP em um cenário de mundo real. Métodos: Estudo retrospectivo de coorte realizado em um único centro com pacientes com CPCNP em estágio I-III submetidos a cirurgia com intuito curativo entre 2009 e 2018. A quimioterapia adjuvante foi administrada a critério dos médicos. Os pacientes foram divididos em dois grupos: quimioterapia adjuvante e sem quimioterapia adjuvante (grupo controle). Os desfechos estudados foram sobrevida global (SG) e sobrevida livre de recidiva (SLR), bem como o perfil de segurança e viabilidade do esquema cisplatina-vinorelbina em um cenário de mundo real. Resultados: O estudo envolveu 231 pacientes, 80 dos quais receberam quimioterapia adjuvante. Destes, 55 receberam o esquema cisplatina-vinorelbina. As análises de sobrevida estratificadas pelo estágio do tumor mostraram que os pacientes com CPCNP em estágio II que receberam quimioterapia adjuvante apresentaram melhor SLR (p = 0,036) e SG (p = 0,017) do que os do grupo controle. Entre os pacientes com CPCNP em estágio III que receberam quimioterapia adjuvante, a SLR foi melhor (p < 0,001) e houve uma tendência a melhor SG do que no grupo controle (p = 0,060). Dos que receberam o esquema cisplatina-vinorelbina, 29% apresentaram neutropenia febril de grau 3-4, e 9% morreram em virtude de toxicidade. Conclusões: Os resultados confirmam o efeito benéfico da quimioterapia adjuvante em pacientes com CPCNP em um contexto real. No entanto, o esquema cisplatina-vinorelbina relacionou-se com taxas alarmantes de toxicidade e alternativas mais eficazes e menos tóxicas devem ser investigadas.


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Cisplatino/efeitos adversos , Quimioterapia Adjuvante , Vinorelbina/uso terapêutico , Estadiamento de Neoplasias
12.
Artigo em Inglês | MEDLINE | ID: mdl-33334819

RESUMO

OBJECTIVES: Although systemic chemotherapy is often administered to patients with malignant bowel obstruction (MBO), its benefit remains unknown. This study assessed the outcomes of patients who received systemic chemotherapy as part of MBO treatment. METHODS: For this retrospective cohort study, data were extracted from records of patients hospitalised due to MBO in a tertiary cancer centre from 2008 to 2020. Eligible patients were not candidates for surgery and received systemic chemotherapy targeting the underlying malignancy causing MBO. Primary objective was to assess patient outcomes after chemotherapy; secondary objectives were rates of intestinal function recovery, hospital discharge and grade ≥3 toxicities. The primary endpoint was overall survival (OS). RESULTS: A total of 167 patients were included: median age was 55 (18-81) years, 91% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 75.5% had gastrointestinal tumours and 70% were treatment-naive. The median OS after chemotherapy was 4.4 weeks (95% CI 3.4 to 5.5) in the overall population. No OS difference was observed according to treatment line (p=0.24) or primary tumour (p=0.13). Intestinal function recovery occurred in 87 patients (52%), out of whom 21 (24.1%) had a reobstruction. Hospital discharge was possible in 74 patients (44.3%). Grade≥3 adverse events occurred in 26.9% of the patients, and a total of 12 deaths (7%) attributed to toxicities were observed after chemotherapy. CONCLUSIONS: MBO was associated with a dismal prognosis in this mostly treatment-naive population. The administration of chemotherapy yielded a significant risk of toxicities, whereas it did not appear to provide any relevant survival benefit in this scenario.

14.
ESMO Open ; 5(6): e000979, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33154022

RESUMO

BACKGROUND: In HER2-positive breast cancer, time elapsed between completion of (neo)adjuvant trastuzumab and diagnosis of metastatic disease ('trastuzumab-free interval', TFI) is crucial to choose the optimal first-line treatment. Nevertheless, there is no clear evidence to support its possible prognostic role. METHODS: In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial, patients with HER2-positive early breast cancer were randomised to 1 year of either trastuzumab alone, lapatinib alone, their sequence or their combination. This exploratory analysis included only patients in the trastuzumab alone or trastuzumab plus lapatinib arms who developed a distant disease-free survival (DDFS) event. Overall survival (OS) was defined as time between date of DDFS event and death; age at diagnosis, tumour size and hormone receptor status were the variables included in the multivariate models. RESULTS: Out of 8381 patients included in ALTTO, 404 patients in the trastuzumab alone and trastuzumab plus lapatinib arms developed a DDFS event, of which 201 occurred <12 months (group A) and 203 >12 months (group B) after completion of adjuvant trastuzumab. No significant difference in location of first DDFS event was observed (p=0.073); a numerically higher number of patients in group A than in group B developed brain metastasis (26% vs 15%). Choice of first-line therapy differed between the two groups (p=0.022): in group A, more patients received lapatinib (25% vs 11%) and less pertuzumab (8% vs 17%). Median OS was 29.3 and 18.4 months in groups B and A, respectively (adjusted HR 0.69; 95% CI 0.54-0.89; p=0.004). The longer OS for patients in group B was observed across the analysed subgroups without interaction according to hormone receptor status (p=0.814) nor type of administered adjuvant anti-HER2 treatment (p=0.233). CONCLUSIONS: TFI has prognostic value in patients with HER2-positive early breast cancer treated with adjuvant trastuzumab-based therapy. TFI is a valid tool to better individualise clinical recommendations and to design future first-line treatment trials for metastatic patients.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapêutico , Trastuzumab/uso terapêutico
15.
Expert Rev Anticancer Ther ; 20(7): 563-573, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32536212

RESUMO

INTRODUCTION: Metronomic chemotherapy exerts its effects via inhibition of angiogenesis, immune modulation of the tumoral stroma, induction of senescence and apoptosis of tumor cells. Due to its favorable toxicity profile and its oral administration, metronomic chemotherapy arises as a promising alternative to be combined with endocrine therapy for the treatment of patients with luminal breast cancer. AREAS COVERED: The present manuscript reviews the rationale supporting the combination of metronomic chemotherapy and endocrine therapy, discussing the studies that evaluated this regimen in the treatment of early-stage and metastatic breast cancer patients. Finally, we conclude by providing an expert opinion on the current role and perspectives for the combination of metronomic chemotherapy and endocrine therapy in the management of patients with luminal breast cancer. EXPERT OPINION: Retrospective series and early-phase clinical trials have shown promising signs of activity and a favorable toxicity profile with this regimen, which warrants further investigation as a treatment option for luminal breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Administração Metronômica , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/patologia
16.
Crit Rev Oncol Hematol ; 149: 102940, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32252001

RESUMO

BACKGROUND: The role of adjuvant chemotherapy in biliary tract cancer is controversial. We performed a systematic review and meta-analysis to assess the effect of adjuvant chemotherapy in biliary tract cancer patients. METHODS: A literature search was performed to identify randomized controlled trials (RCTs) comparing adjuvant chemotherapy versus observation, and a pooled analysis was conducted using the random-effect model. RESULTS: Three RCTs (N = 866) were included. No difference was observed between chemotherapy and observation in terms of OS (HR 0.91; 95 %CI, 0.75-1.09; p = 0.295), whereas a significant improvement in RFS was shown (HR 0.83; 95 %CI, 0.69-0.99; p = 0.040). No subgroup that benefited most from adjuvant chemotherapy was identified, although a trend was observed in N+ patients (HR 0.83; 95 %CI, 0.65-1.08; p = 0.165). DISCUSSION: Adjuvant chemotherapy yields a significant RFS benefit in biliary tract cancer patients and should be considered for those who are able to tolerate additional treatment after surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias do Sistema Biliar/patologia , Intervalo Livre de Doença , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Breast Cancer Res Treat ; 181(1): 199-209, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246377

RESUMO

PURPOSE: Body composition parameters including muscle and adipose tissue measurements have emerged as prognostic factors in cancer patients. Besides cell cycle regulation, CDK 4 and 6 also control metabolic processes (lipid synthesis, glycolysis, and mitochondrial function). We studied the impact of baseline body composition parameters on response to CDK 4/6 inhibition and changes on body composition during treatment. METHODS: Retrospective study of 50 patients treated at Institut Jules Bordet between December 2016 and August 2019 with endocrine therapy and CDK 4/6 inhibitor as first or second-line treatment for metastatic breast cancer (BC). CT-based body composition analysis was performed at 3 time points. Cox regression and Kaplan-Meier method were used for the association with Progression-free survival (PFS). Changes in body composition parameters were described in means and compared using paired sampled T test. RESULTS: Baseline sarcopenia was present in 40% of patients and associated with a significantly worse PFS compared to patients without sarcopenia (20.8 vs 9.6 months, HR 2.52; 95% CI 1.02-6.19, p = 0.037). Patients with higher visceral fat index and higher visceral fat density had better PFS (20.8 vs 10.4 months, HR 0.40; 95% CI 0.16-0.99 p = 0.041-stratified for treatment line). No significant alterations in body composition parameters during treatment were observed. CONCLUSION: Sarcopenia is a potential early marker of poor prognosis among patients with metastatic BC treated with CDK 4/6 inhibitors. CT scan evaluation of sarcopenia and adiposity revealed significant prognostic information. Visceral fat could also play an important role in response to CDK 4/6 inhibitors, deserving further investigation.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Composição Corporal , Índice de Massa Corporal , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Tecido Adiposo/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Gordura Intra-Abdominal/fisiopatologia , Pessoa de Meia-Idade , Metástase Neoplásica , Obesidade/fisiopatologia , Prognóstico , Estudos Retrospectivos , Sarcopenia/fisiopatologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
18.
Clin Breast Cancer ; 20(3): 262-273.e7, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32229175

RESUMO

BACKGROUND: Beta-2 adrenergic receptor (ADRB2) mediates proliferation and treatment resistance in preclinical models of human epidermal growth factor receptor 2 positive (HER2+) breast cancer. We evaluated ADRB2 gene expression as a prognostic and predictive biomarker in patients with HER2+ early breast cancer. METHODS: ADRB2 expression was retrieved from HER2+ patients enrolled in the FinHer study (N = 202), and 2 public datasets containing data from patients with HER2+ early breast cancer: one including patients who did not receive systemic treatment (disease-free survival [DFS] dataset; n = 175) and another including patients who received neoadjuvant treatment (pathologic complete response [pCR] dataset; n = 207). Survival was estimated with Kaplan-Meier method and Cox regression was used for uni-multivariate analyses. ADRB2 expression was correlated with several gene signatures. RESULTS: ADRB2 high expression was associated with improved DFS rates in HER2+ patients (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.32-0.84; P = .0068). No association between ADRB2 expression and pCR was observed (odds ratio 1.14; 95% CI, 0.63-2.10; P = .67). No association between ADRB2 and relapse-free survival (RFS) was observed in HER2+ patients enrolled in the FinHer study (HR 0.93; 95% CI, 0.69-1.25; P = .61). ADRB2 was associated with a low expression of angiogenesis-related (vascular endothelial growth factor -0.38, P < .001) and proliferation-related (aurora kinase A -0.36, P < .001; genomic grade index -0.028, P < .001; signal transducers and activators of transcription -0.17, P < .001) genes; and a high expression of immune-related genes (Perez +0.45, P < .001; STAT1 +0.28, P < .001; immune response gene expression module +0.29, P < .001). CONCLUSIONS: Opposing our initial hypothesis, a high ADRB2 expression may be a favorable prognostic factor in patients with HER2+ early breast cancer. This association appears to be mediated by antiproliferative, antiangiogenic, and immunogenic effects of ADRB2.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Mama/patologia , Recidiva Local de Neoplasia/epidemiologia , Receptores Adrenérgicos beta 2/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/métodos , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Proteção , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores Adrenérgicos beta 2/análise , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Medição de Risco/métodos
19.
Clin Cancer Res ; 26(12): 2783-2788, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32046997

RESUMO

HER2+ early breast cancer is a heterogeneous disease, comprising all the intrinsic breast cancer subtypes. The only biomarker available nowadays for anti-HER2 treatment selection is HER2 status itself, but estrogen receptor (ER) status is emerging as a robust predictive marker within HER2+ disease. In this Perspective, we discuss the biological and clinical differences between patients with HER2+/ER-positive (ER+) disease versus those with HER2+/ER-negative (ER-neg) tumors, namely, short-term and long-term (>5 years after diagnosis) prognosis, response to neoadjuvant treatment and benefit from adjuvant anti-HER2-targeted therapies. We also address other possible biomarkers to be used for patient selection in future clinical trials, such as gene signatures, PAM50 subtypes, tumor-infiltrating lymphocytes, PIK3CA mutations, and changes in Ki67 score during treatment and discuss their limitations. Finally, we suggest new clinical trial designs that can have an impact on clinical practice, aiming to test treatment deescalation separately for patients with HER2+/ER+ and HER2+/ER-neg tumors. We also propose an integrated classification of HER2+ disease, comprising DNA, RNA, protein expression, and microenvironment characteristics, in order to identify those tumors that are truly "HER2-addicted" and may benefit the most from anti-HER2 treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico
20.
Breast ; 48 Suppl 1: S7-S20, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31839166

RESUMO

This review is focused on trials generating results that potentially impacted clinical practice since the 2017 St. Gallen Consensus; the most impactful trial was KATHERINE, which revealed a 11.3% absolute iDFS improvement with T-DM1 (compared to trastuzumab) in HER2-positive breast cancer patients who presented invasive residual disease following neoadjuvant treatment. These results, if reinforced by a subsequent overall survival benefit, will consolidate neoadjuvant treatment as the standard-of-care for most HER2-positive breast cancer patients. The addition of pertuzumab to adjuvant trastuzumab (APHINITY) or extending anti-HER2 therapy with 1 year of neratinib (ExteNET) also improved outcomes, but in a more modest way. In triple-negative early breast cancer patients presenting invasive residual disease after neoadjuvant chemotherapy, the CREATE-X trial demonstrated the benefit of post-neoadjuvant capecitabine. In patients with luminal tumours, updated results of the SOFT/TEXT trials confirmed the benefit of aromatase inhibitors plus ovarian suppression in high-risk premenopausal patients, and the 12-year results of the BIG1-98 trial demonstrated a sustained trend in favour of letrozole compared to tamoxifen in the adjuvant treatment of postmenopausal patients. The TAILOR-X study showed that, overall, patients with an intermediate recurrence risk score (11-25) in the OncotypeDX 21-gene assay did not benefit from adjuvant chemotherapy. A meta-analysis performed by the EBCTCG demonstrated that extended adjuvant aromatase inhibitors modestly reduced breast cancer recurrence risks, with a more pronounced benefit in patients previously treated with tamoxifen. Finally, an EBCTCG meta-analysis including patients with all breast cancer subtypes showed that dose-dense chemotherapy improved survival when compared to conventionally-timed chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/tendências , Ado-Trastuzumab Emtansina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Intervalo Livre de Doença , Detecção Precoce de Câncer , Feminino , Humanos , Metanálise como Assunto , Quinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/efeitos dos fármacos , Tamoxifeno/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento
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