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1.
Gan To Kagaku Ryoho ; 46(8): 1311-1313, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501377

RESUMO

An 84-year-old woman had locally advanced sigmoid colon cancer that was unresectable because of deep invasion in the left pelvic wall. Transverse double-barrel colostomy was performed owing to stenosis in the sigmoid colon. The patient's performance status score was 2, and it was difficult to administer cytotoxic chemotherapy. Single-agent panitumumab chemotherapy was initiated. In addition, although S-1 was administered for 4 days in the fourth cycle, it was discontinued owing to drug intolerance. Panitumumab was administered seven times. The tumor size markedly reduced, and sigmoid colectomy was performed. Thus, single-agent panitumumab chemotherapy is a possible treatment option for advanced colorectal cancer in elderly patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Panitumumabe/uso terapêutico , Neoplasias do Colo Sigmoide , Idoso de 80 Anos ou mais , Colo Sigmoide , Feminino , Humanos , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia
2.
Medicine (Baltimore) ; 98(36): e16937, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490377

RESUMO

Metadherin (MTDH), also known as astrocyte elevated gene-1 (AEG-1), is an oncoprotein closely related to the development of breast cancer. However, few studies have been done on the expression and clinical significance of MTDH in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients.This study aimed to investigate the expression of MTDH in locally advanced HER-2 positive breast cancer, and evaluate the clinical significance of MTDH in predicting the prognosis of patients with HER-2 positive advanced breast cancer who received the neoadjuvant chemotherapy plus trastuzumab.In 144 HER-2 positive breast cancer tissues, 79 cases showed high expression of MTDH and 65 cases showed low expression. The expression of MTDH in locally advanced HER-2 positive breast cancer tissues was correlated with TNM stage, lymph node metastasis, Miller-Payne (MP) grade, and pathologic complete response (pCR) status (P < .05), but was not correlated with patient age, estrogen receptor (ER) expression level, progesterone receptor (PR) expression level, and Ki-67 expression level (P > .05). Kaplan-Meier univariate analysis revealed a negative correlation between MTDH expression and the disease-free survival (DFS) and overall survival (OS) in the post-operative patients with locally advanced HER-2 positive breast cancer (log rank test: P < .001). By using the COX proportional hazard regression model, it was found that MTDH expression, TNM stage, lymph node metastasis, and Ki-67 expression were closely related to DFS in patients. The hazard ratio (HR) of high MTDH expression was 1.816 (95% CI: 1.165-2.829). In addition, MTDH expression, TNM stage, and lymph node metastasis were also closely related to the OS of patient. The HR of the high expression of MTDH was 2.512 (95% CI: 1.472-4.286). The expression of MTDH in tumor tissues of patients with HER2-positive locally advanced breast cancer was significantly elevated, which was related to the poor pathological features.High MTDH expression was closely correlated with poor prognosis of patients and was an important factor affecting tumor progression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/biossíntese , Receptor ErbB-2/biossíntese , Trastuzumab/uso terapêutico , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese
3.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
4.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
5.
Anticancer Res ; 39(9): 4995-5001, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519606

RESUMO

BACKGROUND/AIM: Adoptive transfer of tumor-infiltrating lymphocytes (TILs) combined with non-myeloablative chemotherapy (NMA) has been shown to prolong survival in patients with metastatic disease. MATERIALS AND METHODS: Tissue harvesting was performed form a variety of sites. TILs were isolated, expanded and infused with bolus high-dose IL-2. RESULTS: Between 2008 and 2018, 242 lesions were resected for TILs harvesting from a range of sites form 196 patients without mortality and with minimal morbidity. Of those harvested, 75 were unable to complete therapy because of clinical deterioration during the wait period. Of 121 evaluable treated patients, there was no effect of metastatic site biopsied on the mean fold TIL expansion. Those receiving prior ipilimumab had a higher TIL fold expansion but a lower TIL fold expansion than those exposed to anti-PD1 therapy. CONCLUSION: Harvesting may be safely performed with successful TIL expansion from most sites. Prior check point inhibitory immunotherapy may potentially influence TIL fold expansion.


Assuntos
Imunoterapia Adotiva , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Melanoma/terapia , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto Jovem
6.
Anticancer Res ; 39(9): 5195-5201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519633

RESUMO

BACKGROUND/AIM: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and anti-programmed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. MATERIALS AND METHODS: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. RESULTS: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). CONCLUSION: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/sangue , Biomarcadores Tumorais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
7.
J Cancer Res Clin Oncol ; 145(10): 2625-2631, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492984

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICIs) are effective against a wide variety of cancers. However, they also induce a plethora of unique immune-related adverse events (irAEs). Since for many organ systems symptoms can be unspecific, differential diagnosis with progression of disease or infection may be difficult. C-reactive protein (CRP) has been suggested as a marker for infection. The purpose of this study was to evaluate the diagnostic value of CRP in differentiating infectious causes from autoimmune side effects induced by ICIs. METHODS: In order to investigate the role of CRP in irAEs, we screened our patient data base. Only events with full infectious workup were included. In total 88 events of irAEs in 37 melanoma patients were analyzed. CRP levels before and during irAEs were evaluated. Statistical analyses were conducted using the Chi-square test for categorical variables. RESULTS: At the onset of irAE, CRP rose in 93% of cases to a mean of 52.7 mg/L (CI 35.1-70.3) from 8.4 mg/L at baseline (normal < 5 mg/L) (P < 0.0001). Other causes of CRP elevation including infectious diseases were excluded, and procalcitonin (PCT) levels were normal in 92% of events. Importantly, in 42% of cases CRP elevations preceded clinical symptoms. CONCLUSION: CRP elevation can predict the onset of irAEs in patients treated with ICIs in the absence of infectious disease.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Biomarcadores , Proteína C-Reativa , Imunomodulação , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Adulto Jovem
8.
J Cancer Res Clin Oncol ; 145(9): 2303-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31396700

RESUMO

BACKGROUND: Since 1997, several monoclonal antibodies (mAbs) targeting the same receptor or its ligand have been approved for use in oncology. However, no studies have summarized head-to-head trials of these mAbs. METHODS: Systematic search of the biomedical literature and ClinicalTrials.gov for randomized studies comparing mAbs targeting the same receptor or its ligand that have been completed and published, completed and unpublished, or ongoing. We extracted trial characteristics including phase, indication, enrollment or target enrollment, randomization, primary endpoint and sponsor. RESULTS: Twenty-two approved cancer mAbs had at least one other approved mAb targeting the same receptor or its ligand, totaling 41 different oncology indications. These include 5 anti-CD20 mAbs, 5 anti-PD1/PDL1 mAbs, 4 anti-HER2 mAbs, 3 anti-EGFR mAbs, 3 anti-VEGF mAbs and 2 anti-IL6/IL6R mAbs. Seventeen were completed and published and 14 were unpublished or ongoing trials. The completed and published trials enrolled 11,373 patients and tested 13 mAbs (13/22, 59%). Additionally, 13 (76%) contained drugs manufactured by the same company and 13 (76%) reached conclusions felt to be favorable to the sponsor. Of the 14 ongoing/completed unpublished trials, there is a total target enrollment of 3404 patients with 9 mAbs tested. Of these, 86% (12/14) are testing mAbs manufactured by the same company and 71% (10/14) are sponsored by the company that made the drug being tested. CONCLUSIONS: Most trials test drugs manufactured or sponsored by the same company. An overview of clinical trials agenda may lead to more uniform testing, helping clinicians make better evidence-informed prescribing decisions.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Aprovação de Drogas , Humanos , Neoplasias/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
10.
J Surg Oncol ; 120(4): 786-793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368160

RESUMO

BACKGROUND AND OBJECTIVES: The single-arm ROSiA study evaluated frontline bevacizumab for advanced ovarian cancer. We explored how discordant surgically and radiologically assessed postoperative residual disease affects outcomes. METHODS: After debulking surgery, 1021 patients received 4 to 8 cycles of carboplatin-paclitaxel plus bevacizumab until progression or up to 24 months. The primary endpoint was safety; progression-free survival (PFS) was a secondary endpoint. We performed post hoc exploratory PFS analyses in four subgroups: surgeon-reported no visible residuum (NVR) without target lesions; surgeon-reported NVR with target lesions; macroscopic (≤1 cm) residuum; and >1 cm residuum. RESULTS: Surgical and radiological assessments were concordant in 94% of patients; 61 patients (6%; 21% of those with surgeon-reported NVR) had NVR with target lesions. Median PFS was numerically longest in patients with concordant surgically/radiologically assessed NVR (35.5 months), intermediate for surgeon-reported NVR with target lesions (31.8 months), and shortest for visible residuum (27.9 and 20.2 months for visible residuum ≤1 and >1 cm, respectively). One-year and 2-year PFS rates showed the same pattern. CONCLUSIONS: These analyses suggest that prognosis is potentially worse in patients with radiologically detected target lesions despite surgeon-reported NVR compared with concordant NVR by both assessment methods. Postsurgical imaging may add valuable prognostic information.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasia Residual/mortalidade , Neoplasias Ovarianas/mortalidade , Cirurgiões/estatística & dados numéricos , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Antineoplásicos Imunológicos/uso terapêutico , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Feminino , Seguimentos , Humanos , Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida
12.
Ceska Slov Farm ; 68(2): 43-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331174

RESUMO

Targeted therapy is a significant benefit in the treatment of cancer patients. Bevacizumab improves overall survival (OS) and progression free survival (PFS) in the treatment of metastatic colorectal cancer (mCRC). The clinical effectiveness of bevacizumab is similar to its efficacy in randomised controlled trials. However, the costs of bevacizumab treatment as well as other agents of targeted treatment are discussed between the health care payers, the regulatory authorities and the members of professional societies. Biomarkers of bevacizumab treatment helpful in the selection of eligible groups of patients are still missing. This review focuses on current bevacizumab therapy of mCRC from the pharmacoeconomic perspective. The cost per a 14-day bevacizumab treatment cycle is approximately 31,000 CZK in the Czech Republic. External published pharmacoeconomics analyses have no clear conclusions. Their results are usually expressed as the cost per QALY gained in comparison with a comparator. They differ according to the economic situation of the particular countries. The pharmacoeconomic results have to be confirmed in the real clinical practice, and then the decision should be reassessed by using the uniform methodology, e.g. the Health Technology Assessment (HTA).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Anticorpos Monoclonais , Neoplasias Colorretais/patologia , Análise Custo-Benefício , República Tcheca , Humanos , Metástase Neoplásica/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida
13.
Anticancer Res ; 39(7): 3419-3422, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262864

RESUMO

As part of the Pharmacology & Molecular Mechanisms (PAMM) Group, European Organization for Research and Treatment on Cancer (EORTC) 2019 winter Meeting Educational sessions, special focus has been placed on strategies to be undertaken to reduce the attrition rate when developing immune-oncology drugs. Immune checkpoint inhibitors have been game-changing drugs in several settings over the past decade such as melanoma and lung cancer. However, during the last years a rising number of studies failing to further improve clinical outcome in patients with cancer was recorded. Extensive pharmacometrics such as pharmacokinetics/pharmacodynamics modeling support should help to overcome the current glass ceiling that has apparently been reached with immuno-oncology drugs (IOD). In particular, it should help in the issue of setting up combinatorial regimen (i.e. combining immune checkpoint inhibitors with cytotoxics, anti-angiogenesis or targeted therapies) that can no longer be addressed when following standard trial-and-error approaches, but rather by using mathematical-derived algorithms as decision-making tools by investigators for rational design. In routine clinical setting, developing therapeutic drug monitoring of immune checkpoint inhibitors with adaptive dosing strategies has been a long-neglected strategy. Still, substantial improvements might be achieved using dedicated tools for precision medicine and personalized medicine in immunotherapy.


Assuntos
Antineoplásicos Imunológicos/farmacocinética , Animais , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Farmacologia Clínica/métodos
14.
Anticancer Res ; 39(7): 3887-3892, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262917

RESUMO

BACKGROUND/AIM: Pembrolizumab was approved as second-line treatment for patients with metastatic urothelial cancer (UC) in Japan. We performed a retrospective pilot study to assess the potency of pembrolizumab treatment in Japan. PATIENTS AND METHODS: The medical records of 40 consecutive Japanese patients with metastatic UC who started pembrolizumab between January and October 2018 were reviewed and statistically analyzed to clarify the efficacy and safety of the drug. RESULTS: The objective response rate, median progression-free survival period, and median overall survival period were 20.6%, 4.1 months and 10.0 months, respectively. Multivariate analysis indicated the presence of liver metastasis, worse performance status (≥2), and higher C-reactive protein as factors predictive of shorter OS. CONCLUSION: We demonstrated for the first time, a comparable efficacy and safety profile of pembrolizumab for Japanese patients with metastatic UC, as in the KEYNOTE-045 study. The results indicate the features of pembrolizumab therapy in the current Japanese clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/patologia
15.
Anticancer Res ; 39(7): 3945-3947, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262925

RESUMO

BACKGROUND/AIM: Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. CASE REPORT: We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. CONCLUSION: Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Antirreumáticos/uso terapêutico , Artrite Juvenil/induzido quimicamente , Artrite Juvenil/tratamento farmacológico , Criança , Feminino , Humanos , Metotrexato/uso terapêutico , Esteroides/uso terapêutico , Resultado do Tratamento , Uveíte/induzido quimicamente
16.
Anticancer Res ; 39(7): 3961-3965, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262928

RESUMO

BACKGROUND/AIM: Immune check point inhibitors (ICIs) are changing cancer treatment in several malignancies, including non-small cell lung cancer (NSCLC). The introduction of these active new agents is associated with a relevant increase of costs and it is, therefore, important to create a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as overall survival (OS). This analysis was conducted to assess the pharmacological costs of first- and second-line treatments with ICIs (pembrolizumab, nivolumab and atezolizumab) for metastatic NSCLC. MATERIALS AND METHODS: The present evaluation was restricted to phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in OS. RESULTS: Six phase III RCTs were evaluated. Concerning first-line, the lowest cost per month of OS-gain was associated with the use of pembrolizumab at 2,734 €. Concerning second-line, the lowest cost per month of OS-gain was associated with the use of atezolizumab at 3,724 €. CONCLUSION: Pembrolizumab and atezolizumab are cost-effective in both first and second-line treatment for metastatic NSCLC, respectively.


Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais/economia , Antineoplásicos Imunológicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/economia , Nivolumabe/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Anticancer Res ; 39(7): 3971-3973, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262930

RESUMO

BACKGROUND/AIM: Biosimilar agents are biologic products that have no clinically meaningful differences in terms of quality, efficacy, safety and immunogenicity compared to an already approved reference biological product, with the potential to reduce the costs of biologics. Considering the increasing numbers of oncology biosimilars, it is important to calculate the economic impact of biosimilars in oncology and hemathology, considering trastuzumab and rituximab as examples, with their greatest budgetary impact in Oncology and Hematology Units, respectively. The present analysis was conducted to assess the pharmacological costs of trastuzumab and rituximab originator versus the corresponding approved biosimilars. MATERIALS AND METHODS: Pivotal phase III randomized controlled trials (RCTs) were considered for the approved indications in neoadiuvant breast cancer (BC) and in first-line treatment for advanced follicular lymphoma. Pharmacological costs necessary to get the benefit in the cancer outcomes: i) time to treatment failure (TTF) and ii) pathological complete response (pCR) in biosimilars and originators were calculated. The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). RESULTS: Our analysis evaluated 5 phase III RCTs, including 2,362 patients. The economic advantage of biosimilars versus (vs.) originator is 274 € (rituximab) and from 3,283 € to 6,310 € (trastuzumab) per month for TTF (about 40% less than the originator). CONCLUSION: Combining pharmacological costs of drugs with the measure of efficacy represented by TTF and pCR, biosimilars of rituximab and trastuzumab are cost-effective treatments for advanced follicular lymphoma and breast cancer.


Assuntos
Antineoplásicos Imunológicos/economia , Medicamentos Biossimilares/economia , Rituximab/economia , Trastuzumab/economia , Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Hematologia/economia , Humanos , Oncologia/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Trastuzumab/uso terapêutico
18.
Rev Med Chil ; 147(3): 275-280, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344163

RESUMO

BACKGROUND: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. AIM: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. PATIENTS AND METHODS: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. RESULTS: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. CONCLUSIONS: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.


Assuntos
Macroglobulinemia de Waldenstrom/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Chile/epidemiologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/mortalidade
19.
Cancer Treat Rev ; 78: 17-30, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325788

RESUMO

INTRODUCTION: Immune checkpoint inhibitors, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in several types of cancer. In this review we summarize published and ongoing studies on checkpoint inhibitors in pancreatic cancer (PC). METHODS: We conducted a systematic literature search using Medline and Embase up to November 2018; additional data from a search on clinicaltrials.gov were included. Endpoints of interest encompassed overall survival (OS), progression free survival (PFS) and response rates. RESULTS: Full-length articles constituted a minority of included records. Furthermore, few patients were enrolled, and only few phase II studies were identified. Disappointing limited activity was demonstrated with single-agent checkpoint inhibitors in PC. A small number of studies on combination therapy showed promise with regards to response. But overall, PC patients treated with checkpoint inhibitors were not shown to elicit improvement in response rates or overall survival. CONCLUSION: Checkpoint inhibition monotherapy has failed to elicit efficacy in patients with pancreatic cancer. Combination regimens including chemotherapy have shown initial promise, but these results need to be verified. Numerous studies on checkpoint inhibition in PC are ongoing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Genes cdc , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia
20.
Cancer Sci ; 110(9): 2711-2721, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294893

RESUMO

The percentage of programmed death ligand 1 (PD-L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti-PD-1/PD-L1 therapy in lung cancer. PD-L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD-L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD-L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD-L1 expression was negative in 169 patients (73.2%), 1%-49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD-L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD-L1 expression was associated with high-grade cancer cells and in higher stage cancer. PD-L2 was negative in 109 patients (47.2%), 1%-49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD-L2-positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty-five patients (15.2%) were positive for both PD-L1 and PD-L2, whereas 81 patients (35.1%) were negative for both PD-L1 and PD-L2. Log-rank analysis showed that progression-free survival and overall survival were significantly the longest in the PD-L1-negative and PD-L2-positive groups (P < .0001 and P = .0120). We observed lower PD-L1 or PD-L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD-L1 or PD-L2 expression specifically in cancer cells.


Assuntos
Adenocarcinoma de Pulmão/patologia , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/análise , Neoplasias Pulmonares/patologia , Proteína 2 Ligante de Morte Celular Programada 1/análise , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imuno-Histoquímica/métodos , Pulmão/citologia , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Resultado do Tratamento
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