Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-32007366

RESUMO

PURPOSE: The standard of care in management of patients with good performance status and unresectable stage III non-small cell lung cancer (NSCLC) therapy is concurrent chemoradiation. Newer techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are replacing 3-dimensional conformal radiation (3DCRT) despite low-quality evidence of improved outcomes. We used population-based data to examine survival outcomes by radiation technique. METHODS AND MATERIALS: A population-based retrospective cohort of patients with stage III NSCLC treated with concurrent chemoradiation from 2009 to 2017 in Ontario were identified. The primary outcome was a comparison of overall survival among 3DCRT, IMRT, and VMAT, calculated using the Kaplan-Meier method and compared using log-rank test. Cox regression was used to investigate effect of radiation type on overall survival adjusted for other covariates. RESULTS: A total of 3872 patients were treated with 3DCRT (n = 1178), IMRT (n = 1847), or VMAT (n = 847). A decline in 3DCRT and increase in VMAT use were observed over time. Median survival in months was 21.2 (95% confidence interval [CI], 20.0-22.8) for 3DCRT, 23.9 (95% CI, 22.3-25.6) for IMRT, and 24.9 (95% CI, 22.5-27.4) for VMAT, but these differences were not statistically significant (P = .06). CONCLUSIONS: Our study demonstrates that survival is not compromised in patients receiving IMRT or VMAT (compared with 3DCRT). Thus, given the potential dosimetric advantages associated with these techniques, VMAT and IMRT are recommended for the management of patients with stage III NSCLC.

2.
J Clin Oncol ; : JCO1903022, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990617

RESUMO

PURPOSE: The aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) without driver alterations. A guideline update for patients with stage IV NSCLC with driver alterations will be published separately. METHODS: The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel made updated recommendations based on a systematic review of randomized controlled trials from December 2015 to 2019. RESULTS: This guideline update reflects changes in evidence since the previous guideline update. Five randomized controlled trials provide the evidence base. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS: Recommendations apply to patients without driver alterations in epidermal growth factor receptor or ALK. For patients with high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non-squamous cell carcinoma (non-SCC), the Expert Panel recommends single-agent pembrolizumab. Additional treatment options include pembrolizumab/carboplatin/pemetrexed, atezolizumab/carboplatin/paclitaxel/bevacizumab, or atezolizumab/carboplatin/nab-paclitaxel. For most patients with non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1, the Expert Panel recommends pembrolizumab/carboplatin/pemetrexed. Additional options are atezolizumab/carboplatin/nab-paclitaxel, atezolizumab/carboplatin/paclitaxel/bevacizumab, platinum-based two-drug combination chemotherapy, or non-platinum-based two-drug therapy. Single-agent pembrolizumab is an option for low positive PD-L1. For patients with high PD-L1 expression (TPS ≥ 50%) and SCC, the Expert Panel recommends single-agent pembrolizumab. An additional treatment option is pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel). For most patients with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%), the Expert Panel recommends pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy. Single-agent pembrolizumab is an option in select cases of low positive PD-L1. Recommendations are conditional on the basis of histology, PD-L1 status, and/or the presence or absence of contraindications. Additional information is available at www.asco.org/lung-cancer-guidelines.

3.
Oncologist ; 24(11): 1405-1409, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31315962

RESUMO

Trastuzumab is an effective treatment for HER2-positive breast cancer. Current guidelines recommend withholding trastuzumab in patients experiencing a significant asymptomatic decline in left ventricular function. In this commentary, we discuss the survival benefits afforded by trastuzumab juxtaposed against the risk of trastuzumab-mediated cardiotoxicity. It is not known whether the net benefit of continuing trastuzumab in the setting of mild cardiotoxicity outweighs the associated risks. We describe a potential approach undertaken by our group, and others, and call for a randomized trial.

6.
J Geriatr Oncol ; 10(3): 449-458, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30318328

RESUMO

OBJECTIVES: Small cell lung cancer (SCLC) represents a significant health burden. There is a lack of information about patterns of referral and treatment for older patients over 70 years of age, in comparison to younger patients with SCLC. MATERIALS AND METHODS: A population-based retrospective cohort study was undertaken for patients identified from the Ontario Cancer Registry, Canada. All cases of SCLC diagnosed between January 2000 and December 2010 were eligible. Data were extracted on demographic variables, treatment and outcome. Logistic regression analyses were performed as appropriate. RESULTS: There were 9021 cases of SCLC, with 10% of cases ≥80 years and 32.8% of cases aged 70-79 years and 53% male. Older patients were less likely to be referred to a medical oncologist (OR 0.28 ≥ 80 years, OR 0.60 70-79 years) and less likely to receive chemotherapy (OR 0.19 ≥ 80 years, OR 0.52 70-79 years) compared to younger patients (age < 70). Age, higher comorbidity and prior receipt of home care services were all prognostic of a lower likelihood of referral to a medical oncologist and receipt of chemotherapy. Local health region was also prognostic for referral to and receipt of chemotherapy, indicative of significant regional variation in practice. CONCLUSIONS: Older patients with SCLC are less likely to be referred for treatment and less likely to receive treatment than younger patients. These data represent a potential gap in knowledge translation.

8.
J Clin Oncol ; 35(30): 3484-3515, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28806116

RESUMO

Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development. Recommendations New or revised recommendations include the following. Regarding first-line treatment for patients with non-squamous cell carcinoma or squamous cell carcinoma (without positive markers, eg, EGFR/ALK /ROS1), if the patient has high programmed death ligand 1 (PD-L1) expression, pembrolizumab should be used alone; if the patient has low PD-L1 expression, clinicians should offer standard chemotherapy. All other clinical scenarios follow 2015 recommendations. Regarding second-line treatment in patients who received first-line chemotherapy, without prior immune checkpoint therapy, if NSCLC tumor is positive for PD-L1 expression, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab; if tumor has negative or unknown PD-L1 expression, clinicians should use nivolumab or atezolizumab. All immune checkpoint therapy is recommended alone plus in the absence of contraindications. For patients who received a prior first-line immune checkpoint inhibitor, clinicians should offer standard chemotherapy. For patients who cannot receive immune checkpoint inhibitor after chemotherapy, docetaxel is recommended; in patients with nonsquamous NSCLC, pemetrexed is recommended. In patients with a sensitizing EGFR mutation, disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mutation, then chemotherapy is recommended. Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Guias de Prática Clínica como Assunto , American Medical Association , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Medicina Baseada em Evidências/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Oncologia/métodos , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias , Nivolumabe , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sociedades Médicas , Estados Unidos
9.
J Clin Oncol ; 35(25): 2960-2974, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28437162

RESUMO

Purpose The panel updated the American Society of Clinical Oncology (ASCO) adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO convened an update panel and conducted a systematic review of the literature, investigating adjuvant therapy in resected non-small-cell lung cancers. Results The updated evidence base covered questions related to adjuvant systemic therapy and included a systematic review conducted by Cancer Care Ontario current to January 2016. A recent American Society for Radiation Oncology guideline and systematic review, previously endorsed by ASCO, was used as the basis for recommendations for adjuvant radiation therapy. An update of these systematic reviews and a search for studies related to radiation therapy found no additional randomized controlled trials. Recommendations Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections. For individuals with stage IB, adjuvant cisplatin-based chemotherapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a medical oncologist, is recommended to assess benefits and risks of adjuvant chemotherapy for each patient. The guideline provides information on factors other than stage to consider when making a recommendation for adjuvant chemotherapy, including tumor size, histopathologic features, and genetic alterations. Adjuvant chemotherapy is not recommended for patients with stage IA disease. Adjuvant radiation therapy is not recommended for patients with resected stage I or II disease. In patients with stage IIIA N2 disease, adjuvant radiation therapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a radiation oncologist, is recommended to assess benefits and risks of adjuvant radiation therapy for each patient with N2 disease. Additional information is available at www.asco.org/lung-cancer-guidelines and www.asco.org/guidelineswiki .


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Humanos , Neoplasias Pulmonares/patologia , Oncologia/métodos , Oncologia/normas , Estadiamento de Neoplasias , Radioterapia Adjuvante
10.
Clin Lung Cancer ; 18(5): 444-459.e1, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28416123

RESUMO

Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1-positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/secundário , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Nivolumabe , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
11.
Clin Lung Cancer ; 18(1): 68-76.e2, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28341109

RESUMO

INTRODUCTION: This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m2 days 1 to 3 plus LM (arm 1) or alone (arm 2). RESULTS: In the phase 1 study (n = 33), a dose of LM at 112 mg/m2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m2. In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug. CONCLUSION: The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CD56/química , Imunoconjugados/química , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Antígeno CD56/imunologia , Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Imunoconjugados/administração & dosagem , Neoplasias Pulmonares/patologia , Masculino , Maitansina/administração & dosagem , Maitansina/análogos & derivados , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida
12.
Clin Lung Cancer ; 18(3): 259-273.e8, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28162945

RESUMO

The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016. All phase III randomized controlled trials (RCTs) and relevant systematic reviews were included. Data on overall survival (OS), disease-free survival, adverse events, and quality of life were extracted from each of the studies. Two relevant systematic reviews, 13 RCTs, and a series of pooled analyses by Lung Adjuvant Cisplatin Evaluation-Biomarker were included in the present review. Adjuvant chemotherapy statistically significantly improved OS for resected stage II-IIIA NSCLC and is recommended. For patients with stage IB NSCLC, no significant improvement was seen in OS; however, the results from subgroup analyses indicate that it would be reasonable to consider adjuvant chemotherapy for patients with larger tumors (≥ 4 cm). The present data do not support the use of adjuvant novel therapies (ie, epidermal growth factor receptor tyrosine kinase inhibitor, bevacizumab, and immunotherapy) either as an addition to, or instead of, cytotoxic chemotherapy. No predictive biomarkers are available to select patients more likely to benefit from adjuvant chemotherapy. Cytotoxic chemotherapy remains the standard of care as adjuvant therapy for patients with resected stage II-IIIA NSCLC. Additional clinical trials are needed to evaluate targeted agents in molecularly defined subgroups before these agents can be recommended in the adjuvant setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias Pulmonares/tratamento farmacológico , Pneumonectomia , Complicações Pós-Operatórias/prevenção & controle , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Morte Celular , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
13.
Clin Lung Cancer ; 18(2): 105-121.e5, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27908621

RESUMO

Patients with early-stage non-small-cell lung cancer (NSCLC) who are unable to undergo surgery can be offered radiation therapy (RT). Previously, conventional RT was offered; however, newer techniques such as stereotactic body RT (SBRT) have become available. The objective of the present systematic review was to investigate the effectiveness of RT with curative intent in patients with early-stage medically inoperable NSCLC. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing stereotactic RT with curative intent compared with observation or other types of RT for early-stage, medically inoperable, NSCLC. Comparisons of radiation dosing or fractionation schedules for SBRT were included. We include 4 systematic reviews and 52 observational studies. The evidence suggests that SBRT compared with observation or other forms of RT, such as accelerated hypofractionated RT, 3-dimensional conformal RT, conventional fractionated RT, external beam RT, proton beam therapy, and carbon ion therapy, could have similar or improved results in survival or local control, with similar or fewer adverse effects. Evidence also suggests that local tumor control and survival were associated with the biologically effective dose (BED) for SBRT. Several studies suggested a cutoff of approximately 100 BED correlated significantly with patient outcomes. The presented evidence suggests that SBRT compared with other forms of RT is a reasonable treatment option for patients with medically inoperable early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Prognóstico
14.
Lung Cancer ; 99: 180-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27565937

RESUMO

In stage III non-small cell lung cancer (NSCLC), the standard of care in young patients is chemoradiotherapy, but this standard is not as clearly established for older patients. We aimed to determine the efficacy and harm associated with chemoradiotherapy versus radiotherapy alone in elderly (≥70 years), stage III NSCLC patients through a systematic review. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and conference proceedings. Two reviewers independently identified randomized trials (RCT) and extracted trial-level data. Risk of bias was assessed and meta-analysis was conducted looking at survival and safety outcomes. We included three trials and subgroup data from one systematic review. The three RCTs had high risk of bias due primarily to lack of blinding and the systematic review scored 4/11 using the AMSTAR tool. Overall survival (HR 0.66, 95% CI 0.53-0.82; I2 0%; 3 trials; 407 patients) and progression-free survival (HR 0.67, 95% CI 0.53-0.85; I2 0%; 2 trials; 327 patients) both favored chemoradiotherapy. Risk of treatment-related death and grade 3+ pneumonitis were not significantly different between groups. In conclusion, treatment of stage III NSCLC patients 70 years or older with chemotherapy and radiotherapy is associated with improved overall survival compared to radiotherapy alone. With the exception of increased hematological toxicity, CRT appears to be tolerable in fit elderly patients and represents a reasonable standard of clinical care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Radioterapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Humanos , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Radioterapia/efeitos adversos , Radioterapia/métodos , Resultado do Tratamento
15.
Drugs ; 76(14): 1321-36, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27557830

RESUMO

Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum-based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10-15 years have established pemetrexed (non-squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements. Trials comparing these agents with other chemotherapy, evaluating the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to chemotherapy or the addition of another targeted agent to erlotinib or gefitinib have all failed to demonstrate an improvement in overall survival for patients with NSCLC. In contrast, recent data comparing therapy with novel monoclonal antibodies against programmed cell death 1 (PD-1) or PD ligand (PD-L1) pathway versus standard chemotherapy following platinum failure have demonstrated significant improvements in overall survival. Therapy with nivolumab or pembrolizumab would now be considered standard second-line therapy in patients without contraindication to immune checkpoint inhibitors. Atezolizumab also appears promising in this setting.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação/genética , Oncogenes/genética
16.
Clin Lung Cancer ; 17(6): 563-572.e2, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27374398

RESUMO

BACKGROUND: Physiologic changes of aging in combination with greater comorbidity could lead to treatment nihilism for elderly patients (≥ 70 years old) with non-small-cell lung cancer (NSCLC). Randomized trials have shown improved survival with chemotherapy since 1999, but it remains unclear whether these data have translated into practice. PATIENTS AND METHODS: We conducted a retrospective, population-based cohort study of NSCLC cases diagnosed in Ontario, Canada from 2000 to 2010. We compared referral and treatment patterns among patients aged < 70 versus ≥ 70 years. Multivariable analyses evaluated predictors of referral to medical oncology or treatment with chemotherapy. RESULTS: Of 61,646 patients with NSCLC, 32,131 (52.1%) were ≥ 70 years. Fewer adenocarcinomas were diagnosed in the elderly (29.8% vs. 44%), and more elderly patients lacked microscopic confirmation of malignancy (20.1% vs. 6.2%). Charlson co-morbidity scores ≥ 2 (14.0% vs. 7.4%) were higher in the elderly. Only 59.5% of elderly patients with NSCLC were referred to a medical oncologist, versus 78.5% of younger patients. Elderly patients were less likely to receive chemotherapy (18.3% vs. 46.7%), even among those referred to a medical oncologist (30.1% vs. 58.6%). Neither referral nor treatment changed substantially over time. The elderly also had a shorter median survival (5.8 vs. 9.6 months); however, there was less difference in median survival (13.6 vs. 14.9 months) among patients receiving chemotherapy. CONCLUSION: Elderly patients are less likely to be considered for systemic therapy for NSCLC, and evidence of benefit has had minimal impact on practice. We believe this disparity could be improved through systematically using tools to comprehensively assess elderly patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Padrões de Prática Médica , Encaminhamento e Consulta , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
J Thorac Oncol ; 11(7): 989-1002, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27013406

RESUMO

INTRODUCTION: Non-small cell lung cancer (NSCLC) is often diagnosed at later stages when treatment options are limited. Maintenance therapy may prolong the time to disease progression and potentially increase overall survival. Secondarily, it may increase the proportion of patients eligible for second-line therapy at the time of progression. The objective of this systematic review was to examine the use of systemic treatment in the maintenance of patients with NSCLC. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched for phase III randomized controlled trials comparing maintenance systemic treatment against another systemic treatment or placebo in patients with stage IIIB or IV NSCLC who had received a minimum of four prior cycles of platinum-based chemotherapy. Meta-analyses were conducted with clinically homogenous trials. RESULTS: Fourteen randomized controlled trials with 22 publications were included. The overall survival benefit was strongest for maintenance therapy with pemetrexed for patients with nonsquamous NSCLC (hazard ratio = 0.74, 95% confidence interval: 0.64-0.86) but not significant for patients with squamous NSCLC. There was also an overall survival benefit with maintenance therapy with epidermal growth factor receptor tyrosine kinase inhibitors, but the magnitude of the benefit was smaller than with pemetrexed (hazard ratio = 0.84, 95% confidence interval: 0.75-0.94). Docetaxel or gemcitabine as maintenance chemotherapies did not have an impact on overall survival. CONCLUSION: For patients with advanced, stable stage IIIB/IV NSCLC whose disease has not progressed after four to six cycles of platinum-based chemotherapy, the overall survival benefits were strongest for pemetrexed maintenance therapy followed by epidermal growth factor receptor tyrosine kinase inhibitor maintenance therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pemetrexede/uso terapêutico , Taxoides/uso terapêutico
18.
Br J Cancer ; 114(6): 616-22, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26889973

RESUMO

BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association. RESULTS: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02). CONCLUSIONS: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade
19.
J Thorac Oncol ; 11(3): 312-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26749487

RESUMO

OBJECTIVES: This pooled analysis of four trials of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) versus placebo was conducted to clarify the prognostic and predictive roles of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (MUTs) and to explore the importance of MUT subtype. METHODS: Data were pooled from four trials of EGFR TKIs versus placebo (National Cancer Institute of Canada Clinical Trials Group [NCIC CTG] trial BR.21, TOPICAL, NCIC CTG trial BR.26, and NCIC CTG trial BR.19). Analyses of the combined data were performed to determine relationships of MUT status/subtype to response and survival end points. RESULTS: KRAS status was known for 1362 of 2624 patients (785 receiving EGFR TKIs and 577 receiving placebo); 275 (20%) had KRAS MUTs (248 at codon 12; 15 at codon 13; 12 at other codons). In the placebo arms there was no difference in overall survival (OS) for patients with KRAS MUTs or wild-type tumors (hazard ratio [HR] = 1.04, confidence interval [CI]: 0.81-1.33 for univariable analysis and HR = 1.09, CI: 0.85-1.41 for multivariable analysis). Patients with guanine-to-thymidine transversion MUTs had longer OS than did those with guanine-to-adenine transition MUTs or guanine-to-cytosine transversion MUTs (median OS 6.3, 1.8, and 3.9 months, respectively, p = 0.01). Patients with KRAS MUT tumors derived no benefit from EGFR TKIs (OS HR = 1.13, CI: 0.85-1.51; progression-free survival HR = 1.02, CI: 0.76-1.36). The interaction between KRAS status and EGFR TKI effect was significant for progression-free survival (p = 0.04) but not for OS (p = 0.17). For patients with G12V MUTs, EGFR TKI treatment was harmful (OS HR = 1.96, CI: 1.03-3.70, p = 0.04), whereas guanine-to-adenine transition MUTs were associated with an OS benefit from EGFR TKIs (HR = 0.49, CI: 0.24-1.00, p = 0.05). CONCLUSIONS: Overall, KRAS MUT is neither prognostic nor predictive of benefit from EGFR TKIs. However, it appears that KRAS MUT subtypes are not homogeneous in terms of their prognostic and predictive effects. These observations require prospective validation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Adv Exp Med Biol ; 893: 91-126, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26667340

RESUMO

Upregulation of angiogenesis is a frequent occurrence in lung cancer and is reported to represent a negative prognostic factor. This provides a rationale for the development and evaluation of anti-angiogenic agents. To date bevacizumab, a monoclonal antibody directed against serum VEGF, is the only anti-angiogenic agent that has demonstrated improved overall survival for patients with lung cancer. Meta-analysis of trials of bevacizumab in combination with platinum-based chemotherapy for NSCLC, show a 10% reduction in the risk of death (HR 0.90, 95% CI 0.81-0.99). However, therapy with bevacizumab is limited to NSCLC patients with non-squamous histology, good performance status, no brain metastases and the absence of bleeding or thrombotic disorders. More recently, similar survival was observed in a non bevacizumab containing regimen of carboplatin, pemetrexed and maintenance pemetrexed. Multiple oral anti-angiogenic compounds have been evaluated in NSCLC, both in first-line therapy, or upon disease progression. The majority of agents have shown some evidence of activity, but none have clearly demonstrated improvements in overall survival. Increased toxicities have been observed, including an increased risk of death for some agents, limiting their development. Promising data exist for sunitinib in patients with heavily pre-treated NSCLC, and nintedanib in combination with docetaxel, as second-line therapy for NSCLC. However, these findings require validation. Currently, there is no established role for anti-angiogenic therapy in SCLC, although there is some promise for sunitinib as maintenance therapy following platinum and etoposide chemotherapy. The challenge for anti-angiogenic therapy is to understand whether treatment effects in a subpopulation, are lost among a larger unselected population of patients. There is a need for additional translational research to identify predictive biomarkers for anti-angiogenic therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Medicina de Precisão , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA