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PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden – fatigue (p = 0.03), pain (p

Background The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co‐occurring mutations of non‐small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). Methods This was a retrospective cross‐sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma. Results We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P, This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling.

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Introduction We analyzed the prevalence of non–small-cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 50% and compared the results with the existing data from clinical trials and databases from other countries. Materials and Methods The Latin American Cooperative Oncology Group and Grupo Brasileiro de Oncologia Toracica performed a retrospective, cross-sectional study from August 2017 to April 2018. PD-L1 expression was collected from pathology reports from 5 laboratories in Brazil. All tests were sponsored by the pharmaceutical industry on request from the treating medical oncologist. PD-L1 expression was assessed by immunohistochemistry. The variables were summarized as absolute and relative frequencies or the median and interquartile range. Pearson's χ2 test was used to compare the TPS categories stratified by sex, age, and histologic type. All analyses were performed with SAS, version 9.4, and were deemed statistically significant at P Results A total of 1512 patients were included in the present study. Their median age was 66 years. Most patients were men (56.02%), and the most common histologic type was adenocarcinoma (58.04%); 109 tumors (11.31%) had EGFR mutations and 34 (3.64%) had ALK gene rearrangements. Overall, 56.54% had a PD-L1 TPS Conclusion The prevalence of high PD-L1 expression among the Brazilian NSCLC samples was lower than previously described in other countries, which could affect the number of patients who might be candidates for immunotherapy alone.

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum–etoposide) in treatment-naive patients with ES-SCLC. Methods: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; or platinum–etoposide alone. All drugs were administered intravenously. Platinum–etoposide consisted of etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL per min or cisplatin 75–80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum–etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum–etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum–etoposide group versus the platinum–etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum–etoposide group and 269 to the platinum–etoposide group. Durvalumab plus platinum–etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59–0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5–14·8) in the durvalumab plus platinum–etoposide group versus 10·3 months (9·3–11·2) in the platinum–etoposide group, with 34% (26·9–41·0) versus 25% (18·4–31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum–etoposide group and 166 (62%) of 266 in the platinum–etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation: First-line durvalumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Funding: AstraZeneca.

Objective Pemetrexed plus carboplatin offers survival advantage in first line treatment of advanced lung cancer patients with performance status of 2. We estimated the cost-effectiveness of this combined regimen compared to pemetrexed alone in a Brazilian population. Methods A cost-effectiveness analysis was conducted based on a randomized phase III trial in patients with advanced non-small cell lung cancer (NSCLC) and ECOG performance status of 2 (PS2), comparing doublet regimen pemetrexed plus carboplatin with pemetrexed alone. The perspective adopted was the public health care sector over a three-year period. Direct medical costs and survival time were calculated from patient-level data and utility values were extracted from the literature. Sensitivity analyses were performed to evaluate uncertainties in the results. Results and conclusion The combined regimen pemetrexed plus carboplatin yielded a gain of 0.16 life year (LY) and 0.12 quality-adjusted life year (QALY) compared to pemetrexed alone. The total cost was 17,674.31 USD for the combined regimen and 15,722.39 USD for pemetrexed alone. The incremental cost-effectiveness ratio (ICER) was $12,016.09 per LY gained and $15,732.05 per QALY gained. The factors with the greatest impact on the ICER are pemetrexed price and the time to progression utility value. The cost-effectiveness acceptability curve showed an upper 90% probability of pemetrexed plus carboplatin being cost-effective with a threshold between two and three GDP per capita. Our study suggests superiority of the combined pemetrexed plus carboplatin regimen in terms of efficacy as well as cost-effectiveness in advanced NSCLC patients with a poor performance status of 2.

Background Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START. Patients and methods START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type. Results Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77–1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68–0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed. Conclusion Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit. ClinicalTrials.gov number NCT00409188.

Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer. RESUMO O câncer de pulmão é um dos tipos de câncer com maior incidência e uma das principais causas de mortalidade por câncer no Brasil. Revisamos a situação atual do câncer de pulmão por meio de pesquisa de dados relevantes a respeito de prevenção, diagnóstico e tratamento no país. Esta revisão mostra várias questões que precisam de atenção, tais como controle do tabagismo, educação dos pacientes, desconhecimento por parte dos pacientes, diagnóstico tardio e desigualdade de acesso ao tratamento de câncer no Brasil. Propomos estratégias para ajudar a superar essas limitações e desafiamos os profissionais de saúde, a sociedade e os representantes do governo a trabalhar em conjunto e dar um passo à frente na luta contra o câncer de pulmão.

e18311 Background: Oral antineoplastic therapy is a growing reality, and ensures greater comfort and better quality of life for patients. However, this modality of treatment requires greater attention of the professionals to avoid dispensing errors and to guarantee adherence to the treatment. The goal of this study is to present a method to follow up cancer patients to reduce percentage of problems related to medication and improve oral antineoplastic adherence. Methods: The study was conducted at a private oncology clinic in Rio de Janeiro during the year 2018. In the first dispensation, patients received verbal and written pharmaceutical advice on posology, proper storage, safe handling requirements and strategies to avoid adverse side effects and food and drugs interactions. There were also given nutrition, sexuality, rights and duties guidelines. To improve adherence and to avoid forgetfulness or duplicity of dosing, patients received a medication calendar. Pharmacist made dispensing, managed adverse side effects and assessed adherence of patient using a model based on Morisky Medication Adherence Scale. Patients that answered "yes" to any questions were considered non-adherents. All information was registered in medical record. Non-compliances were considered: wrong medicine, incorrect dose and delays of any administrative reason. Results: In 2018, on average 1487 dispensings were made and 1053 patients’ adherence behavior were measured. 94.37% were considered adherent. Monthly percentage of non-compliance was 1.5% of dispensings. Conclusions: The present study demonstrates that with education and pharmaceutical follow-up since the first dispensation, it is possible to guarantee a safer and more effective treatment for patients using oral cancer medication. It is imperative to maintain the objective of developing better techniques for dispensing, guiding and guaranteeing high adherence.

Purpose To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. Patients and Methods In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m2) or CP (area under the curve of 5 and 500 mg/m2, respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS). Results A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm. Conclusion Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

SummaryTwo classes of epidermal growth factor receptor (EGFR) inhibitors are currently available for clinical use: tyrosine-kinase inhibitors (TKIs) and monoclonal antibodies. The introduction of pharmacological agents that are able to inhibit EGFR represents an important step in the management of patients with advanced non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide. The use of EGFR inhibitors has not only led to meaningful therapeutic gains for patients, but has also expanded our knowledge about the disease itself, as it is now recognized that activating mutations of EGFR play a pathogenetic role in NSCLC, especially in adenocarcinoma, patients who never smoked or former light smokers, females, and Asian individuals. Patients with NSCLC and one or more of these features are more likely to harbor tumors with EGFR mutations, and hence to respond to TKIs, than individuals without these features. Currently, TKIs are considered by many as the treatment of first choice in both the first- and second-line treatment of patients with clinical or molecular predictors of therapeutic benefit, and chemotherapy is a second option in these cases, especially when activating mutations of EGFR are present. Moreover, TKIs and anti- EGFR antibodies may be used in other settings, and their therapeutic role in NSCLC is clearly expanding. However, despite an initially successful treatment course, patients with advanced NSCLC eventually develop resistance to TKIs; and novel agents that hold promise for the future include irreversible EGFR inhibitors with activity against resistance-conferring EGFR mutations.

e21140Background: Immune checkpoint inhibitors improved outcomes of patients with advanced non-small cell lung cancer (NSCLC). KEYNOTE-024 trial demonstrated that immunotherapy was superior to plat...

INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival of patients with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. RESULTS: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages. INTRODUÇÃO: Dados de desfechos em câncer de pulmão de células não pequenas (CPCNP) são escassos no contexto da saúde suplementar no Brasil. O objetivo deste estudo foi descrever as características, tratamentos realizados e a sobrevida desses pacientes em uma instituição oncológica privada brasileira. MÉTODOS: Foram revisados os prontuários de pacientes atendidos entre 1998 e 2010 com diagnóstico de CPCNP. Os dados foram transferidos para uma ficha clínica individual e posteriormente analisados. Pacientes ou familiares foram contatados a fim de otimizar o seguimento e a estimativa da sobrevida. RESULTADOS: Foram incluídos 566 pacientes, com idade mediana de 65 anos. Predominaram os diagnósticos em estádios avançados (79,6% III/IV). A sobrevida mediana foi de 19,0 meses (IC95% 16,2 - 21,8), sendo de 99,7, 32,5, 20,2 e de 13,3 meses nos estádios I, II, III e IV, respectivamente (p < 0,0001). Entre os pacientes que receberam quimioterapia paliativa, a sobrevida mediana foi de 12,2 meses (IC95% 10,0 - 14.4). CONCLUSÕES: Os desfechos encontrados se assemelham aos de países desenvolvidos. Apesar do maior acesso médico em pacientes com cobertura de planos de saúde, a maioria dos diagnósticos ocorre tardiamente.

e20611Background: Lung adenocarcinoma in never-smokers (LANS) is a disease largely defined by targetable oncogenic mutations. High frequency of actionable genomic alterations has been reported in c...

OBJETIVO: A quimioterapia adjuvante é recomendada na maioria dos casos de câncer de pulmão de células não pequenas (CPCNP) ressecados em pacientes nos estádios II ou IIIA. No entanto, diferentes esquemas quimioterápicos contendo cisplatina foram utilizados em estudos de fase III, e a melhor escolha permanece obscura. O objetivo deste estudo foi descrever a experiência do Instituto Nacional de Câncer (INCA), localizado na cidade do Rio de Janeiro (RJ), com o uso da combinação de cisplatina e etoposídeo nessa situação, com especial foco para os dados de sobrevida. MÉTODOS: Foram avaliados retrospectivamente os prontuários dos pacientes com diagnóstico de CPCNP que receberam terapia adjuvante no INCA entre 2004 e 2008. RESULTADOS: Foram incluídos 51 pacientes, e todos foram tratados com a combinação de cisplatina e etoposídeo. A mediana de tempo de seguimento foi de 31 meses de seguimento, e a mediana de sobrevida global foi de 57 meses. Na análise univariada, a sobrevida foi inferior nos pacientes submetidos a radioterapia + quimioterapia do que aqueles somente submetidos a quimioterapia (mediana de 19 vs. 57 meses; p < 0,001), e houve uma tendência a menor sobrevida nos pacientes em estádio III em relação àqueles em estádios I-II (mediana de 34 vs. 57 meses, respectivamente; p = 0,22). Não houve associações significativas entre a sobrevida global e gênero (p = 0,70), padrão histológico (p = 0,33) ou dose de cisplatina (p = 0,13). CONCLUSÕES: Nossos resultados corroboram a utilização da quimioterapia adjuvante, e os resultados de sobrevida se aproximam daqueles descritos nos principais ensaios clínicos randomizados. Contudo, é importante o acompanhamento a longo prazo nessa população OBJECTIVE: Adjuvant chemotherapy is recommended for most patients submitted to resection due to non-small cell lung cancer (NSCLC) staged as II or IIIA. However, although various chemotherapy regimens that include cisplatin have been used in phase III trials, the best choice remains unclear. The objective of this study was to describe the experience of the Instituto Nacional do Câncer (INCA, Brazilian National Cancer Institute), located in the city of Rio de Janeiro, Brazil, with the use of the cisplatin-etoposide combination in such patients, with a special focus on survival data. METHODS: We retrospectively evaluated the medical charts of the patients receiving adjuvant therapy for NSCLC at the INCA between 2004 and 2008. RESULTS: We included 51 patients, all of whom were treated with the cisplatin-etoposide combination. The median follow-up period was 31 months, and the median overall survival was 57 months. In the univariate analysis, median survival was lower in the patients submitted to chemotherapy plus radiotherapy than in those submitted to chemotherapy alone (19 vs. 57 months; p < 0.001), and there was a trend toward lower median survival in stage III patients than in stage I-II patients (34 vs. 57 months; p = 0.22). Overall survival was not significantly associated with gender (p = 0.70), histological pattern (p = 0.33), or cisplatin dose (p = 0.13). CONCLUSIONS: Our results support the use of adjuvant chemotherapy, and our survival data are similar to those reported in major randomized clinical trials. However, long-term follow-up is warranted in this population

Adjuvant chemotherapy is recommended for most patients submitted to resection due to non-small cell lung cancer (NSCLC) staged as II or IIIA. However, although various chemotherapy regimens that include cisplatin have been used in phase III trials, the best choice remains unclear. The objective of this study was to describe the experience of the Instituto Nacional do Câncer (INCA, Brazilian National Cancer Institute), located in the city of Rio de Janeiro, Brazil, with the use of the cisplatin-etoposide combination in such patients, with a special focus on survival data.We retrospectively evaluated the medical charts of the patients receiving adjuvant therapy for NSCLC at the INCA between 2004 and 2008.We included 51 patients, all of whom were treated with the cisplatin-etoposide combination. The median follow-up period was 31 months, and the median overall survival was 57 months. In the univariate analysis, median survival was lower in the patients submitted to chemotherapy plus radiotherapy than in those submitted to chemotherapy alone (19 vs. 57 months; p0.001), and there was a trend toward lower median survival in stage III patients than in stage I-II patients (34 vs. 57 months; p = 0.22). Overall survival was not significantly associated with gender (p = 0.70), histological pattern (p = 0.33), or cisplatin dose (p = 0.13).Our results support the use of adjuvant chemotherapy, and our survival data are similar to those reported in major randomized clinical trials. However, long-term follow-up is warranted in this population.

Purpose This phase II/III double-blind study assessed efficacy and safety of cediranib with standard chemotherapy as initial therapy for advanced non–small-cell lung cancer (NSCLC). Patients and Methods Paclitaxel (200 mg/m2) and carboplatin (area under the serum concentration-time curve 6) were given every 3 weeks, with daily oral cediranib or placebo at 30 mg (first 45 patients received 45 mg). Progression-free survival (PFS) was the primary outcome of the phase II interim analysis; phase III would proceed if the hazard ratio (HR) for PFS ≤ 0.77 and toxicity were acceptable. Results A total of 296 patients were enrolled, 251 to the 30-mg cohort. The phase II interim analysis demonstrated a significantly higher response rate (RR) for cediranib than for placebo, HR of 0.77 for PFS, no excess hemoptysis, and a similar number of deaths in each arm. The study was halted to review imbalances in assigned causes of death. In the primary phase II analysis (30-mg cohort), the adjusted HR for PFS was 0.77 (95% CI, 0.56 to 1.08) with a higher RR for cediranib than for placebo (38% v 16%; P < .0001). Cediranib patients had more hypertension, hypothyroidism, hand-foot syndrome, and GI toxicity. Hypoalbuminemia, age ≥ 65 years, and female sex predicted increased toxicity. Survival update (N = 296) 10 months after study unblinding favored cediranib over placebo (median of 10.5 months v 10.1 months; HR, 0.78; 95% CI, 0.57 to 1.06; P = .11). Causes of death in the cediranib 30-mg cohort were NSCLC (81%), protocol toxicity ± NSCLC (13%), and other (6%); for the placebo group, they were 98%, 0%, and 2%, respectively. Conclusion The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS, but does not appear tolerable at a 30-mg dose. Consequently, the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a randomized, double-blind, placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC.

Purpose This report describes the quality of life (QOL) findings of a randomized placebo controlled study of erlotinib, an epidermal growth factor receptor inhibitor, in patients with non–small-cell lung cancer (NSCLC). Patients and Methods This double-blind phase III trial randomly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo, with survival as the primary study outcome. QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13. The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea, and pain. Results Survival was significantly longer (hazard ratio, 0.70; P < .0001) in the erlotinib arm. Compliance with QOL was 87% at baseline and more than 70% during treatment. Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms (4.9 v 3.7 months for cough [P = .04]; 4.7 v 2.9 months for dyspnea [P = .04], and 2.8 v 1.9 months for pain [P = .03]). QOL response analyses showed that 44%, 34%, and 42% of patients receiving erlotinib had improvement in these three symptoms, respectively. This was accompanied by a significant improvement in the physical function (31% erlotinib v 19% placebo, P = .01), and global QOL (35% v 26%, P < .0001). Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease (P < .01). Conclusion Erlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.

7506 Background: No standard of care exists for patients with advanced NSCLC and PS 2 and clinical practice ranges from supportive care to combination chemotherapy. Methods: In a Brazilian multicenter phase III randomized trial, advanced NSCLC patients, with any histology at first, amended to non-squamous only, PS 2, no prior chemotherapy, and adequate organ function, were randomized to P alone (500 mg/m2) or CP (AUC 5 + same P) administered every 3 weeks for 4 cycles. Stratification factors included stage (IIIB vs. IV); age (≥70 vs. nd line therapy Conclusions: Combination chemotherapy with CP significantly improves survival, with acceptable safety, in eligible patients with advanced NSCLC and PS 2, and represents a new standard.

7511 Background: In NCIC CTG study BR24, CED 30 mg/d + CP increased objective response rate (RR) and progression-free survival (PFS), but there were concerns regarding toxicity in some pts. BR29 tested a lower dose of CED 20 mg/d limiting accrual to pts without significant weight loss/hypoalbuminemia. Methods: Consenting, eligible adult pts with advanced incurable NSCLC of any histology were randomized to receive CED 20 mg/d or PLA with up to 6 cycles of C (AUC = 6) P (200 mg/m2); non-progressing pts continued CED/PLA after CP until progression, unacceptable toxicity or pt request. The primary endpoint was overall survival (OS). An interim analysis (IA) for PFS was planned after 170 events in the first 260 pts; the study would continue if the hazard ratio (HR) for PFS was < 0.7. Accrual continued until the required number of events was reached then held pending IA. Results: The trial was halted when the IA (n=260) revealed a HR for PFS of 0.89 (95% CI 0.66-1.20). A final analysis including all 306 randomized pts (median age 62, male 55%, PS 0 26%, PS 1 74%, adenocarcinoma 64%, squamous 13%, other histology 23%. RR was significantly higher with CED (52% vs 34 %, p = 0.001). For CED/PLA, respectively, median OS and PFS were 12.2/12.1 [HR: 0.95 (0.69-1.30, p=0.74)] and 5.5/5.5 months [HR: 0.91 (0.71-1.18, p=0.5)]. Grade >3 hypertension (15% vs 3%, p=0.0002), anorexia (7% vs 1%, p=0.02) and diarrhea (16% vs 1%, p