Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the Thoracic Tumor Registry.

BACKGROUND: Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce. PATIENTS AND METHODS: This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. RESULTS: With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8-10.2 months), with an estimated rate of 70.3% (95% CI 67.2-73.4%), 38.9% (95% CI 35.4-42.4%), and 14.8% (95% CI 11.8-17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1-2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. CONCLUSION: This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.

ASTRIS, a large real-world study to evaluate the efficacy of osimertinib in epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer patients: Clinical characteristics and genotyping methods in a Spanish cohort / ASTRIS, un gran estudio en el mundo real para evaluar la eficacia de osimertinib en pacientes de cáncer de pulmón no microcítico positivo a la mutación de T790M del receptor del factor de crecimiento epidérmico: características clínicas y métodos de genotipificación en una cohorte española

PURPOSE: Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. METHODS: ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. RESULTS: The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. CONCLUSIONS: ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices

OBJETIVO: Osimertinib ha probado su eficacia en los pacientes de cáncer de pulmón no microcítico (CPNM) positivo a la mutación de EGFR T790M; sin embargo, sus beneficios no han sido evaluados en el mundo real. MÉTODOS: ASTRIS es un estudio de brazo único, abierto y multinacional para evaluar la eficacia y la seguridad de osimertinib para el tratamiento del CPNM positivo a la mutación de EGFR T790M. Presentamos el diseño del estudio y los resultados del análisis del punto de corte (octubre de 2017), que describe las características basales y la metodología de la detección de la mutación de T790M en la cohorte española. RESULTADOS: La cohorte española incluyó 131 pacientes de entre un total de 3.014 sujetos. Cuarenta pacientes (28,1%) seguían en terapia en el momento del punto de corte, el 68,7% eran mujeres y el 97,7% eran caucásicos, con una edad media de 64,8 (DE: 11,7) años. El tipo más común de muestra para evaluar las mutaciones de T790M fue tisular (55%), habiéndose obtenido las muestras del tumor primario en el 61,1% de los casos. El análisis de la mutación fue realizado por parte del laboratorio local en el 60,3% de los casos, utilizando el ensayo Roche Cobas® EGFR en el 43,5% de los casos. CONCLUSIONES: Se espera que ASTRIS confirme los beneficios de osimertinib en el mundo real. Los datos sobre las prácticas en el mundo real para la detección de la mutación de EGFR T790M podrían proporcionar información adicional para aportar directrices sobre las mejores prácticas

ASTRIS, a large real-world study to evaluate the efficacy of osimertinib in epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer patients: Clinical characteristics and genotyping methods in a Spanish cohort.

PURPOSE: Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. METHODS: ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. RESULTS: The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. CONCLUSIONS: ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices.

Experience in the use of sunitinib given as a single agent in metastatic chemoresistant and castration-resistant prostate cancer patients.

OBJECTIVE: Vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) correlate with poor prognosis in castration-resistant prostate cancer (CRPC). Sunitinib has shown activity in CRPC and at the time of this analysis there was no standard therapy for docetaxel-refractory CRPC. METHODS: We present a case series data collection of 19 patients with a median age of 73 years, CRPC and rising prostate-specific antigen (PSA). Patients received sunitinib 37.5 mg continuous daily dose. One cycle comprised a 4-week period. Patients were evaluated by CT scan every 8 weeks and PSA was monitored every 4 weeks. RESULTS: Median Eastern Cooperative Oncology Group (ECOG) performance status score was 2. Patients received a median of two previous treatment lines for the hormone-refractory setting. Baseline median PSA was 280 ng/ml. Patients received a median of 16 weeks of therapy (4 - 48+). One patient achieved a partial response (5%) and 12 (66.7%) achieved stable disease for at least 3 months according to RECIST criteria. Median progression-free survival was 4 months. PSA declined > 50% in 5/19 (26.3%) and stabilized in 7/19 (37%) patients. Frequent adverse events were grade 3 asthenia (21%), grade 3 diarrhea (10%) and grade 3 hand-foot syndrome (15.7%). CONCLUSIONS: Activity with sunitinib was observed in highly pretreated docetaxel-refractory CRPC with acceptable tolerability. Additional studies should confirm the role of antiangiogenic agents in this setting.

Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine.

BACKGROUND: New chemotherapeutic agents, including paclitaxel and gemcitabine, are active in advanced bladder carcinoma, and combination regimens with these agents have shown promising results. Unlike conventional chemotherapy regimens, such as methotrexate, vinblastine, doxorubicin, and cisplatin, there are no data available on key predictive factors for response and survival with these novel agents. Since this information is needed for selection of patients for these new combinations and for stratification purposes in ongoing randomized trials, the authors aimed to study the predictive factors for response and survival to the current regimen containing cisplatin, paclitaxel, and gemcitabine. METHODS: The authors studied 56 patients with advanced urothelial tumors treated on a Phase I/II trial of paclitaxel, cisplatin, and gemcitabine (TCG) to identify pretreatment characteristics that were prognostic for survival using this novel combination. The pretreatment characteristics analyzed were age, gender, Eastern Cooperative Oncology Group performance status, histopathology (pure transitional versus other), visceral (liver, lung, or bone) metastasis, number of sites of disease, lactate dehydrogenase, and hemoglobin. RESULTS: The factors that were associated with a worse survival in univariate analysis were performance status > 0, presence of visceral metastasis, and more than one site of malignant disease. In a multivariate model, performance status (P = 0.044) and visceral disease (P = 0.008) showed independent statistical significance for decreased survival. Patients were then grouped based on these two independent prognostic factors. Median survival times in the groups of patients with zero, one, or two of these risk factors were 32.8 months, 17 months, and 9.6 months, respectively (P = 0.0005). CONCLUSIONS: A pretreatment performance status > 0 and the presence of visceral metastasis have a profound impact on survival when using the TCG regimen. These two variables will be used to stratify patients in the upcoming Phase III randomized trial comparing this TGC regimen with a gemcitabine/cisplatin regimen in advanced urothelial tumors.