Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy

Background/Aim. First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. Patients and methods. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Results. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Conclusion. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors (AU)

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Relación entre el índice de Breslow y el resultado de la PET-TC en la estadificación inicial del melanoma cutáneo: ¿es posible establecer un punto de corte? / Breslow thickness and 18F-FDG PET-CT result in initial staging of cutaneous melanoma: Can a cut-off point be established?

Objetivo. Establecer un punto de corte del índice de Breslow (IB) para la indicación del estudio PET-TC en la estadificación del melanoma cutáneo en estadios iniciales y evaluar su valor pronóstico. Material y métodos. Análisis retrospectivo de 347 estudios PET-TC con 18F-FDG con diagnóstico de melanoma, siendo 108 de estadificación. Excluimos 31 obteniendo una muestra final de 77 pacientes. Para establecer el punto de corte óptimo llevamos a cabo un análisis de la curva ROC. Para evaluar el valor pronóstico se realizó un análisis de supervivencia registrando la muerte atribuible al melanoma. Resultados. De los 77 pacientes, 47 eran varones (61,04%) y 11 (14,29%) presentaron un resultado PET-TC positivo. La edad media fue 65,17 ± 15,00 años. La mediana del IB en el grupo con PET-TC negativo fue 2,75 mm (IQR 1,83-4,50) y en el grupo con resultado positivo 6,25 mm (IQR 5,40-7,50) (p = 0,0013). El análisis de la curva ROC (AUC 0,804, SE 0,054) dio como óptimo un punto de corte de 5 mm: sensibilidad 90,91%, especificidad 78,79%, VPN 98,1%, VPP 41,7%, OR diagnóstica 37,1 y exactitud diagnóstica 80,52%. El seguimiento medio fue de 18,66 ± 14,35 meses, observándose 3,77% muertes en el grupo con IB < 5 mm y 29,17% en el grupo con IB ≥ 5 mm. Las curvas de supervivencia entre ambos grupos fueron significativamente diferentes (p = 0,0013). Conclusiones. Un punto de corte de IB de 5 mm discrimina de manera adecuada a aquellos pacientes con PET-TC positiva de aquellos con resultado negativo en estadios precoces del melanoma cutáneo, por lo que podría incluirse en la estadificación inicial de este subgrupo de pacientes (AU)

Aim. To establish a Breslow Thickness (BT) cut-off point for indication of PET-CT of cutaneous melanoma in early stages and evaluate its prognostic value. Material and methods. Retrospective analysis of 347 PET-CT studies with diagnosis of melanoma, of which 108 were performed for initial staging. Thirty-one patients were excluded, and a final sample of 77 patients remained. A ROC curve analysis was performed to establish an optimal cut-off point. A survival analysis was performed, considering death assignable to melanoma as the main event, for the evaluation of its prognostic value. Results. Forty-seven (61.04%) of all 77 patients selected were men, and 11 (14.29%) had a positive PET-CT result. Mean age was 65.17 ± 15.00 years. The median BT in patients with a negative PET-CT result was 2.75 mm (IQR 1.83-4.50) and in the positive group 6.25 mm (IQR 5.40-7.50) (P=.0013). In the ROC curve analysis (AUC 0.804, SE 0.054), an optimal value of 5 mm BT with the following values was obtained: sensitivity 90.91%, specificity 78.79%, negative predictive value (NPV) 98.1%, positive predictive value (PPV) 41.7%, diagnostic OR 37.1, and accuracy 80.52%. Mean follow-up was 18.66 ± 14,35 months, detecting 2/53 (3.77%) deaths in the BT < 5 mm group, and 7/24 (29.17%) in the BT≥5 mm group. Survival curves between both groups were significantly different (P=.0013). Conclusions. A 5 mm cut-off point correctly distinguishes those patients with positive PET-CT from those with negative results in the early stages of cutaneous melanoma; therefore it could be included in initial staging of this subgroup of patients (AU)

A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer

Purpose: To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). Methods/patients: Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. Results: Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency. Conclusions: Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies (AU)

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Cost-effectiveness evaluation of sunitinib as first-line targeted therapy for metastatic renal cell carcinoma in Spain

INTRODUCTION Sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, delays disease progression, with a median overall survival (OS) of more than 2 years, improves quality of life and is becoming the first-line standard of care for metastatic renal carcinoma (mRCC). PURPOSE To assess the economic value of sunitinib as fi rst-line therapy in mRCC within the Spanish healthcare system. METHODS An adapted Markov model with a 10-year time horizon was used to analyse the cost effectiveness of sunitinib vs. sorafenib (SFN) and bevacizumab/interferon-α (BEV/IFN) as first-line mRCC therapy from the Spanish third-party payer perspective. Progression-free survival (PFS) and OS data from sunitinib, SFN and BEV/IFN pivotal trials were extrapolated to project survival and costs in 6-week cycles. Results, in progression-free life-years (PFLY), life years (LY) and quality-adjusted life-years (QALY) gained, expressed as incremental cost-effectiveness ratios (ICER) with costs and benefits discounted annually at 3%, were obtained using deterministic and probabilistic analyses. RESULTS Sunitinib was more effective and less costly than both SFN (gains of 0.52 PFLY, 0.16 LY, 0.17 QALY) and BEV/IFN (gains of 0.19 PFLY, 0.23 LY, 0.16 QALY) with average cost savings/patients of €1,124 and €23,218, respectively. Using a willingness-to-pay (WTP) threshold of €50,000/QALY, sunitinib achieved an incremental net benefit (INB) of €9,717 and €31,211 compared with SFN and BEV/IFN, respectively. At this WTP, the probability of sunitinib providing the highest INB was 75%. CONCLUSION Our analysis suggests that sunitinib is a costeffective alternative to other targeted therapies as first-line mRCC therapy in the Spanish healthcare setting (AU)

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04)

BACKGROUND: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. MATERIALS AND METHODS: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. RESULTS: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. CONCLUSIONS: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival (AU)