Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Multidisciplinary approach for locally advanced non-small cell lung cancer (NSCLC): 2023 expert consensus of the Spanish Lung Cancer Group GECP.

INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.

Expert consensus to optimize the management of older adult patients with advanced EGFR-mutated non-small cell lung cancer

Lung cancer (LC) is associated with ageing, with the average age of affected individuals being approximately 70 years. However, despite a higher incidence and prevalence among older people, the older adult population is underrepresented in clinical trials. For LC with Epidermal Growth Factor Receptor (EGFR) mutations, there is no clear association of this mutation with age. Geriatric assessments (GAs) and a multidisciplinary approach are essential for defining the optimal treatment. In this consensus, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sección de Oncogeriatría de la Sociedad Española de Oncología Médica—SEOM), the Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón—GECP) and the Association for Research on Lung Cancer in Women (Asociación para la Investigación del Cáncer de Pulmón en Mujeres—ICAPEM) evaluate the scientific evidence currently available and propose a series of recommendations to optimize the management of older adult patients with advanced LC with EGFR mutations (AU)

Expert consensus to optimize the management of older adult patients with advanced EGFR-mutated non-small cell lung cancer.

Lung cancer (LC) is associated with ageing, with the average age of affected individuals being approximately 70 years. However, despite a higher incidence and prevalence among older people, the older adult population is underrepresented in clinical trials. For LC with Epidermal Growth Factor Receptor (EGFR) mutations, there is no clear association of this mutation with age. Geriatric assessments (GAs) and a multidisciplinary approach are essential for defining the optimal treatment. In this consensus, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sección de Oncogeriatría de la Sociedad Española de Oncología Médica-SEOM), the Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón-GECP) and the Association for Research on Lung Cancer in Women (Asociación para la Investigación del Cáncer de Pulmón en Mujeres-ICAPEM) evaluate the scientific evidence currently available and propose a series of recommendations to optimize the management of older adult patients with advanced LC with EGFR mutations.

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study.

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy.

Efectividad y seguridad de atezolizumab, nivolumab y pembrolizumab en cáncer de pulmón no microcítico metastásico / Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer

Objetivo: Efectividad y seguridad de atezolizumab, nivolumab y pembrolizumab en cáncer de pulmón no microcítico metastásico.Método: Estudio observacional retrospectivo en pacientes con cáncer de pulmón no microcítico metastásico tratados en segunda línea oposteriores. La efectividad fue evaluada mediante supervivencia globaly supervivencia libre de progresión. La toxicidad mediante los CriteriosComunes de Terminología de Efectos Adversos v5.0.Resultados: Se incluyeron 8 pacientes con atezolizumab, 19 con nivolumab y 16 con pembrolizumab. La mediana de supervivencia libre deprogresión con atezolizumab fue 9,6 meses (intervalo de confianza del95% [IC95%] 2-17,2), 12,6 meses (IC95% 6,9-18,2) para nivolumab y8,5 meses (IC95% 0-19) para pembrolizumab. La mediana de supervivencia global con nivolumab fue 13,4 meses (IC95% 6-20,9) y no se alcanzópara atezolizumab y pembrolizumab. Ambas fueron superiores para lospacientes con 0-1 metástasis para nivolumab y en los pacientes conECOG 0-1 para pembrolizumab. Alrededor de un 85% de los pacientessufrieron efectos adversos. Dos pacientes tratados con nivolumab experimentaron vitíligo, con una supervivencia global mayor de 2,5 años.Conclusiones: En la muestra analizada, la efectividad de nivolumabes menor en pacientes con dos o más metástasis, y la de pembrolizumabes menor en pacientes con ECOG 2. La aparición de vitíligo se relacionócon una respuesta duradera. (AU)

Objective: To determine the effectiveness and safety of atezolizumab,nivolumab and pembrolizumab in patients with non-small cell lung cancer.Method: This is a retrospective observational study including patientstreated in second line and beyond. The effectiveness of treatment wasassessed by means of overall survival and progression free survival measurements. Toxicity was described according to the Common Criteria forAdverse Event Terminology v5.0.Results: The study included 8 patients treated with atezolizumab,19 withnivolumab, and 16 with pembrolizumab. Median progression free survival with atezolizumab was 9.6 months (95%CI 2-17.2), 12.6 months(95%CI 6.9-18.2) for nivolumab, and 8.5 months (95%CI 0-19) for pembrolizumab. Median overall survival was 13.4 months (95%CI 6-20.9)for nivolumab. Both PFS and OS were statistically higher in patients withgrade 0-1 metastasis in the case of nivolumab, and in ECOG 0-1 patientsfor pembrolizumab. Median overall survival was not reached for atezolizumab or pembrolizumab. Around 85% of patients suffered adverse effectsof some degree. Two of the patients treated with nivolumab developedvitiligo. Overall survival of both was higher than 2.5 years.Conclusions: For the patients included in the sample, nivolumab wasless effective in those with two or more metastases; the effectiveness ofpembrolizumab was lower in ECOG-2 patients. Vitiligo was related to amore durable response to treatment. (AU)

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer.

OBJECTIVE: To determine the effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in patients with non-small  cell lung cancer. METHOD: This is a retrospective observational study including patients treated in second line and beyond. The effectiveness of treatment  was assessed by means of overall survival and progression free survival  measurements. Toxicity was described according to the Common Criteria  for Adverse Event Terminology v5.0. RESULTS: The study included 8 patients treated with atezolizumab,19 with nivolumab, and 16 with pembrolizumab. Median progression free  survival with atezolizumab was 9.6 months (95%CI 2-17.2), 12.6 months (95%CI 6.9-18.2) for nivolumab, and 8.5 months (95%CI 0-19)  for pembrolizumab. Median overall survival was 13.4 months (95%CI 6- 20.9) for nivolumab. Both PFS and OS were statistically higher in patients  with grade 0-1 metastasis in the case of nivolumab, and in ECOG 0-1  patients for pembrolizumab. Median overall survival was not reached for  atezolizumab or pembrolizumab. Around 85% of patients suffered adverse  effects of some degree. Two of the patients treated with nivolumab  developed vitiligo. Overall survival of both was higher than 2.5 years. CONCLUSIONS: For the patients included in the sample, nivolumab was less  effective in those with two or more metastases; the effectiveness of pembrolizumab was lower in ECOG-2 patients. Vitiligo was related to a more durable response to treatment.

Objetivo: Efectividad y seguridad de atezolizumab, nivolumab y  embrolizumab en cáncer de pulmón no microcítico metastásico.Método: Estudio observacional retrospectivo en pacientes con cáncer de  pulmón no microcítico metastásico tratados en segunda línea o posteriores. La efectividad fue evaluada mediante supervivencia global y  supervivencia libre de progresión. La toxicidad mediante los Criterios Comunes de Terminología de Efectos Adversos v5.0.Resultados: Se incluyeron 8 pacientes con atezolizumab, 19 con  nivolumab y 16 con pembrolizumab. La mediana de supervivencia libre de progresión con atezolizumab fue 9,6 meses (intervalo de confianza del 95% [IC95%] 2-17,2), 12,6 meses (IC95% 6,9-18,2) para nivolumab 8,5 meses (IC95% 0-19) para pembrolizumab. La mediana de  supervivencia global con nivolumab fue 13,4 meses (IC95% 6-20,9) y no  se alcanzó para atezolizumab y pembrolizumab. Ambas fueron superiores  para los pacientes con 0-1 metástasis para nivolumab y en los pacientes  con ECOG 0-1 para pembrolizumab. Alrededor de un 85% de los pacientes sufrieron efectos adversos. Dos pacientes tratados con  nivolumab experimentaron vitíligo, con una supervivencia global mayor de  2,5 años.Conclusiones: En la muestra analizada, la efectividad de nivolumab es  menor en pacientes con dos o más metástasis, y la de pembrolizumab es  menor en pacientes con ECOG 2. La aparición de vitíligo se relacionó con  una respuesta duradera.

Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study.

Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6-3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of ≥38.2°C and an ANC of ≤500/m3. The number of patients who received prophylactic treatment with granulocyte colony-stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G-CSF compared with those who did not (5.0 days; IQR, 4.0-9.0 vs. 7.0 days; IQR, 5.0-11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0-7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0-12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN.

Spanish Society of Medical Oncology consensus on the use of erythropoietic stimulating agents in anaemic cancer patients.

Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in nonresponders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended.