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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., Competing Interests: DR-A declares having received honoraria for lectures and advisory boards from Bristol-Myers-Squibb, Merck Sharp & Dohme, Hoffmann-La Roche, Pierre-Fabre, Novartis, Boehringer, Pfizer, Lilly, and AstraZeneca. OJ declares that he has received payment for advisory services from Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli Lilly, Abbvie, and Takeda. MP reports having received payments from Bristol-Myers Squibb, AstraZeneca, Takeda, Merck Sharp & Dohme, Hoffmann-La Roche, and Novartis for advisory services. JC received fees for advisory services from Hoffman-La Roche. CR declares having received lecture fees from Merck Sharp & Dohme and AstraZeneca, advisory board payments from Archer, Iceivafa, Merck Sharp & Dohme and Laboratorios Serono, and honoraria for consultancy roles from Mylan and Oncompass. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jantus-Lewintre, Massutí Sureda, González Larriba, Rodríguez-Abreu, Juan, Blasco, Dómine, Provencio Pulla, Garde, Álvarez, Maestu, Pérez de Carrión, Artal, Rolfo, de Castro, Guillot, Oramas, de las Peñas, Ferrera, Martínez, Serra, Rosell and Camps.)

Introduction: Precision medicine has revolutionized the understanding and treatment of cancer by identifying subsets of patients who are amenable to specific treatments according to their molecular characteristics, as exemplified by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Although tissue biopsy is the gold standard for determining molecular alterations in tumors, its limitations have prompted the development of new techniques for studying tumor biomarkers in liquid biopsies, such as mutation analysis in cell-free DNA (cfDNA). cfDNA analysis can accurately determine tumor progression and prognosis and more effectively identify appropriate targeted therapies. However, cfDNA is vulnerable, particularly during plasma sample shipping., Objective: We compared the cell- and DNA-stabilizing properties of cell-free DNA blood collection tubes (BCTs) with those of the traditional shipping method (frozen plasma) for EGFR mutation testing using the cobas ® EGFR Mutation Test v2 in a prospective cohort of 49 patients from three different Spanish hospitals., Methods: In total, 98 NSCLC samples, two from each patient, were studied; five of the 49 cases were considered invalid by cobas ® with one of the two shipping methods analyzed. After excluding these samples, we analyzed 88 samples from 44 patients. Considering the current methodology (frozen plasma) for sending samples as the gold standard, we evaluated the sensitivity and specificity of cfDNA BCT shipment., Results: The global agreement between the two methods was 95.4%, with 100% sensitivity and 94.6% specificity for the cfDNA BCTs. cfDNA BCTs had a positive predictive value of 81.8% and negative predictive value of 100%., Conclusion: cfDNA BCTs have the same sensitivity for EGFR mutation analysis in liquid biopsy as the current methodology and very high specificity. They also have some additional advantages in terms of collection and further shipment. Therefore, cfDNA BCTs can be perfectly incorporated into the routine practice for EGFR mutation determination., Funding: Roche Farma S.A., Spain.

Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC). The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting., Material and Methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomized1:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS)., Results: One hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688)., Conclusions: Our findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Lung cancer chemotherapy decisions in patients ≥ 70 years old are complex because of toxicity, comorbidity and the limited data on patient preferences. We examined the relationships between preferences and chemotherapy use in this group of patients., Methods and Patients: We used a questionnaire describing four hypothetical lung cancer treatment options. Eighty-three elderly (≥ 70 years old) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options. Patients had previously been included in a prospective study to explore geriatric evaluation in an oncology unit and all had given written informed consent., Results: Older patients (n=83) diagnosed with lung cancer (non-small- and small-cell lung cancer) from January 2006 to February 2008 were recruited from a single centre. The mean patient age was 77 years (range: 70-91). Eighty-one patients (97.6%) were men. Non-small-cell lung cancer (NSCLC) was the diagnosis in 63 patients (76%). Most patients selected active treatment (38.6% most survival benefit, 18% less survival benefit) and 31.3% selected no active treatment. Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities. Although most of the patients were symptomatic at diagnosis, the "symptom relief" option was chosen less frequently than the options that could prolong survival. Factors significantly related to patients' attitude toward chemotherapy were age (p<0.001), frailty (p=0.0039), depression and poor performance status (PS)., Conclusion: Elderly lung cancer patients want to be involved in the decision-making process. Survival was the main treatment objective for more than half of the patients in this study. We have not found other published studies about elderly lung cancer patients' decisions about chemotherapy.

The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in patients with advanced non-small cell lung cancer both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haematological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg/m(2) ) on days 1 and 8. This schedule was repeated every 21 days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg/min./mL in patients under 70 years and 4 mg/min./mL in patients aged 70 or older. The data of 24 patients were treated for population modelling performed with the nonmem (University of California, San Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33 patients enrolled in the study. The carboplatin systemic exposure measured by the AUC (mg/min./mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger patients and older groups, respectively. No significant differences were observed between the two groups with respect to rates of grade 3+ anaemia, neutropenia or thrombocytopenia. In clinical practice, a target AUC of 4 mg/min./mL carboplatin is applied to patients aged 70 and over, but the actual systemic exposure to the drug is higher. This supports a target AUC of 4 mg/min./mL carboplatin for patients older than 70 years when the dose is calculated by means of the Calvert-Crokcoft-Gault formula., (© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.)

Background: Mean age of patients with lung cancer rises as a result of increasing life expectancy. So, the proportion of patients with serious comorbidity also increases [1,2]. Lung cancer treatment is characterized by a narrow therapeutic index. When life expectancy is short and therapeutic benefit is limited, it is of paramount importance to know the specific cause of death. Comorbidity is understood as a competing cause of death, and is the main exclusion criterion for lung cancer clinical trials. The aim of this study was to determine the prevalence of comorbidity in elderly lung cancer patients seen in an outpatient oncology department and to determine its correlation with survival., Patients and Methods: Between January 2006 and February 2008, 83 untreated lung cancer patients over the age of 70 years were enrolled in the study. Comorbidity was evaluated according to the Charlson comorbidity index (CCI) [3] and the simplified comorbidity score (SCS) [4]., Results: 83 patients (97.6% men, mean age 77 years) were studied. Comorbidities: tobacco consumption (94.6%), cardiovascular diseases (65%), and chronic obstructive pulmonary disease (COPD) (59%). Mean CCI was 3 (range 0-9). Mean SCS was 9 (range 4-19), and 47% of patients had an SCS>9. Comorbidity was fairly well correlated with age, ADL, IADL, and stage. Neither the CCI nor the SCS was related to survival (p: 0.47 and p: 0.24, log rank, respectively). Median survival was 326 days (95% CI, 259-393 days; or 10.8 months, 95% CI 8.6-13.1 months). Main cause of death was lung cancer disease progression (69.5%, 57 patients), with 20 patients (25%) dying of other non-neoplastic causes. Stage was significantly associated with survival (log rank: p<0.001)., Conclusions: Although there was a high prevalence of comorbidity in our population, comorbidity was not related to survival. Comorbidity is one of the main reasons for undertreatment of elderly lung cancer patients, but this study indicates that this undertreatment may not be warranted given that those comorbidities may not cause a patient's death. Our data generated more of a hypothesis than a conclusion. Comorbidity should be an impetus for treatment design instead of an exclusion criterion for oncologic treatment., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients., Patients and Methods: 348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age., Results: ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032)., Conclusion: Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.