XM02, the First Biosimilar G-CSF, is Safe and Effective in Reducing the Duration of Severe Neutropenia and Incidence of Febrile Neutropenia in Patients with Small Cell or Non-small Cell Lung Cancer Receiving Platinum-Based Chemotherapy

BackgroundRecombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia. The aim of the study was to show that a new granulocyte colony-stimulating factor, XM02, is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer.Patients and methodsA total of 240 patients receiving platinum-based chemotherapy were randomized in cycle 1 to treatment with daily injections (subcutaneous 5 µg/kg/d) of XM02 (n = 160) or Filgrastim Neupogen (n = 80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02.ResultsThe mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim, respectively. In the analysis of covariance for duration of severe neutropenia in cycle 1, the estimated treatment difference “XM02 minus Filgrastim” was 0.157 days, with 95% confidence level (−0.114 days, 0.428 days), which was included in the prespecified equivalence range (−1, 1). There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim (p = 0.2347). The adverse event profile was similar between XM02 and Filgrastim.ConclusionXM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the doses applied in this study

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: A subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit.Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033).Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.The sponsor of the FLEX study was Merck KGaA. Jim Heighway of Cancer Communications and Consultancy (Knutsford, UK) provided medical writing services on behalf of the study sponsor.Peer Reviewe

Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer – A retrospective single institution analysis

SummaryPurposeThe aim of this retrospective study is to present data on clinical significance of lactate dehydrogenase (LDH) serum levels in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).Patients and methodsFrom June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed LD and ED SCLC. 397 cases were identified. We collected data on patient characteristics including clinical performance status and LDH serum levels, metastatic sites, efficacy of first line chemotherapy and survival.ResultsIn both limited and extensive disease SCLC, elevated LDH serum levels resulted in significantly shorter median survival. The effect was most pronounced if levels were 300 U/l or higher. In patients with limited disease and normal LDH levels, median survival was 18.0 months. If LDH was higher than 300 U/l, overall survival was reduced to 12 months. In cases with extensive disease, overall survival was significantly lower in patients with elevated LDH serum levels with an additional reduction in overall survival in patients with LDH levels above 300 U/l. (7.0 vs. 12.0 months, p = <0.001). Multivariate Cox regression analyses revealed LDH levels to be an independent predictor of mortality after adjustment for age and Performance Status in LD and ED SCLC (HR 1.003, p = 0.017; HR 1.001, p = 0.002 respectively). However, categorizing LDH levels revealed no significant difference in LD SCLC.ConclusionIn our contemporary comprehensive patient population, LDH is proved to be a strong, independent predictive factor of median survival in patients with LD and ED SCLC