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Objectives Necitumumab is a second-generation, recombinant, human IgG1-type monoclonal antibody directed against EGFR approved for adult patients with metastatic squamous non-small cell lung cancer (NSCLC) in combination with gemcitabine and cisplatin. This study assessed the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) and carboplatin in combination with necitumumab as first-line therapy in patients with stage IV squamous NSCLC. Materials and methods The treatment regimen comprised triplet induction with necitumumab (800 mg) with nab-paclitaxel (100 mg/m2) and carboplatin (AUC 6 mg*min/mL) for 4 cycles, followed by doublet maintenance with necitumumab and nab-paclitaxel with a 3-weekly schedule until progressive disease or unacceptable toxicity. The primary endpoint of the study was objective response rate (ORR). Results Fifty-four patients were enrolled. Median age was 65 years (range, 47–80 years). The majority of the patients were male (n = 42 [77.8%]) with an ECOG PS of 1 (n = 42 [77.8%]). The ORR was 51% (n = 26/54), and the disease control rate was 78.4% (n = 40/54). Median overall survival (OS) was 15.5 months (95% confidence interval [CI]: 10.18–not calculable), and the OS rate at 12 months was 50.4% (95% CI: 29.0–68.4). Median progression-free survival was 5.6 months (95% CI: 4.24–7.69)]. The most frequently reported treatment-emergent adverse events were anemia (57.4%), fatigue (55.6%), neutrophil count decreased (55.6%), hypomagnesemia (44.4%), and rash (38.9%). Conclusion Necitumumab/nab-paclitaxel/carboplatin first-line therapy produced favorable efficacy outcomes with manageable toxicity in patients with stage IV squamous NSCLC. The safety profile was fairly comparable with previous necitumumab combination studies in lung cancer.

Background There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. Materials and methods A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2–7, 9–21) were given for 4–6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (Grade ≥3) or hematologic (Grade 4) AEs. Results Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17–35 months). Conclusions The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.

Introduction: Since the most common lung cancers are lung adenocarcinoma, squamous lung cancer (SLC) and the small cell lung cancer (SCLC), a comparative diferential expression between these types of lung cancer deserves investigation. Material and Methods: RNA-seq data were obtained for samples from tumoral and adjacent healthy tissue from adenocarcinoma (7 patients), SLC (8 patients) both from Hospital Regional (Malaga, Spain), and SCLC (14 patients) from EGA (European Genome Archive) with code EGAS00001000334. An automated workflow was designed for pre-processing, mapping against the human genome hg38, assessing differential expression, and sample comparison, taking into account that samples are matched by patient. Results: A total of 2853, 3686 and 4863 genes were differentially expressed in adenocarcinoma, SLC and SCLC, respectively. There are 933 genes having a similar expression in the three cancers. Among the genes with a specific expression in each cancer we have found: 5 genes in adenocarcinoma (C4BPB, IYD, MSLN, TMC5, TRDN), 4 in SLC (AZGP1, HSPB3, MSLN, TP63) and 11 in SCLC (ADCYAP1, AKR1C1, AKR1C2, AKR1C3, ALDH3A1, GPA33, LAMB3, MSLN, PRAME, TARP, TUBA1A). Also we have found a gene that is the most different among the three, MSLN, which presents a differential logFC2 of –6,42, –2,23 and 2,84 in adeno, SLC and SCLC, respectively. Conclusions: The specific differential expression of genes in three different lung cancers conform a set of putative biomarker genes with a possible use on future prognostic and diagnostic methods.

Introduction: Gene expression analysis need to use reference genes (RGs) to normalize the measurements. Ideally, a RG should be expressed in the same degree in all the studied tissues, that is why housekeeping genes usually are used. But it has been demonstrated that they are less invariant than what was thought. Objectives: To find a set of RGs in lung cancer. Methods: RNA-seq reads of healthy and tumoral samples from EGA (17 patients with small-cell lung cancer [SCLC]) and NCBI (50 patients with adenocarcinoma lung cancer) repositories were downloaded. Reads were processed with a novel algorithm developed by us based on the coefficient of variation (CV) to select the genes with a CV lower than 15% or 20%, and whose number of reads per transcript was higher than 10,000. Hence, the most stable RGs having the highest expression level were selected. Results: Using 10,000 reads and CV Conclusions: The set of reference genes has been extended in two lung cancers, which makes more detailed expression analysis possible.

The optimal schedule and regimen of chemotherapy (CT) in association with chemoradiation has not been established in stage III non-small-cell lung cancer (NSCLC). We have compared three schedules of non-platinum-based CT plus either radiotherapy or chemoradiation. From May 2001 to June 2006, 158 patients with unresectable stage III NSCLC were enrolled in a randomized phase II trial with overall response rate (ORR) as the primary endpoint. The initial design included three arms: sequential CT followed by thoracic radiation (TRT); concurrent CT/TRT followed by consolidation CT; and induction CT followed by concurrent CT/TRT. However, based on the preliminary results of the RTOG 9410 trial, the sequential arm was closed when 19 patients had been enrolled. All patients received two cycles of docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8, as either induction or consolidation therapy. Concurrent CT/TRT consisted of docetaxel 20 mg/m(2) and carboplatin AUC 2 weekly plus 60 Gy TRT. No differences were found in ORR between the two arms (56% and 57%). Hematological toxicity was mild but significantly superior with consolidation CT; the esophagitis rate was similar in both arms (16% and 15%). With a median follow-up of 57 months, no differences were found in median survival (13.07 and 13.8 months) or 5-year survival (16.4% and 22%). This regimen cannot be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data (ClinicalTrials.gov NCT01652820).

Summary Objective We conducted a phase II trial to evaluate the efficacy and toxicity of a combination consisting of second-line docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients and methods Eligibility criteria: histologically confirmed advanced NSCLC with progressive disease to platinum-based chemotherapy, ECOG performance status (PS) 0 or 1, and adequate kidney, liver and bone marrow function. Treatment consisted of docetaxel 36 mg/m2 i.v. over 60 min followed by gemcitabine 1000 mg/m2 i.v. over 30 min on days 1 and 8 of each 3-week cycle for a planned six cycles or unacceptable toxicity. Results Of the 52 patients enrolled, 50 were evaluable for response and toxicity. The mean age was 59 years (range 42–79), 46 male and 4 female. Histology subtypes were: adenocarcinoma 26 patients, bronchioloalveolar 1 patient, large cell carcinoma 5 patients, and squamous cell carcinoma 18 patients. Thirty-eight patients had ECOG PS 1 and 12 patients had PS 0. The median number of cycles administered was four (range 2–6). The overall response rate was 28%. The median follow-up was 9 months (range 5–34 months). The median survival time (MST) was 8.2 months (95% CI, 4–12%), and the 1-year survival was 25%. The median progression-free survival was 4.4 months (95% CI, 2–6%). In the Cox regression model, survival was only significantly affected by the PS. The median survival in patients with PS 0 was 17.8 months (95% CI, 18.8–21.8%) compared with a median survival for patients with PS 1 of 6.1 months (95% CI, 4.1–8.2%) (P = 0.0057). Toxicity: three patients had grade 3 anemia, three patients had grade 3 thrombocytopenia, four patients had grade 3 neutropenia and only one patient developed grade 4 febrile neutropenia. Non-hematologic toxicity was also mild; the most frequent was asthenia, with grade 3 in eight patients (16%), and one patient with grade 4. Conclusion This regimen of docetaxel in combination with gemcitabine in advanced second-line NSCLC is an active and safe regimen.