Search

PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC. Several PD-(L)1 inhibitors have been approved or are in development for the treatment of NSCLC, showing promising efficacy and tolerable safety profiles. Here, the authors present a randomized phase II clinical trial comparing two different anti-PD-1 antibodies, dostarlimab and pembrolizumab, both combined with chemotherapy as first-line treatment in patients with metastatic NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown improved tolerability with once-weekly versus three-weekly docetaxel in the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the tolerability of nintedanib plus weekly docetaxel in patients with NSCLC. Methods: This phase I, open-label, dose-escalation study (NCT02668393) enrolled patients with locally advanced/metastatic adenocarcinoma NSCLC that had progressed on first-line platinum chemotherapy. The primary endpoint was to determine the maximum tolerated dose of nintedanib (up to 200 mg twice daily [BID]) combined with weekly docetaxel (35 mg/m2) on days 1, 8, and 15 based on the occurrence of dose-limiting toxicities (DLTs) over a 28-day treatment cycle. Adverse events (AEs) were also evaluated. Results: The trial terminated prematurely due to recruitment challenges. At termination, seven patients had received nintedanib 150 mg BID and seven nintedanib 200 mg BID, in combination with weekly docetaxel. In the first treatment cycle, DLTs were reported for 1/6 evaluable patients (16.7%) in each group. The disease control rates were 57.1% and 42.9%, respectively. Grade ≥3 treatment-related AEs affected three patients in each group (42.9%); neutropenia was reported in one patient (14.3%) in each group. Treatment-related serious AEs were reported in three patients (42.9%) receiving nintedanib 150 mg, and two patients (28.6%) receiving nintedanib 200 mg. Conclusions: Overall, nintedanib plus weekly docetaxel was well-tolerated in patients with locally advanced or metastatic lung adenocarcinoma who progressed on first-line platinum-based chemotherapy, without loss of efficacy. DLTs were manageable. [ABSTRACT FROM AUTHOR]

In CheckMate 9LA (NCT03215706), first-line nivolumab plus ipilimumab with chemotherapy (2 cycles) significantly improved overall survival versus chemotherapy (4 cycles) in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor / anaplastic lymphoma kinase alterations. We present exploratory patient-reported outcomes (PROs; minimum follow-up, 2 years). In patients (N = 719) randomised 1:1 to nivolumab plus ipilimumab with chemotherapy or chemotherapy alone, disease-related symptom burden and health-related quality of life were assessed using the Lung Cancer Symptom Scale (LCSS) and 3-level EQ-5D (EQ-5D-3L). Treatment-phase changes in LCSS average symptom burden index (ASBI), LCSS three-item global index (3-IGI) and EQ-5D-3L visual analogue scale (VAS) and utility index (UI) over time were analysed descriptively and using mixed-effect model repeated measures. Time-to-deterioration/improvement analyses were conducted. Treatment-phase PRO questionnaire completion rates were >80%. Mean treatment-phase changes showed no deterioration from baseline in both arms for LCSS ASBI/3-IGI and EQ-5D-3L VAS/UI; however, minimally important differences were not met. Mixed-effect model repeated measures analyses showed overall reduction in symptom burden from baseline for both arms; changes from baseline for LCSS 3-IGI and EQ-5D-3L VAS/UI were numerically improved with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, but minimally important differences were not met. Nivolumab plus ipilimumab with chemotherapy delayed time-to-definitive-deterioration versus chemotherapy (LCSS ASBI: hazard ratio, 0.62 [95% confidence interval, 0.45–0.87]); results were similar across PRO measures. At 2-year minimum follow-up, first-line nivolumab plus ipilimumab with chemotherapy reduced the risk of definitive deterioration in disease-related symptom burden and health-related quality of life versus chemotherapy and maintained QoL in patients with metastatic non-small cell lung cancer. Clinical trial registration: ClinicalTrials.gov Identifier, NCT03215706. • Patient-reported outcomes were assessed using the Lung Cancer Symptom Scale and EQ-5D in CheckMate 9LA. • Risk of symptom deterioration was lower with nivolumab + ipilimumab + chemo versus chemo. • 1L nivolumab + ipilimumab + chemo maintained quality of life in patients versus chemo. • Data confirm clinical benefit of 1L nivolumab + ipilimumab + chemo in metastatic non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

We report 5-year efficacy and safety outcomes from CheckMate 9LA in patients with metastatic non-small cell lung cancer (mNSCLC) and exploratory analyses in key patient subgroups. Adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to receive nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Outcomes were assessed in all randomized patients and subgroups. With 57.3 months' minimum follow-up, patients continued to derive overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy over chemotherapy (HR, 0.73; 95% CI, 0.62–0.85; 5-year OS rates, 18% vs. 11%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 < 1%, 22% vs. 8%; PD-L1 ≥ 1%, 18% vs. 11%), histology (squamous, 18% vs. 7%; non-squamous, 19% vs. 12%), or presence of baseline brain metastases (20% vs. 6%). Five-year duration of response (DOR) rates were 19% versus 8% with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, with consistent benefit across subgroups. Patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events had a 5-year OS rate of 37%. Five-year progression-free survival and DOR rates in 5-year survivors were 55% versus 38% and 59% versus 46%, respectively. No new safety signals were observed in 5-year survivors, regardless of the number of ipilimumab doses received. This 5-year update supports the long-term, durable OS benefit and improved 5-year survivorship with nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with mNSCLC, regardless of tumor PD-L1 expression or histology. NCT03215706 • NIVO + IPI + chemo provided long-term, durable clinical benefit in metastatic NSCLC. • Magnitude of benefit was higher in PD-L1 < 1% or squamous histology subgroups. • NIVO + IPI + chemo improved efficacy outcomes in patients with brain metastases. • Treatment discontinuation due to TRAEs had no negative impact on efficacy. • In 5-y survivors, safety profile was consistent regardless of the no. of IPI doses. [ABSTRACT FROM AUTHOR]

Background: PERLA (NCT04581824) is a global, randomized, phase 2, double-blind study assessing the efficacy and safety of chemotherapy plus dostarlimab (dostCT) or chemotherapy plus pembrolizumab (pembCT) as first-line treatment for patients with metastatic nonsquamous non-- small cell lung cancer (NSCLC). Previous results showed that dostCT had similar efficacy and safety to pembCT.1 Objective: To examine and report patient-reported outcomes (PROs) from patients with NSCLC who received either dostCT or pembCT in the PERLA trial. Methods: Patients with Eastern Cooperative Oncology Group performance status 0/1 (fully active or active but restricted in physically strenuous activity) were randomized 1:1 to receive dostCT or pembCT every 3 weeks for up to 35 cycles. PROs were collected at baseline, every 3 weeks until cycle 4, every 9 weeks until cycle 16, every 12 weeks until end of treatment, and at the 30-day safety follow-up. PRO questionnaires, the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13, were used to measure patients' perspectives on symptoms and their impacts; QLQ-C30 is a health-related quality-of-life assessment for any cancer, and QLQ-LC13 is lung-cancer specific. Changes in patients' scoring from baseline were described and were analyzed using a longitudinal mixed model. Leastsquares means were calculated to quantify change observed over time. Changes of ≥10 points were considered clinically meaningful. Time to deterioration (TTD) in scores from QLQ-C30 and selected QLQ-LC13 symptoms were estimated using Kaplan-Meier statistical methods. Results: Analysis populations for QLQ-C30 and QLQLC13 included 102 and 96 patients from the dostCT arm, respectively, and 99 and 90 patients from the pembCT arm, respectively. QLQ-C30 and QLQ-LC13 completion rates at cycle 13 (C13; ≈1 year of treatment) were 55.0% and 54.2%, respectively, for dostCT, and 37.1% and 35.7%, respectively, for pembCT. Scores for both questionnaires remained stable from baseline to C13, including function subscales (eg, physical, role) and symptom subscales (eg, pain, cough, dyspnea). No clinically meaningful differences between treatment arms in changes from baseline were observed. Across most subscales, >60% of patients in both arms showed stable or improved responses up to C13. At C13, more patients in the dostCT arm versus the pembCT arm reported meaningful improvements in chest pain (34.4% vs 10.0%, respectively) and dyspnea (40.6% vs 25.0%, respectively). TTDs were comparable between treatment arms, except for dyspnea (4.24 mo, dostCT vs 1.54 mo, pembCT). Conclusions: Health-related quality of life, as measured by PRO questionnaires, was similar and stable through C13 in both treatment arms. Results supplement the efficacy and safety data from PERLA1 and support further investigation of dostarlimab as an appropriate programmed cell death 1 inhibitor for use in combination with standard of care and novel therapies in metastatic NSCLC. Funding: This study was sponsored by GSK. Editorial support was provided by ArticulateScience, LLC, funded by GSK. [ABSTRACT FROM AUTHOR]

In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). To evaluate patient-reported outcomes (PROs) in this population. Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4–22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. Clinical trial registration: NCT02477826. • Nivolumab + ipilimumab improved patient-reported outcomes versus chemotherapy in non–small-cell lung cancer. • Improvements were seen in lung cancer symptoms and in general health status. • Improvements with nivolumab + ipilimumab were rapid and durable. • Disease-related symptom deterioration was delayed with nivolumab + ipilimumab. [ABSTRACT FROM AUTHOR]

Background: Nintedanib in combination with docetaxel is approved in the European Union and other countries for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) of adenocarcinoma histology after first-line chemotherapy, based on the overall survival findings of Phase III LUME-Lung 1 study. Change in target lesion size over time as a treatment effect was assessed in patients from this study. Methods: Tumor size was evaluated using predefined tumor measurements. Mixed-effects models were used to quantify individual relationships between time from randomization and tumor burden, measured as the sum of longest diameter (SLD) of target lesions and assessed by an independent review (Response Evaluation Criteria In Solid Tumors [RECIST] v1.0). Exploratory analyses were conducted on the overall adenocarcinoma population, adenocarcinoma patients with time from start of first-line therapy <9 months (TSFLT <9), adenocarcinoma patients who had progressive disease as best response to first-line therapy (PD-FLT), and in squamous cell carcinoma patients. Results: Estimated mean baseline SLD was 82.5 mm in the adenocarcinoma (n=658), 88.3 mm in the TSFLT <9 (n=405), 98.1 mm in the PD-FLT (n=117), and 94.3 mm in the squamous cell carcinoma (n=555) populations. Treatment with nintedanib/docetaxel showed a significant reduction in tumor size over time (P<0.0001) in patients with adenocarcinoma compared with placebo/docetaxel, and in patients with squamous cell carcinoma (P=0.0049). Treatment difference at 6 months was 9.7 mm in the overall adenocarcinoma population, 16.8 mm in the TSFLT <9 population, 19.7 mm in the PD-FLT population, and 6.8 mm in the squamous cell carcinoma population. SLD at 2 months post-randomization was identified as a surrogate endpoint for overall survival, in addition to progression-free survival, for all except the PD-FLT population. Conclusion: Treatment with nintedanib/docetaxel significantly decreased tumor burden and decelerated tumor size over time compared with placebo/docetaxel in the overall adenocarcinoma population, including in patients with the poorest prognosis due to aggressive tumor dynamics. [ABSTRACT FROM AUTHOR]

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. [ABSTRACT FROM AUTHOR]

The article focuses on the aspects of the treatment and precision diagnosis of advance non-small-cell lung cancer (NSCLC). Topics discussed include the importance of the pathological features of the cancer on determining the treatment options, the staging of the lung cancer based on the correct tumor-node-metastasis (TNM), and several treatment options for NSCLC such as platinum-based chemotherapy.

Background: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).Methods: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.Results: Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).Conclusions: In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .). [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC), which accounts for 10%-15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Although up to 80% of patients respond to first-line chemotherapy, most eventually relapse, and there are no approved agents beyond the second line. Despite the high incidence of mutations in SCLC, to date no targeted therapy has shown a benefit for this patient population, and systemic treatment has not changed significantly during the past 3 decades. Given that extensive-stage SCLC has a 5-year survival rate of only 1%-2%, novel therapies are desperately needed. Recent evidence shows that the immune system is capable of generating antitumor responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable therapeutic approach to the treatment of patients with SCLC. Of the immunotherapies being investigated for patients with SCLC, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are perhaps the most promising. Because these immune checkpoint pathways, which under normal circumstances function to protect healthy tissues from damage during inflammatory responses and maintain self-tolerance, can help tumor cells evade elimination by the immune system, they represent potential therapeutic targets. This review discusses the rationale for immunotherapy and the early clinical results of immunotherapeutic agents being investigated in SCLC. [ABSTRACT FROM AUTHOR]

There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy. [ABSTRACT FROM AUTHOR]

Summary The MAP-kinase pathway, consisting of the kinases RAS, RAF, MEK, and ERK, is crucial for cell proliferation, inhibition of apoptosis, and migration of cells. Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC). Due to their structure and function, the MEK proteins are attractive targets for cancer therapy and are also under investigation in NSCLC. We discuss strategies of targeting the RAS-RAF-MEK-ERK pathway with emphasis on MEK inhibition, either alone or in combination with other targets or conventional chemotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Vascular endothelial growth factor (VEGF)-mediated angiogenesis plays an important role in non-small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC. METHODS Eligible stage IV nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were randomized 1:1 to pemetrexed and carboplatin (or cisplatin) or ramucirumab (10 mg/kg) plus pemetrexed and carboplatin (or cisplatin) once every 3 weeks. Treatment was given for 4 to 6 cycles, and this was followed by a maintenance phase with pemetrexed or ramucirumab and pemetrexed. The primary endpoint was progression-free survival (PFS) with a sample size of sufficient power to detect an increase from 7 to 10.4 months. RESULTS From October 2010 to October 2011, 140 patients were randomized (pemetrexed-platinum arm, 71; ramucirumab-pemetrexed-platinum arm, 69), and most baseline characteristics were similar for the 2 treatment arms. The median PFS was 5.6 months for the pemetrexed-platinum arm and 7.2 months for the ramucirumab-pemetrexed-platinum arm (hazard ratio, 0.75; P = .132). The objective response rates were 38.0% and 49.3% for the pemetrexed-platinum and ramucirumab-pemetrexed-platinum arms, respectively ( P = .180). The disease control rate was 70.4% for the pemetrexed-platinum arm and 85.5% for the ramucirumab-pemetrexed-platinum arm ( P = .032). The grade 3 or higher adverse events occurring in 10% or more of patients were thrombocytopenia, neutropenia, fatigue, anemia, nausea, back pain, and hypertension. CONCLUSIONS The primary endpoint of significant prolongation of PFS was not met; however, ramucirumab showed evidence of clinical activity in combination with pemetrexed and platinum in nonsquamous NSCLC patients. The addition of ramucirumab to pemetrexed and platinum did not result in new or unexpected safety findings. Cancer 2015;121:883-892. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives ABIGAIL, a phase II, randomized, open-label, multicenter study evaluated the correlation between biomarkers and best overall response (BOR) to bevacizumab with chemotherapy in patients with advanced or recurrent non-small-cell lung cancer (NSCLC). Exploratory analyses of vascular endothelial growth factor (VEGF) clinical genotyping data are presented. Materials and methods A total of 303 patients with NSCLC were randomized to receive bevacizumab 7.5 mg/kg or 15 mg/kg until progression or unacceptable toxicity (plus six cycles of chemotherapy). Patients provided blood samples for biomarker analysis. Exploratory analyses were conducted to assess whether genetic variants in VEGF-A or VEGFR-1/-2 act as efficacy or safety biomarkers. Single nucleotide polymorphisms (SNPs) were determined using individual genotyping assays. DNA analysis for 12 SNPs across three genes is reported: VEGF-A (five SNPs), VEGFR-1 (three SNPs), and VEGFR-2 (four SNPs). Results VEGF-A: c.+405/c.−634 (CG), VEGF-A: c.−460 >C; c−1498 >C (CT), and VEGF-A: c.−2578 C>A were associated with >50% higher odds of responding to treatment. VEGFR-1: rs9554316 (GT) was associated with >30% higher risk of progression and >40% higher risk of death. VEGF-A: c.+936 C>T was associated with higher incidence of hypertension. Conclusions Four genetic variants of VEGF-A and VEGFR-1 were associated with bevacizumab treatment outcome. Three variants in VEGF-A were associated with increased BOR, one variant in VEGFR-1 was associated with worse progression-free survival/overall survival. These associations were not statistically significant after correction for multiple testing. No genetic variant was associated with significantly higher risk of hypertension. Replication in additional studies may provide insight into the use of these variants to predict response to bevacizumab. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Tigatuzumab, a humanized monoclonal DR5 agonist antibody induces apoptosis in human cancer cell lines. The objective of this study was to investigate the antitumor effects of tigatuzumab combined with carboplatin/paclitaxel in chemotherapy-naïve patients with metastatic/unresectable non-small cell lung cancer (NSCLC). Methods: Patients with histologically or cytologically confirmed NSCLC stage IIIB/IV disease by RECIST (version 1.0) and ECOG-PS 0–1 were enrolled at 15 European sites. Patients received tigatuzumab or placebo intravenously with carboplatin/paclitaxel every 3 weeks (1 cycle) for up to 6 cycles. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate and safety. Results: 97 patients were analyzed for efficacy (49 tigatuzumab; 48 placebo). Median PFS (95% CI) was 5.4 months (3.3, 6.6) for tigatuzumab compared with 4.3 months (4.1, 5.8) for placebo. Median OS (95% CI) was 8.4 months (6.9, 16.3) for tigatuzumab versus 9.0 months (7.6, 14.5) for placebo. 12 patients (24.5%) in the tigatuzumab arm and 11 patients (22.9%) in the placebo arm had partial response. No patient had complete response. In a prospectively-defined Fc gamma receptor genotype subset (n =25), there was a non-significant trend toward increased PFS with tigatuzumab versus placebo (HR=0.47; 95% CI: 0.16, 1.35) but no difference in OS. Tigatuzumab was well tolerated. However, grade 3/4 neutropenia was reported in 10 patients (20.4%) receiving tigatuzumab compared with 4 patients (8.3%) receiving placebo. Conclusions: Tigatuzumab was well tolerated but did not improve efficacy of carboplatin/paclitaxel in systemic therapy-naïve, unselected advanced NSCLC patients. Clinical trials identifier: NCT00991796. [Copyright &y& Elsevier]

Abstract: Introduction: This phase II study assessed the efficacy and safety of oral vinorelbine given weekly in combination with carboplatin (CBDCA) AUC 5 once every 3 weeks for four cycles in chemonaive patients with advanced non-small cell lung carcinoma (NSCLC), followed by consolidation therapy with single-agent oral vinorelbine in non-progressive patients. Methods: Chemonaive advanced NSCLC patients received four cycles of combination therapy with CBDCA AUC 5 day 1 and oral vinorelbine, 60mg/m2 on days 1, 8 and 15 (cycle 1), dose increased to 80mg/m2 (cycles 2–4) in absence of grades 3–4 neutropenia (NCI-CTCv2). Consolidation therapy with oral vinorelbine was continued (cycle 5) at same dosage; if dose was decreased during combination therapy, it was given at 60mg/m2, then increased at 80mg/m2 (cycle 6) in absence of grades 3–4 neutropenia until PD, toxicity or patient''s refusal. Results: A total of 57 patients were registered and 56 patients were treated (ITT population), median age was 61 years (37–71). Objective response evaluated by RECIST was 17.9% (95% confidence interval, CI [8.9–30.4]) and disease control (CR, PR, NC) 73.2% (95% CI [59.7–84.2]), median progression-free survival 4.3 months (95% CI [3.1–5.1]) with median overall survival 9.7 months (95% CI [7.7–11.9]) and 1-year survival 37.1% (95% CI [24.4, 49.9]). Grades 3–4 neutropenia occurred in 67.9% of patients during combination and 20% during consolidation; febrile neutropenia occurred in 4 patients (7.1%) during combination therapy. Non-hematological toxicities occurred primarily during combination (grade 3 nausea and grade 3 vomiting in 7.1% of patients). Conclusions: The combination of oral vinorelbine given weekly in 3-week cycles in combination with carboplatin followed by consolidation therapy with oral vinorelbine as a single-agent was able to achieve efficacy results in line with other doublets including carboplatin in terms of response as well as survival. This regimen reported a good profile of tolerability in the treatment of advanced NSCLC, allowing that this combination can be easily proposed for the palliative care of NSCLC patients where the advantages of carboplatin over cisplatin are still appreciated. [Copyright &y& Elsevier]

Summary: Chemotherapy has reached a therapeutic plateau in the treatment of advanced non-small cell lung cancer (NSCLC), and effective, better-tolerated treatment strategies are needed. An improved understanding of the molecular processes underlying tumor biology has led to the development of therapies that target these processes. Intracellular signaling pathways related to the vascular endothelial growth factor and the epidermal growth factor receptor both play a central role in tumorigenesis as well as tumor growth, and are therefore rational targets for anti-cancer drug development. Various agents that target these pathways are in clinical development. Some of these have already changed treatment practice in NSCLC, most notably the monoclonal antibody, bevacizumab, in combination with chemotherapy in the first-line setting and the small-molecule tyrosine-kinase inhibitors, erlotinib and gefitinib, in the second-line setting. We will review the clinical data for various novel therapies and identify how these agents are improving outcomes in the first- and second-line treatment of advanced NSCLC. [Copyright &y& Elsevier]

Background: CheckMate 227 (NCT02477826) is a large phase 3 study of first-line nivolumab or nivolumab-based regimens vs chemotherapy in advanced NSCLC. Objectives: Here we report results from Part 1, including a preplanned coprimary end point evaluating progression- free survival (PFS) of nivolumab + ipilimumab vs chemotherapy in patients with high TMB (≥10 mut/ Mb), safety of nivolumab + low-dose ipilimumab, and patient-reported outcomes (PROs). Methods: Patients (N = 1739) with chemotherapy-naive, stage IV/recurrent NSCLC without known sensitizing EGFR/ALK alterations were randomized 1:1:1 to nivolumab (3 mg/kg every 2 weeks [Q2W]) + ipilimumab (1 mg/kg Q6W), nivolumab monotherapy (240 mg Q2W), or chemotherapy for patients with ≥1% tumor programmed death-ligand 1 (PD-L1) expression and to nivolumab + ipilimumab, nivolumab (360 mg Q3W) + chemotherapy, or chemotherapy for patients with <1% tumor PD-L1 expression. Coprimary end points were overall survival for nivolumab + ipilimumab vs chemotherapy in patients with PD-L1--selected tumors and PFS (blinded independent central review) for nivolumab + ipilimumab vs chemotherapy in patients with high TMB ≥10 mut/Mb. TMB was determined from tumor tissue using the FoundationOne CDx assay. Safety analyses included time to onset and time to resolution of select treatment-related adverse events (select TRAEs; those with a potential immunologic cause) and corticosteroid use. PROs were assessed using the Lung Cancer Symptom Scale and EQ-5D instruments. Results: Minimum follow-up was 11.2 months. PFS was significantly longer with nivolumab + ipilimumab vs chemotherapy in patients with high TMB ≥10 mut/ Mb (HR = 0.58 [97.5% CI, 0.41-0.81]; P = .0002); results were consistent across subgroups, including PD-L1 expression and tumor histology. Rates of TRAEs leading to discontinuation were 17% with nivolumab + ipilimumab and 9% with chemotherapy. Grade 3/4 TRAEs were reported in 31% and 36% of patients treated with nivolumab + ipilimumab and chemotherapy, respectively. Grade 3/4 select TRAEs by category with nivolumab + ipilimumab included hepatic (8%), endocrine (4%), and skin (4%), and were consistent with previous reports. Median time to onset of select TRAEs ranged from 2 to 15 weeks, and the majority resolved (median time to resolution, ≤10 weeks). PRO results will be reported in the final presentation. Conclusions: First-line nivolumab + ipilimumab significantly prolonged PFS vs chemotherapy in patients with NSCLC and high TMB ≥10 mut/Mb regardless of PD-L1 expression. These results validate the role of TMB as a biomarker for the use of nivolumab + ipilimumab in first-line NSCLC. Safety of nivolumab + lowdose ipilimumab was manageable. Prior Presentation at Congress: Abstract is an adaptation from data originally presented in part at the 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL, USA, and the American Association for Cancer Research Annual Meeting, April 14-18, 2018; Chicago IL, USA. The adapted abstract has been submitted to: German Society for Hematology and Medical Oncology 2018, International Association for the Study of Lung Cancer Latin America Conference on Lung Cancer 2018, Sociedad Española de Oncología Médica 2018, and American Society of Clinical Oncology Quality Care Symposium 2018. [ABSTRACT FROM AUTHOR]

Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0–1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov , NCT03191786. Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4–11·9] vs 9·2 months [5·9–11·2]; stratified hazard ratio 0·78 [0·63–0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3–29·4) with atezolizumab compared with 12% (6·7–18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3–4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. F Hoffmann-La Roche and Genentech Inc, a member of the Roche group. [ABSTRACT FROM AUTHOR]

Objectives We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC). Materials and methods Patients in this multicenter, open-label, parallel-group, non-comparative Phase 2 study were randomized (1:1) to pemetrexed (500 mg/m 2 ) with either cisplatin (75 mg/m 2 ) or carboplatin (AUC5) for 4 cycles of 21 days. The primary endpoint was treatment feasibility (defined as 4 cycles completed with no cycle delay >42 days and ≤2 dose reductions, with a median relative dose intensity (RDI) ≥95% [overall]; and no Grade ≥3 toxicities at the follow-up visit 30 days after last drug administration). Secondary objectives included overall survival (OS) and safety. Results We randomized 122 patients and treated 118. 71.9% (46/64) of patients in pemetrexed + cisplatin and 88.9% (48/54) in pemetrexed + carboplatin completed 4 cycles (median RDI >97% for all compounds). Neither treatment met the pre-defined feasibility level >60% of patients: 59.4% (95% confidence interval [CI]: 46.4;71.5) pemetrexed + cisplatin; 50.0% (95%CI: 36.1;63.9) in pemetrexed + carboplatin. In a post-hoc analysis considering only safety, both regimens were feasible with 81.3% (95%CI: 69.5;89.9) in pemetrexed + cisplatin and 90.7% (95%CI: 79.7;96.9) in pemetrexed + carboplatin. OS rates for both groups were 82–83% after 3 years and 80–83% after 5 years. Treatment-related Grade ≥3 adverse events (mostly hematological) were experienced by approximately 30% of patients in each group. Conclusion Although the study did not meet the primary objective, both treatment groups demonstrated good safety-related feasibility and tolerability as adjuvant treatment in patients with completely resected Stage IB/II NSCLC. [ABSTRACT FROM AUTHOR]

The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex) remains controversial. 110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016–2022 were analyzed. Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p = 0.004), more objective responses (ORR 49% vs. 28%, p = 0.086) and numerically longer overall survival (OS 16 vs. 10 months, p = 0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p = 0.018), particularly for never-smokers (p = 0.041). Higher PD-L1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32%, p = 0.088) and PFS (6 vs. 3 months, p = 0.160), as well as longer OS in multivariable analysis (HR=0.54, p = 0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p = 0.013; OS 16 vs. 13 months, p = 0.270). CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD. • Chemoimmunotherapy prolongs PFS compared to chemotherapy in METΔ14ex NSCLC. • IO monotherapy confer long responses and OS similar to that of CHT-IO. • PD-L1 expression does not correlate with immunotherapeutic efficacy. • TP53 mutations are linked to better IO outcomes and may assist therapeutic decisions. • The rate of second-line treatment in the real-world setting is approximately 50%. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs).Methods: In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries. Eligible patients had measurable disease (per RECIST version 1.1) and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks (35 cycles) or investigator-choice platinum-doublet chemotherapy (4-6 cycles or until documented disease progression or unacceptable toxicity). Randomisation was stratified according to geography, ECOG performance status, and histology. PROs were assessed at day 1 of cycles 1-3, every 9 weeks thereafter, at the treatment discontinuation visit, and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), the EORTC Quality of Life Questionnaire Lung Cancer 13 items (QLQ-LC13), and the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) questionnaire. The key exploratory PRO endpoints (analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint) were baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/quality-of-life (QOL) score and time to deterioration of the composite of cough, chest pain, and dyspnoea in the QLQ-LC13. This study is registered with ClinicalTrials.gov, number NCT02142738, and is ongoing but no longer enrolling patients.Findings: Between Sept 19, 2014, and Oct 29, 2015, 305 patients were randomly assigned to pembrolizumab (n=154) or chemotherapy (n=151). Three patients in each group did not complete any PRO instruments at any timepoints, and so 299 patients were included in the full analysis set. Of these patients, one in each group did not complete any PRO instruments before week 15, and so were not included in analyses of change from baseline to week 15. PRO compliance was greater than 90% at baseline and approximately 80% at week 15 for both groups. Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 (95% CI 3·3 to 10·6) for pembrolizumab and -0·9 (-4·8 to 3·0) for chemotherapy, for a difference of 7·8 (2·9 to 12·8; two-sided nominal p=0·0020). Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients (46 [31%] of 151 patients vs 58 [39%] of 148 patients). Time to deterioration was longer with pembrolizumab than with chemotherapy (median not reached [95% CI 8·5 to not reached] vs 5·0 months [3·6 to not reached]; hazard ratio 0·66, 95% CI 0·44-0·97; two-sided nominal p=0·029).Interpretation: Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy, and might represent a new first-line standard of care for PD-L1-expressing, advanced NSCLC.Funding: Merck & Co. [ABSTRACT FROM AUTHOR]

Objectives Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300 mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150 mg dose (E150). Materials and methods Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. Results A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 0.83–1.33; unstratified log-rank P = 0.671). Median OS was 6.8 months in both arms (unstratified HR = 1.03, 95% CI: 0.80–1.32; unstratified log-rank P = 0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Conclusions Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. [ABSTRACT FROM AUTHOR]

Objectives REVEL demonstrated that ramucirumab + docetaxel (RAM + DTX) improved overall survival, progression-free survival, and objective response rate in patients with advanced/metastatic non-small cell lung cancer with progression after platinum-based chemotherapy. This analysis examined quality of life (QoL) as assessed by the Lung Cancer Symptom Scale (LCSS) and clinician-reported functional status. Materials and Methods The LCSS includes 6 symptom and 3 global items measured on a 0–100-mm scale; higher scores represent greater symptom burden. LCSS and ECOG PS data were collected at baseline, every 3-week cycle, the summary visit, and at the 30-day follow-up. LCSS total score and Average Symptom Burden Index (ASBI) were calculated. The primary analysis compared time to deterioration (TtD) between treatment arms for all individual items and summary scores, defined as increase from baseline by ≥15 mm using the Kaplan-Meier method and Cox regression. TtD to ECOG PS ≥2 was analyzed. Results There were 1253 patients randomized to receive RAM + DTX or placebo + docetaxel (PL + DTX). Across all assessments, LCSS compliance was approximately 75% and balanced across arms. The mean (SD) baseline LCSS total score was 27.3 mm (17.08 mm) on RAM + DTX and 29.6 mm (17.59 mm) on PL + DTX. At 30-day follow-up, mean (SD) LCSS total score was 32.0 (19.03) on RAM + DTX and 32.5 (19.87) on PL + DTX. The TtD for all LCSS scores was similar between treatment arms. Stratified HRs (95% CI) for LCSS total score and ASBI were HR = 0.99 (0.81, 1.22), p = 0.932 and HR = 0.93 (0.75, 1.15), p = 0.514 with approximately 70% of patients censored. TtD to PS ≥ 2 was similar between treatment arms (HR = 1.03 [95% CI: 0.85, 1.26], p = 0.743) with approximately two-thirds of the patients censored. Conclusion In addition to improvement of clinical efficacy outcomes demonstrated in REVEL, these results suggest that adding ramucirumab to docetaxel did not impair patient QoL, symptoms, or functioning. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Sagopilone is the first fully synthetic epothilone in clinical development and has proven preclinical activity in tumor models. This multicenter, randomized, open-label, phase II study examined the efficacy and safety of three regimens with two doses and two infusion durations of second-line sagopilone in pretreated patients with stage IIIB or IV non-small-cell lung cancer. Methods: Eligibility criteria included: at least one measurable lesion by modified response evaluation criteria in solid tumors; World Health Organization performance status of 0 or 1; and failure of previous platinum-based chemotherapy. Patients were randomized to receive: 16mg/m2 sagopilone over 3h (treatment arm A); 22mg/m2 sagopilone over 0.5h (treatment arm B); or 22mg/m2 sagopilone over 3h (treatment arm C). Treatment duration was two to six courses every 3 weeks; more than six treatment courses were permitted if there was sustained clinical benefit. The primary efficacy endpoint was best overall response after six courses; at least five confirmed responders per arm indicated a successful outcome. Results: In total, 128 patients (44, arm A; 41, arm B; 43, arm C) were randomized; 127 received at least one infusion of sagopilone. Baseline demographic data were similar across all arms. Eight patients across all arms had a confirmed partial response; the primary endpoint was not achieved. The most frequently reported adverse event (AE) was peripheral sensory neuropathy (75%). Most hematologic AEs were grade 1 or 2. Conclusion: As fewer than five patients per arm responded after six treatment courses, the primary endpoint was not met. Sagopilone was only moderately tolerated. Most AEs, including peripheral neuropathy, were grade 1 or 2; hematologic toxicities were rare. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this retrospective study is to present data on patient characteristics, treatment patterns, and treatment results in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED). Patients and methods: From June 2004 to December 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed lung cancer. 397 patients were found having SCLC. We collected data on patient characteristics, chemotherapy, side effects, response on treatment and survival. Results: 39% of all patients had LD SCLC. Median age was 63 years. The response rate (RR) reached 76%. Stable disease was the result of first line therapy in 16%. Consecutive thoracic radiotherapy was given in 72%. Additional prophylactic cranial irradiation (PCI) was administered to 33%. 43% received second line therapy. Median survival was 18.8 months. In 61% of cases, ED SCLC was diagnosed. Median age was 61 years. Main metastatic sites were liver, bone, brain and adrenal glands. RR was 69%. Stable disease and progressive disease were the result of first line chemotherapy both in 12%. 15% received palliative cranial irradiation, 3% PCI. 51% were treated with second line therapy. Median survival reached 10.6 months. Conclusion: We provide a comprehensive analysis of a contemporary patient population. Treatment patterns and survival data fit well in the context of current international trials on more selected patients. Multivariate analyses confirmed extend of disease, performance status and LDH serum levels as independent prognostic factors for survival. Age and gender reached no statistical significance. [Copyright &y& Elsevier]