No abstract

The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.

Purpose ARCHER 1050, a randomized, open-label, phase III study of dacomitinib versus gefitinib in treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) and activating mutations in EGFR, reported significant improvement in progression-free survival with dacomitinib. The mature overall survival (OS) analysis for the intention-to-treat population is presented here. Patients and Methods In this multinational, multicenter study, patients age 18 years or older (≥ 20 years in Japan and Korea) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR (exon 19 deletion or exon 21 L858R) were enrolled and randomly assigned in a 1:1 manner to dacomitinib (n = 227) or gefitinib (n = 225). Random assignment was stratified by race (Japanese, Chinese, other East Asian, or non-Asian) and EGFR mutation type. The final OS analysis was conducted with a data cutoff date of February 17, 2017; at that time 220 deaths (48.7%) were observed. Results During a median follow-up time of 31.3 months, 103 (45.4%) and 117 (52.0%) deaths occurred in the dacomitinib and gefitinib arms, respectively. The estimated hazard ratio for OS was 0.760 (95% CI, 0.582 to 0.993; two-sided P = .044). The median OS was 34.1 months with dacomitinib versus 26.8 months with gefitinib. The OS probabilities at 30 months were 56.2% and 46.3% with dacomitinib and gefitinib, respectively. Preliminary subgroup analyses for OS that are based on baseline characteristics were consistent with the primary OS analysis. Conclusion In patients with advanced NSCLC and EGFR activating mutations, dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (TKI) to show significant improvement in OS in a phase III randomized study compared with a standard-of-care TKI. Dacomitinib should be considered one of the standard treatment options for these patients.

Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

BackgroundThis is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib.Patients and methodsALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS).ResultsAltogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9–12.2] with alectinib and 1.4 months (95% CI: 1.3–1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08–0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17–0.59); median PFS was 7.1 months (95% CI: 6.3–10.8) with alectinib and 1.6 months (95% CI: 1.3–4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks).ConclusionAlectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.Trial registrationClinicalTrials.gov NCT02604342; Roche study MO29750

Bone metastasis in lung cancerLung cancer is the third most common form of cancer to spread to bone. About 30-40% of patients with lung cancer developed bone metastases during the course of their disease; the median survival time of patients with this secondary lesion is 7 months [Coleman, 2001]. These metastases are associated with significant morbidity, loss of functional independence and reduction in quality of life (QOL) [Berenson et al. 2006]. Bone metastasis accounts for 350,000 cancer patients deaths each year [Mundy, 2002] and in lung cancer is associated with increased social costs due to medical care, hospitalization days and cost of treatment [Botteman et al. 2007].In a retrospective study of 259 nonsmall cell lung cancer (NSCLC) patients, the most common site of skeletal metastases was the spine in 50% of patients, followed by the ribs (27.1%), ilium (10%), sacrum (7.1%), femur (5.7%) and humerus, scapula and sternum (2.9%) [Tsuya et al. 2007]. The prognosis was worse in patients with metastasis to the appendicular bone than in patients with metastases only on an axial bone [Sugiura et al. 2008].Pain is usually the first symptom of lung cancer with bone metastases in 80% of patients [Kosteva and Langer, 2008]. Patients with osseous metastases complain of pain at some point with wide variation in pattern and severity [Delaney et al. 2008]. Many factors are implicated in the pain of osseous metastases but a significant portion of the pain seems to be related to osteoclastic bone resorption. Bone and brain metastasis in lung cancer: recent advances in therapeutic strategiesChiara D'Antonio, Antonio Passaro, Bruno Gori, Ester Del Signore, Maria Rita Migliorino, Serena Ricciardi, Alberto Fulvi and Filippo de Marinis Abstract: Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is ...

Background Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. Materials and Methods Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. Results A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre‐existing AIDs were not significantly related with progression‐free survival and overall survival. Conclusion This study quantifies the increased risk of developing irAEs in patients with pre‐existing AIDs who had to be treated with anti‐PD‐1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the “hot topics” in gender‐related differences in immuno‐oncology. Implications for Practice Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune‐related adverse events (irAEs) in patients with pre‐existing AIDs who had to be treated with anti‐programmed death‐1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre‐existing autoimmune disease.

No abstract