Real world data of efficacy and safety of erlotinib as first-line TKI treatment in EGFR mutation-positive advanced non-small cell lung cancer: Results from the EGFR-2013-CPHG study.

BACKGROUND: Phase III clinical trials have demonstrated the merits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. Using a cohort of unselected patients treated with erlotinib, we sought to further describe patient and tumour characteristics, and to evaluate their progression-free survival (PFS) and overall survival (OS). METHODS: Overall, 44 pulmonologists included patients with the required characteristics as follows: Stage IIIB-IV NSCLC, EGFR-activating mutation, age≥18 years, and having to start erlotinib therapy or receiving erlotinib therapy as the first-line TKI, regardless of treatment-line. The analyses were performed using R software, with survival rates calculated according to the Kaplan-Meier method. RESULTS: A total of 177 patients, aged 72 years on average, were enrolled over a 2-year period. The cohort included 123 women (69.5%), 158 Caucasians (89.3%), 112 non-smokers (63.2%), and 167 adenocarcinomas (94.3%), at either stage IIIB (21) or IV (156), with a good performance status (PS 0-1, 127). Overall, 40 exhibited brain metastases at baseline (22.6%), while 75 had undergone earlier treatment (42.4%). Median PFS was 11.7 months and OS 25.8 months, with respectively a 1-year rate of 48.6% and 74%. The risk of death correlated with ECOG status (PS=2, HR=4.48, P<0.001) but not with brain metastasis (HR=1.67, P=0.278). CONCLUSIONS: This study has confirmed erlotinib's efficacy and safety for unselected patients, with PFS and OS comparable to those obtained in phase III trials.

PTEN, ATM, IDH1 mutations and MAPK pathway activation as modulators of PFS and OS in patients treated by first line EGFR TKI, an ancillary study of the French Cooperative Thoracic Intergroup (IFCT) Biomarkers France project.

OBJECTIVES: Tumor mutation screening is standard of care for patients with stage IV NSCLC. Since a couple of years, widespread NGS approaches used in routine diagnostics to detect driver mutations such as EGFR, KRAS, BRAF or MET allows the identification of other alterations that could modulated the intensity or duration of response to targeted therapies. The prevalence of co-occurring alterations that could affect response or prognosis as not been largely analyzed in clinical settings and large cohorts of patients. Thanks to the IFCT program "Biomarkers France", a collection of samples and data at a nation-wide level was available to test the impact of co-mutations on first line EGFR TKI in patients with EGFR mutated cancers. MATERIALS AND METHODS: Targeted NGS was assessed on available (n = 208) samples using the Ion AmpliSeq™ Cancer Hotspot Panel v2 to screen for mutations in 50 different cancer genes. RESULTS: This study showed that PTEN inactivating mutations, ATM alterations, IDH1 mutations and complex EGFR mutations were predictors of short PFS in patients with a stage 4 lung adenocarcinoma receiving first line EGFR TKI and that PTEN, ATM, IDH1 and KRAS mutations as well as alterations in the MAPK pathway were related to shorter OS. CONCLUSION: These findings may lead to new treatment options in patients with unfavorable genotypes to optimize first line responses.

[One-year survival improvement in lung cancer in France. Results of the prospective real life studies KBP-2000-CPHG and KBP-2010-CPHG]. / Amélioration de la survie à 1 an dans le cancer du poumon en France. Résultats des études prospectives en vie réelle, KBP-2000-CPHG et KBP-2010-CPHG.

INTRODUCTION: The French college of general hospital respiratory physicians (CPHG) has conducted 10 years apart two prospective observational studies to assess changes in the primary lung cancer epidemiology and outcomes, including 1-year mortality. METHODS: In 2000 and 2010, all volunteer adult patients followed in the respiratory department of general hospitals participating in the study were consecutively included if their lung cancer was histologically or cytologically diagnosed between 01 January and 31 December (sample date). Their vital status at least 1 year after inclusion and date of death (if applicable) were collected. RESULTS: Respectively, 5667 and 7051 patients were included in the study in 2000 and 2010 and vital status of 5441 (96.0%) and 6981 (99%) patients known. One-year mortality rate was 61.8% in 2000 and 56.4% in 2010 (P<0.0001). Mortality rate significantly decreased from 2000 to 2010 in non-small-cell lung cancer (60.7% vs. 55.2%; P<0.0001) but not in small-cell lung cancer (66.9% vs. 64.2%; P=0.22). The year of diagnosis was an independent risk factor of mortality (OR=0.84; 95% CI: 0.77-0.91; P<0.0001). CONCLUSION: Although it remains low (43.6% in 2010), life expectancy at 1 year for patients with lung cancer has improved in 10 years. Five-year results are expected to show whether this improvement is maintained or not over time.

[Epidemiology, management and cost of bone metastases from lung cancer]. / Épidémiologie, prise en charge et coût des métastases osseuses des cancers bronchopulmonaires (hors métastases rachidiennes).

UNLABELLED: In lung cancer, there is a significant incidence of bone metastases with skeletal complications affecting more than 50% of patients. The systematic detection of bone metastases should be included in the initial staging of lung cancer in order to begin their management at an early stage. Treatment is either pharmacological (analgesics, zoledronic acid, anti-rank ligand) or non-pharmacological (radiotherapy, interventional radiological techniques, surgery) especially when bone metastases become symptomatic or complicated. External beam radiation, used for both analgesia and strengthening, can be combined with percutaneous and surgical treatments. Prophylactic or restorative surgery for pathological fractures should be subject to multidisciplinary discussion. Finally, the medico-economic impact of bone metastases is substantial. This is related to treatment of bone complications, which emphasises the importance of their prevention. CONCLUSION: Bone metastases from lung cancer cause complications which impact on patients' quality of life. Their management should be by a multidisciplinary approach in view of the numerous therapeutic options.

[Carcinomatous lymphangitis]. / Lymphangite carcinomateuse.

DEFINITION: Carcinomatous lymphangitis is a radioclinical entity accounting for about 8% of all cases of lung metastasis defined as the presence of tumoral cells in lymph vessels and lung interstitium. DIAGNOSIS: Biopsy specimens or bronchial brushings obtained by fibroendoscopy or bronchioalveolar lavage fluid usually reveal adenocarcinoma. PRACTICAL MANAGEMENT: In clinical practice, the patient presents with dyspnea and non-specific infiltration on the chest x-ray. The clinical situation worsens rapidly. Millimetric CT-scan shows highly suggestive polygonal images in the subpleural area. Respiratory function tests may be helpful for the differential diagnosis, particularly in difficult cases, showing a mixed ventilation disorder without altered carbon monoxide diffusion and hypoxemia at rest without hypercapnia. SEARCH FOR THE PRIMARY CANCER: Primary lesions must be identified for specific treatment. Pathology findings help guide the search. Despite the highly unfavorable prognosis (median survival = 3 months), etiological treatment when possible can improve quality of life and possibly survival. Symptomatic treatment is indicated and must be adapted to each individual case.