Real-life effectiveness of erlotinib as second-line treatment of stage IIIB/IV squamous non-small cell lung cancer: Results of the PEPiTA observational study.

OBJECTIVES: Erlotinib, an inhibitor of tyrosine kinase activity of the epidermal growth factor receptor, is effective in non-small cell lung cancer (NSCLC). Data on erlotinib use in squamous NSCLC are limited. This observational study aimed at evaluating the efficacy and safety of second-line erlotinib in patients with stage IIIB/IV squamous NSCLC in a real-life setting. MATERIAL AND METHODS: Patients with predominantly squamous stage IIIB/IV NSCLC, who failed first-line platinum-based therapy, were recruited and followed-up for 12 months. Patients underwent visits each trimester. Data were derived from case report forms, and functional assessment of cancer therapy-lung (FACT-L) questionnaires. RESULTS: A total of 152 patients were enrolled; the majority were males (90%) and mean age was 67.7 years. All patients had squamous (97%) or predominantly squamous (3%) NSCLC, of stage IIIB (21%) or IV (79%). Median progression free survival (PFS) and overall survival were 3 and 5.8 months, respectively. Disease progression was observed in the majority of the patients, mostly due to progression of primary tumour and/or metastatic sites, and led to death in 91/107 of patients. Of the 107 deaths reported, none were due to erlotinib. FACT-L questionnaires were interpretable up to the first visit and were in line with PFS data, showing a relatively good quality of life up to Month 3 (mean total score=78.8). No new or unexpected safety issues were reported. CONCLUSIONS: The results of this real-life cohort study like those of previous phase III/IV subgroups study analyses indicate that erlotinib is a valuable option for second-line treatment of stage IIIB/IV squamous NSCLC.

Major changes in lung cancer over the last ten years in France: the KBP-CPHG studies.

The incidence of lung cancer has dramatically increased in ten years, being now the most commonly diagnosed cancer in males and the fourth most commonly diagnosed cancer in females. Considering social and scientific evolution, the aim of the present study conducted by the French College of General Hospital Respiratory Physicians (CPHG) was to compare patient and lung cancer characteristics at a ten-year interval. Two epidemiological studies, KBP-2000-CPHG and KBP-2010-CPHG, were conducted at a ten-year interval. These prospective multicentre studies included all patients ≥ 18 years of age with primary lung cancer diagnosed between 1st January and 31st December 2000 or 2010, and managed in the respiratory departments of one of the participating general hospitals. A standardised form was completed for each patient. A steering committee checked recruitment exhaustiveness. Respectively, in 2000 and 2010, 137 and 104 centres included 5667 and 7051 patients. Compared to 2000, patients in 2010 were significantly older (65.5 ± 11.3 vs. 64.3 ± 11.5 years, p < 0.0001), more frequently women (24.3% vs. 16.0%, p < 0.0001) and never-smokers (10.9% vs. 7.2%, p < 0.0001). In 2010, adenocarcinoma was the most common tumour (45.4%, vs. 29.0% in 2000, p < 0.0001). The adenocarcinoma rate increased irrespective of sex, age, or smoking status (relative risk [RR] before and after adjustment, RR = 2.07 [1.92-2.24], p < 0.0001 and 2.06 [1.90-2.23], p < 0.0001). In ten years, lung cancer characteristics have therefore changed: more women, more never-smokers, and more adenocarcinomas. The particular high increase in adenocarcinoma rate deserves further analysis.

High-risk patients following hospitalisation for an acute exacerbation of COPD.

The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60-80 years and ≥80 years versus <60 years, relative risk 2.99, 95% CI 2.31-3.89), lower body mass index (25-30 kg·m(-2) versus ≤20 kg·m(-2), relative risk 0.80, 95% CI 0.66-0.97), lung cancer (relative risk 2.08, 95% CI 1.43-3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16-1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44-2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01-1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44-2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79-2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death.

Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).

BACKGROUND: Lung cancer has the highest mortality-rate per cancer, with an overall 5-year survival <15%. Several non-randomized studies pointed out the high sensitivity of low dose computed tomography (LDCT) to detect early stage lung cancer. In France, Depiscan, a pilot RCT of LDCT versus chest X-ray (CXR), started on October 2002 to determine the feasibility of enrollment by general practitioners (GPs), investigations and diagnostic procedures by university hospital radiologists and multidisciplinary teams, data management by centralized clinical research assistants, and anticipate the future management of a large national trial. METHODS: GPs and occupational physicians (OPs) selected and enrolled 1000 subjects in 1 year. Eligible subjects were asymptomatic males or females aged 50-75 years with a current or former cigarette smoking history of >/=15 cigarettes per day for at least 20 years (former smokers having quit <15 years prior to enrollment). Based to randomization, annual LDCT or CXR screenings were planned at baseline and annually for 2 years. RESULTS: Between October 2002 and December 2004, 765 subjects were enrolled by 89 out of the 232 participating GPs and OPs. Complete clinical and imaging baseline data were available for 621 individuals out of the 765 enrolled, due to 144 noncompliant subjects who withdrew their consent. At least one nodule was detected in 152 out of 336 subjects (45.2%) in the LDCT screening, versus 21 out of 285 subjects (7.4%) in the CXR screening arm. Eight lung cancers were detected in the LDCT arm and one in the CXR arm. DISCUSSION: This pilot trial allows estimating that non-calcified nodules are 10 [6.36-17.07] times more often detected from LDCT than from CXR. However enrollment by GPs was more difficult than expected with 41% active investigators and a high rate (19%) of noncompliant patients. This experience speaks to the need for a high level of GPs formation and a large, coordinated clinical research team in such a trial. TRIAL REGISTRATION NUMBER: 02526.

4-year mortality in patients with non-small-cell lung cancer: development and validation of a prognostic index.

BACKGROUND: Lung cancer is the commonest cause of death due to cancer in the world. Non-small-cell lung carcinoma (NSCLC) represents about 80% of overall lung cancer cases worldwide. An accurate predictive model of mortality in patients with NSCLC could be useful to clinicians, policy makers, and researchers involved in risk stratification. The objective of this study was to develop and validate a simple prognostic index for 4-year mortality in patients with NSCLC by use of information obtained at the time of lung cancer diagnosis. METHODS: In 2000, 4669 patients with histologically or cytologically proven NSCLC were enrolled prospectively from 137 pneumology departments in French general hospitals. Patients not lost to follow-up (n=4479) were randomly assigned to the development cohort (n=2979) or the validation cohort (n=1500). Every patient's physician completed a standard and anonymous questionnaire. We used a Cox model to identify variables independently associated with mortality and weighted the variables to create a prognostic index. FINDINGS: Median follow-up for survivors was 49 months (IQR 46-51). There were 2585 deaths (87%) in the development cohort and 1310 deaths (87%) in the validation cohort. Five independent predictors of mortality were identified: age (>70 years, 1 point); sex (male, 1 point); performance status at diagnosis (reduced activity, 3 points; active >50%, 5 points; inactive >50%, 8 points; and total incapacity, 10 points); histological type (large-cell carcinoma, 2 points); and tumour-node-metastasis (TNM) staging system (IIA or IIB, 3 points; IIIA or IIIB, 6 points; and IV, 8 points). The minimum and maximum possible point scores were 0 and 22, respectively. Scores of the prognostic index were strongly associated with 4-year mortality in the development cohort: 0-1 points predicted a 35% (95% CI 28-43) risk, 2-4 points a 59% (52-66) risk, 5-7 points a 77% (72-81) risk, 8-10 points an 88% (85-90) risk, 11-14 points a 97% (96-98) risk, and 15-22 points a 99% (97-100) risk. The corresponding percentages in the validation cohort were 36% (24-47), 60% (50-70), 77% (71-83), 89% (86-93), 96% (95-98), and 99% (98-100), respectively. The prognostic index showed good discrimination, with mean bootstrap c statistics of 0.85 (95% CI 0.84-0.86) in the development cohort and 0.86 (95% CI 0.85-0.87) in the validation cohort. INTERPRETATION: This prognostic index, incorporating personal, tumour, and functional information would be helpful in guiding patient management, resource use, and the design of clinical trials.

Lung cancer among women in France. Analysis of the 904 French women with lung cancer included in the KBP-2000-CPHG study of the French College of General Hospital-based Pneumologists (CPHG).

As the incidence of primary lung cancer in women seems to be increasing in parallel with that of smoking, we conducted an exhaustive epidemiological study in 137 hospitals in 2000. We identified 904 women with proven primary lung cancer (mean age 63.9 years), many of whom have never smoked (32.3%), particularly in cases of adenocarcinoma (43.4%). Small cell cancer accounted for 16.1% of cases. Adenocarcinomas were the most frequent (45.3%) of the non-small cell lung cancer (NSCLC), followed by squamous cell (23.4%), large cell (11.6%) and bronchoalveolar (1.9%) carcinomas. About one third (32.2%) of NSCLC were stage III and 48.1% were stage IV. Over half of all adenocarcinomas were stage IV. According to multivariate analysis, adenocarcinoma is related to less smoking and younger age. In conclusion, many women affected by lung cancer have never smoked. Adenocarcinoma appears to be the most frequent form and more often at a metastatic stage.

Direct treatment costs for patients with lung cancer from first recurrence to death in france.

OBJECTIVE: To determine the direct treatment cost of lung cancer management from progression to death from the viewpoint of the hospital. METHODS: A retrospective descriptive study was performed. Data from 100 patients who died of lung cancer and who had received treatment from four different types of hospital were used; the hospitals were public hospitals (teaching and non-teaching), private not-for-profit cancer centres, and private hospitals. Resource utilisation/cost data collected included the cost of diagnosis of the recurrence, the cost of hospitalisations or day care treatments and ambulatory surgery. All resources were valued in 2001 euros. RESULTS: In France, the average cost per patient was euro12 518 for the whole group (78% with non-small cell lung cancer [NSCLC], and 22% with small cell lung cancer [SCLC]), euro13 969 for patients with NSCLC and euro7369 for patients with SCLC. The higher cost of treatment in patients with NSCLC is explained by longer survival and duration of chemotherapy. In patients with NSCLC, 51% of the total cost corresponded to terminal care, with up to seven lines of chemotherapy. In patients with SCLC, the costs of diagnosis and terminal care each represented 41% of the total cost. CONCLUSIONS: The cost of treatment of recurrence of lung carcinoma is high, and is related to the number of lines of chemotherapy and the use of radiotherapy and surgery.

Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.