Nathalie Baize

Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study

PURPOSE Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. PATIENTS AND METHODS In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. RESULTS Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). CONCLUSION In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.

Feasibility and clinical impact of re-biopsy in advanced non small-cell lung cancer: A prospective multicenter study in a real-world setting (GFPC study 12-01)

OBJECTIVES When advanced non-small-cell lung cancer (NSCLC) progresses during first-line treatment, re-biopsy may be indicated to detect a possible new biological profile (comparison to initial status, emergence of resistance biomarkers, or assessment of new biomarkers). The aim of this pragmatic prospective multicenter study was to assess the feasibility and clinical utility of re-biopsy in advanced NSCLC in a real-world setting. METHODS The main inclusion criteria were advanced NSCLC with an indication for repeat biopsy identified by the patients clinician. The primary outcome was the percentage of successful procedures. Secondary outcomes were the type of procedure, new biological status, tolerability of the procedure, and clinical utility (treatment modification). RESULTS From May 2012 to May 2013, 18 centers enrolled 100 patients (males: 44%; median age: 64.8 years; PS 0/1: 88%; adenocarcinoma: 89%; EGFR mutated: 50%; no initial biological profile: 16.4%). Re-biopsy was not possible in 19.5% of cases and provided no or too few tumor cells in 25.6% of cases. Repeat biopsy was useful for guiding treatment in 30.4% (25/82) of cases. Complications were infrequent (2 cases of moderate bleeding and 1 case of pneumothorax). CONCLUSION Re-biopsy of advanced NSCLC is feasible in the real-world setting, with acceptable adverse events. Guidelines are needed on the indications of re-biopsy, the choice of procedure, the sampling site, and laboratory analysis.

Interim analysis of the Spanish Lung Cancer Group (SLCG) BRCA1-RAP80 Expression Customization (BREC) randomized phase III trial of customized therapy in advanced non-small cell lung cancer (NSCLC) patients (p) (NCT00617656/GECP-BREC).

LBA8002 Background: Findings from the SLCG phase II customized chemotherapy trial (NCT00883480) showed that RAP80, a component of the BRCA1 complex, influenced outcome both in p with low BRCA1 expression treated with cisplatin (cis)/gemcitabine (gem) and in p with intermediate/high BRCA1 levels treated with cis/docetaxel (doc) or with doc alone. Together with the French Lung Cancer Group, the SLCG has performed a prospective, randomized phase III trial comparing noncustomized cis/doc with customized therapy in metastatic NSCLC p. A parallel phase II study (ChiCTR-TRC-12001860) is being carried out in China under the auspices of the SLCG. METHODS Since 6 March 2008, 391 p with wild-type EGFR have been randomized 1:1 to the control or experimental arm. p in the control arm receive cis/doc; p in the experimental arm receive treatment according to their BRCA1 and RAP80 levels: p with low RAP80, regardless of BRCA1 levels, cis/gem; p with intermediate/high RAP80 and low/intermediate BRCA1, cis/doc; p with intermediate/high RAP80 and high BRCA1, doc alone. The primary endpoint is progression-free survival (PFS). RESULTS At the planned interim analysis (cut-off, 15 October 2012; N=279), PFS was 5.49 months (m) in the control and 4.38 m in the experimental arm (P=0.07). Overall survival (OS) was 12.66 m in the control and 8.52 m in the experimental arm (P=0.006). Response rate (RR) was 37.3% in the control and 27% in the experimental arm (P=0.07). In the multivariate analysis including PS, treatment arm, BRCA1, RAP80, histology, smoking status, and metastatic site, only extrathoracic metastases were associated with an increased risk of progression (HR, 1.78; P=0.02). CONCLUSIONS Based on the negative results for PFS at the interim analysis, accrual has been closed on this study. Negative results may be due to the poor predictive capacity of RAP80 and the inclusion of doc alone as a treatment in the experimental arm. In addition, doc/cis may not be the ideal combination for the control arm. CLINICAL TRIAL INFORMATION NCT00617656.

Assessment of palliative care for advanced non-small-cell lung cancer in France: A prospective observational multicenter study (GFPC 0804 study)

INTRODUCTION Few studies assessed, in real life, symptoms, specific interventions and factors influencing palliative care (PC) initiation for patients with advanced non-small-cell lung cancer (NSCLC). The objective of this study was to examine, in a prospective cohort of advanced NSCLC patients, PC use and factors associated with early (≤3 months after diagnosis) PC initiation. METHODS It was an observational multicenter study. Each center included 10 consecutive patients with PC initiation. RESULTS 514 patients were enrolled by 39 centers (age: 62.3 ± 10.7 years, performance status: 0/1; 68.6% cases). At baseline, the most frequent symptoms concerned pain (43.6%), malnutrition (37%) and psychological disorders (25.3%). Specific interventions were infrequent for pain control and malnutrition, but were more numerous for psychological and social problems and terminal care. Median time between diagnosis and PC initiation was 35 [13-84] days, median PC duration was 4.2 [0.6-9.3] months. Median overall survival was 8.6 [6.6-10.7] months; median survival after PC initiation was 3.6 [3.2-4.5] months. In multivariate analysis, only PS ≥2 was linked to early PC. CONCLUSION This study showed that early PC initiation is not a standard for patients with advanced NSCLC.

Second-line treatments of small-cell lung cancers.

ABSTRACT Introduction: Second-line therapies for relapsed small cell lung cancer (SCLC) patients remain a challenge, with limited clinical benefit because of rapid tumor growth, early dissemination and the development of drug resistance during the disease. Recent developments in genomic sequencing have provided further insight into the biology of the disease, identifying new targets and new pathways. Areas covered: This review details chemotherapy, targeted therapies and immune-checkpoint blockades that have been investigated as second-line treatments for SCLC patients using a PubMed search (period 1990 – 2016, terms used: SCLC, treatments, second line, therapy). Expert commentary: Recent genomic, proteomic and preclinical studies have identified novel therapeutic strategies currently being evaluated in clinical trials. Promising approaches for SCLC management include delta-like ligand-3 (DLL3)-targeted antibody–drug conjugate, combination targeted therapies, or targeted therapy–chemotherapy with an additive effect superior to the efficacy of single agents. The blockade of immune checkpoints has yielded promising preliminary results and is being investigated in ongoing trials. The inclusion of SCLC patients relapsing after platin-doublet induction in well-designed clinical trials remains a major challenge.

Association between lung cancer somatic mutations and occupational exposure in never-smokers.

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure. BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations. Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency. Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations. Asbestos exposure is associated with a lower rate of EGFR mutation in lung cancer of never-smokers http://ow.ly/wFUY30fkbcz

Second-Line Oral Chemotherapy (Lomustine, Cyclophosphamide, Etoposide) Versus Intravenous Therapy (Cyclophosphamide, Doxorubicin, and Vincristine) in Patients With Relapsed Small Cell Lung Cancer: A Randomized Phase II Study of GFPC 0501

BACKGROUND No reference second-line treatment of small-cell lung cancer is available. The aim of the present phase II randomized trial (Groupe Français de Pneumo-Cancérologie 0501) was to compare, in patients with progressive small-cell lung cancer after first-line platinum-based chemotherapy, oral multidrug chemotherapy (lomustine, cyclophosphamide, etoposide) and intravenous therapy with cyclophosphamide, doxorubicin, and vincristine (CAV) in terms of efficacy and tolerance. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, response rate, and tolerance. PATIENTS AND METHODS The study randomized 131 patients (76.7% male; median age, 61 ± 8.1 years, 85.5% with a performance status of 0-1), 65 to oral therapy and 66 to the CAV arm. No statistically significant differences were found in the baseline patient characteristics. RESULTS The OS and PFS was 6.1 and 3 months for the oral arm and 5.8 and 3.1 months for the CAV arm, respectively. The control disease rate was 61.6% and 45.5% in oral and CAV arms, respectively. No unexpected adverse events occurred, and no statistically significant difference was found between the 2 arms in terms of toxicity (grade 4 hematologic adverse events in 32.3% and 31.8% of patients in the oral and CAV arms, respectively). CONCLUSION Compared with CAV, oral therapy in this setting appears as feasible as, but not superior to, the efficacy in the CAV arm.

1287PRETROSPECTIVE MULTICENTER STUDY IN NON SMALL CELL LUNG CANCER (NSCLC) PATIENTS WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) ACTIVATING MUTATION TREATED FIRST-LINE TYROSINE KINASE INHIBITOR (TKI): EVALUATION OF PROGRESSION ACCORDING TO RECIST, THERAPEUTIC APPROACH AND ITS EFFECT

ABSTRACT Aim: Background: EGFR-TKI are a standard treatment for patients (pts) with NSCLC harboring activating EGFR mutations. All pts develop acquired resistance. At progression, the standard treatment is chemotherapy. Retrospective studies suggest that continuous use of EGFR-TKI beyond progressive disease (PD) may benefit some pts. Objective: The purpose of our retrospective multicentric study is to determine the frequency of continuation of EGFR-TKIs beyond RECIST-PD, and investigate the association of pts and disease characteristics with continuation of EGFR-TKIs at progression. Methods: Main inclusion criteria were: pts with NSCLC and activating EGFR mutations, EGFR-TKIs as their initial systemic therapy received between January 2010 and July 2012, Measurable lesion according to RECIST 1.1, acquired resistance to EGFR-TKI according to Jackmans criteria. Following data were collected: demographic and clinical data, Progression free survival (PFS), Overall Survival (OS), mutational status, mode of progression, therapeutic approach at PD. A comparison of clinical data and outcome of pts receiving EGFR-TKI beyond PD (group 1) versus discontinuing EGFR-TKI at PD (group 2) was made. Results: 133 pts were recruited in 29 centers: age 69 ± 12.7 years, female 67.6%, EGFR mutation exon 19/21/others: 65.4 %/ 30.8%/ 3.8%, adenocarcinoma 98%, never smokers 68.5%, PS 0/1: 80,5%. First line treatment: gefitinib 77.4%, erlotinib 21.8%. 40.6% pts continued EGFR-TKI beyond RECIST-PD (25,6% EGFR-TKI alone, 15% EGFR-TKI combined with local treatment). 59.3% pts changed treatment (39.8% chemotherapy, 7.5% combination chemotherapy +EGFR-TKI, 12% BSC). Median PFS was 9,4 (CI95% :8-10,9) months and median OS was 21,6 (CI95%18,7-25,8) months in the entire population. In group 1 and 2, m PFS was 10,1 (CI95% :7,7-12,3) and 8,7 (CI 95% :7,5-10,9) (p = 0,34) months and m OS was 23 and 20,4 months respectively (p = 0,08). All comparative data between groups 1 and 2, univariate and mutivariate analysis will be presented. Conclusions: This large retrospective study confirms that, in some circumstances, continuous use of EGFR-TKI beyond PD does not hamper OS and should be considered.Prospective studies will help to determine which patients benefit more this strategy. Clinical trial information: Supported by an academic grant from boehringer ingelheim, Hoffman Roche. Disclosure: J.B. Auliac: In the last five years, JB Auliac has received honoraria for attending scientific meetings, speaking, organizing research or consulting, from Boehringer Ingelheim, Hoffman-Roche, Lilly and Pfizer; C. Decroisette Phan van Ho: consultancy Hoffman roche; S. Bota Ouchlif: travel/accomodation meeting: Lilly; R. Corre: board membership: roche, lilly consultancy: roche, lilly travel/accommodations meeting: lilly, roche; P. Fournel: consultancy: roche, lilly, boehringer ingelheim; A. Vergnenegre: consultancy: roche grants/grants pending:roche, lilly, boehringer; L. Greillier: consultancy: roche, lilly grants/grants pending: roche travel/accommodation meeting: lilly, roche; R. Gervais: consultancy: Roche, Astra Zeneca et Boehringer ingelheim. All other authors have declared no conflicts of interest.