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In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available. Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins. The Epidemio-Strategy and Medical Economics advanced and metastatic lung cancer data platform including advanced/metastatic nsqNSCLC patients from January 2015 was analyzed (cut-off date: June 30, 2020). Characteristics, epidermal growth factor receptor (EGFR) mutation and other mutations, treatment patterns, and clinical outcomes were assessed for patients harboring EGFR exon 20ins, common EGFR mutations, other EGFR mutations, and wild-type EGFR. Survival parameters were estimated by the Kaplan-Meier method in these four groups. Out of 9435 nsqNSCLC patients tested for EGFR, 1549 (16.4%) had a mutation, including 61 with EGFR exon 20ins (3.9% of all mutated EGFR). These 61 patients had a mean age of 63.6 years, were mostly female (68.9%) and non-smokers (55.7%), with de novo stage IV disease (73.8%) and performance status 0–1 (76.9%). Almost all patients (95.1%) with exon 20ins received systemic therapy (median, three lines). First-line systemic treatments consisted mainly of combination chemotherapy (70.7%), single-agent EGFR tyrosine kinase inhibitors (10.3%), and single-agent immunotherapy (5.2%). After a median follow-up of 25.0 (95% confidence interval [CI] 22.3–32.4) months, the median real-world overall survival was 24.3 (19.1–32.6) months in patients with exon 20ins compared to 35.4 (95% CI 32.6–37.5) in patients with common EGFR mutation (n = 1049) (p = 0.049) and 19.6 (95% CI 18.6–20.5) in patients with wild-type EGFR (n = 7866) (p = 0.2). This large national study in nsqNSCLC patients confirms that EGFR exon 20ins is a rare condition (0.6%). The prognosis associated with exon 20ins appears to be in line with that of wild-type EGFR, but worse than common EGFR mutations, highlighting the need for advancements for this rare population.

Purpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC. Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed. Results: Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received. Conclusions: These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.

Background The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores. Methods Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 “candidate cancer” genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a “matched therapy” and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES). Results Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68–75%). Only 94/550 patients (17%, 95%CI 14–21) received an “AGA-matched therapy” on progression. The most frequent AGAs leading to “matched therapy” included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such “matched therapy” improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of “matched therapy” was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with “matched therapy,” and 6-month overall survival (OS) was 62% (95%CI 52–73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH. Conclusions Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a “matched therapy” in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results. Trial registration ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158.

Background Antiangiogenic agents have improved the prognosis of non-squamous non-small-cell lung cancers (NSCLCs), even though all the patients are not eligible to receive them because of counterindications linked to the tumor's characteristics or comorbidities. Much less information is available about the eligibility of patients with squamous non-small-cell lung cancers (SQ-NSCLCs) to receive antivascular endothelial growth-factor (VEGF) treatments, even though such molecules are being developed for this histology. This study was undertaken to determine the percentage of advanced SQ-NSCLC patients who would be eligible to receive an antiVEGF agent as second-line systemic therapy. Methods This observational, multicenter, prospective study evaluated advanced SQ-NSCLC patients' criteria for ineligibility to receive an antiVEGF during a multidisciplinary meeting to choose their standard second-line systemic therapy. Results Among the 317 patients included, 53.6% had at least one ineligibility criterion, and ~20% had at least two, with disease extension to large vessels (39.8%), tumor cavitation (20.5%), cardiovascular disease (11%) and/or hemoptysis (7.2%) being the most frequent. Patients with an ECOG performance score of 1/2 had more cardiovascular contraindications that those with scores of 0. Conclusion Almost half of the SQ-NSCLC patients included in this study would have been eligible to receive an antiVEGF agent. The development of these molecules for these indications should be encouraged.

Background: The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. Methods: This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. Results: The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p Conclusion: The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.

The landscape for medical treatment of lung cancer has irreversibly changed since the development of immuno-oncology (IO). Yet, while immune checkpoint blockade (ICB) revealed that T lymphocytes play a major role in lung cancer, the precise dynamic of innate and adaptive immune cells induced by anticancer treatments including chemotherapy, targeted therapy, and/or ICB is poorly understood. In lung cancer, studies evaluating specific immune cell populations as predictors of response to medical treatment are scarce, and knowledge is fragmented. Here, we review the different techniques allowing the detection of immune cells in the tumor and blood (multiplex immunohistochemistry and immunofluorescence, RNA-seq, DNA methylation pattern, mass cytometry, functional tests). In addition, we present data that consider different baseline immune cell populations as predictors of response to medical treatments of lung cancer. We also review the potential for assessing dynamic changes in cell populations during treatment as a biomarker. As powerful tools for immune cell detection and data analysis are available, clinicians and researchers could increase understanding of mechanisms of efficacy and resistance in addition to identifying new targets for IO by developing translational studies that decipher the role of different immune cell populations during lung cancer treatments.

Introduction Molecular profiling is considered a standard of care in advanced NSCLC. A comprehensive next-generation sequencing panel can discover somatic or germline BRCA1/2 mutations that are new druggable molecular alterations. However, the phenotypic and potential therapeutic relevance of BRCA1/2 mutation in NSCLC remains poorly defined. Methods From April 2014 to March 2017, 600 newly diagnosed, EGFR/ALK negative patients with advanced NSCLC were enrolled in the SAFIR02-Lung trial. Molecular profiling was done at study entry on archival tissue or frozen tissue collected from a new biopsy specimen before the third cycle of platinum-based chemotherapy. The prevalence of BRCA1/2 variants and its biological relevance were assessed. A homologous recombinant deficiency (HRD) score was based on the copy number variation data, and the germline status was determined by blood analysis. The BRCA Share database and the French CGG consortium were the references for the variant classification. Results Of 379 patients with a molecular profile discussed in a tumor molecular board, BRCA1/2 variants were identified in 20 patients (5.3%), including eight patients (2.1%) with a confirmed pathogenic BRCA mutation. Two patients (0.5%) harbored a germline BRCA2 mutation, and for six others, a somatic BRCA mutation was identified (1.6%). All were men and mainly smokers (88%). The overall response rate to chemotherapy was 13%. BRCA variants of unknown significance were detected in 12 patients (3.2%), achieving an 8.3% overall response rate with chemotherapy. One-third of tumors carrying pathogenic BRCA mutations or variants of unknown significance had biallelic inactivation and high HRD score. Overall survival of this cohort was 12.8 months. Conclusions Pathogenic BRCA1/2 mutations occur in 2.1% of patients with advanced NSCLC. The predictive role of BRCA mutation for making treatment decisions in NSCLC seems limited based on clinical response (low platinum sensitivity) and molecular features (discrepancy between biallelic inactivation and high HRD score).

Purpose: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR–tyrosine kinase inhibitor (TKI) with an antiestrogen may overcome resistance to EGFR-TKI. Patients and Methods: The IFCT-1003 LADIE trial was a 2 × 2 arms parallel open-label randomized phase II trial. EGFR-TKI–naïve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib + fulvestrant (G+F) in the EGFR-mutated group (EGFR+) or with erlotinib (E) versus erlotinib + fulvestrant (E+F) in the EGFR wild-type group (EGFR-WT). The primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR-WT and EGFR+ patients. Results: Overall, 204 patients (gefitinib 104 and G+F 100) and 175 patients (erlotinib 87 and E+F 88) were enrolled in the EGFR+ and EGFR-WT cohorts. In the EGFR+ cohort, the primary endpoint was reached, with 58% of the G+F group patients being nonprogressive at 9 months. Adding fulvestrant to gefitinib was not associated with improved PFS (9.9 vs 9.4 months) or overall survival (OS; 22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were nonprogressive at 3 months). Adding fulvestrant to erlotinib was not associated with improved outcome (PFS 1.8 vs 2.0 and OS 10.3 vs 7.3 months). No PFS difference was observed regarding estrogen receptor alpha expression. The tolerance was as expected with no treatment-related death. Conclusions: Adding fulvestrant to EGFR-TKI is feasible, but not associated with prolonged PFS regardless of EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in an unselected population.

9095 Background: Targeted therapies (TT) are approved in NSCLC based on a limited number of oncogenic drivers. Numerous additional TT can be matched to other molecular alterations found in comprehensive profiles. We investigated the effect of 8 TT compared to SoC as a maintenance strategy after chemotherapy in pts with metastatic NSCLC. Methods: In SAFIR02-LUNG trial (NCT: 02117167), open-label multicentric phase II randomized trials, PS 0-1 pts with ALK/EGFR WT NSCLC after a CR/PR/SD to 4 cycles of platinum-based chemotherapy were selected. All pts underwent a fresh biopsy, followed by targeted sequencing on 70 genes and SNP-array when > 30% cancer cells were present on HES slides. In case of genomic alteration (including KRAS, ERBB2, BRAF, BRCA mutations), pts were randomized 2:1 between 8 TT and SoC. TT allocation was decided during weekly national tumor board, based on predefined guidelines. The primary endpoint was Progression-Free Survival (PFS) and the secondary endpoint was Overall Survival (OS). Results: 999 patients were enrolled and 394 had a molecular alteration eligible for the study. Among the 175 randomized pts (between July 2014 and May 2019), 116 received TT (65 selumetinib, 18 vistusertib, 9 capivasertib, 8 AZD4547, 5 AZD8931, 5 vandetanib, 4 olaparib, 1 savolitinib) and 59 SoC (54 pemetrexed, 4 gemcitabine and 1 erlotinib). Median age was 60, 40.6% were female, 4.6% never-smoker, 44% were PS 0, 88.6% had a non-squamous NSCLC and 26.9% a PR to chemotherapy. At data cut-off, 168 pts had progressed or died. With a median follow-up of 42.0 months (mo), median PFS was 2.7 mo (95% confidence interval (CI) 1.6 to 2.7) with TT vs. 2.7 mo (95%CI 1.6-4.1) with SoC (HR for disease progression or death 1.00; 95%CI = 0.73 to 1.38; p = 0.978). There was no significant PFS differences among the molecular subgroups; in the cohort with KRAS or BRAF mutation without STK11 mutations the HR for disease progression or death was 0.76; 95%CI = 0.52 to 1.13; p = 0.17. Median OS was 14.3 mo (95%CI 11.0-18.3) with TT vs. 14.1 mo (95% CI 8.0-30.9) with SoC (HR for death 1.12; 95%CI = 0.75-1.65; p = 0.581). Grade 3 or 4 treatment-related adverse events occurred in 31 pts (26.7%) on TT (G3: 30 pts (25.9%), G4: 1 pt (0.8%)) and in 13 (22%) on SoC (G3 8 pts, G4 5 pts). Conclusions: The SAFIR02-LUNG trial demonstrated the feasibility of a routine precision medicine for advanced NSCLC. However, the monotherapy TT used as maintenance therapy after platinum-based chemotherapy failed to improve PFS or OS in this advanced ALK/EGFR WT NSCLC pts population. Newly available therapeutic options (ex. for KRASG12C, RET, NTRK, ERBB2, NRG1, etc) need to be evaluated. Clinical trial information: 2013-001653-27.

9062 Background: In Europe, 10-15% of non-squamous non-small cell lung cancer (nsqNSCLC) have EGFR mutations of which 5-12% are an Exon 20 insertion (20ins). Methods: Analysis of Epidemio-Strategy and Medical Economics (ESME) Advanced and Metastatic Lung cancer (AMLC) Data Platform (NCT03848052), a multicenter real-life database using a supervised, retrospective data collection process. The database includes 13737 advanced nsqNSCLC treated from January 2015 at participating centres. The cut-off date for patient follow-up for this analysis was June 30, 2020. The aim of the study was to assess real-world patient characteristics, treatment patterns and clinical outcomes of advanced nsqNSCLC EGFR 20ins. Overall survival (OS) of EGFR cohorts (20ins, 19del/L858R without 20ins, other EGFR mutations) and EGFR wild-type/not tested cohort were assessed. Results: 1549 (11.3%) nsqNSCLC had an EGFR mutation, 61 (3.9%) of whom being an EGFR 20ins. These 61 patients (pts) are mainly female (68.9%), non-smoker (55.7%), with de novo stage IIIB/IV disease (78.6%), PS 0-1 (76.9%). Median age was 68.0 years (q1-q3: 54-74). PD-L1 status was assessed in 34 (55.7%) pts, mainly (n = 20) before first line and 22 (64.7%) had negative result. Most (63.9%) pts had EGFR 20ins positive result available before first line. Almost all pts (95.1%, n = 58) received a systemic therapy with a median number of 3 (q1-q3: 1-4) lines. In first line setting, 74% of the pts received chemotherapy (mainly chemotherapy combination), 13.7% received EGFR TKI (mainly as monotherapy) and 8.6% received immunotherapy only. Median treatment duration for pts treated with CarboPem (n = 19), CisplatinPem (n = 16) and CarboTaxol (n = 6) were 4.7 (q1-q3: 2.6-6.6), 7.4 (q1-q3: 5.0-12.8) and 3.3 (q1-q3: 2.8-3.8) months, respectively. For afatinib (n = 3), erlotinib (n = 2) and gefitinib (n = 1), median treatment durations were 1.6 (q1-q3: 0.5-2.8); 1.8 (q1-q3: 1.4-2.1) and 2.3 months, respectively. After a median follow up of 36.3 (95%CI: 34.1-39.8) months, median OS was 24.3 (95%CI: 19.1-32.6) months; 1 and 2-years OS rates were 82.5% (95%CI: 69.7-90.2) and 52.6% (95%CI: 37.3-65.9), respectively. For pts with 19del/L858R without 20ins (n = 1049) and those with other EGFR mutations (n = 439) median OS were 35.4 (95%CI: 32.6-37.5) and 41.7 (95%CI: 31.9-53.5), respectively compared to 20.7 (95%CI: 20.0-21.8] months for pts EGFR wild type/not tested (n = 12188). Conclusions: This large, national real-world analysis based on medical chart data’s confirm that EGFR 20ins is a rare disease (0.4% of advanced nsqNSCLC). Currently available EGFR TKIs appear to have low efficacy and response to chemotherapy seems identical to that of EGFR wild-type/not tested pts. Prognosis for NSCLC pts with EGFR 20ins mutations was in line with that of EGFR wild type/not tested but worse than common EGFR mutations highlighting the need for advancements for this rare population.

9561 Background: Medical treatment of lung cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune biomarkers of efficacy are still lacking. Preliminary data in leukemia and pancreatic cancer showed that soluble immune checkpoints are associated with a reduced overall survival (OS). This led us to explore the prognostic and predictive value of soluble immune checkpoints in non-small cell lung cancer (NSCLC) patients treated with chemotherapy or ICI. Methods: We analyzed 90 advanced NSCLC patients. The pilot cohort (Rennes University Hospital, France), included 48 patients treated with platinum doublets (n = 33) or ICI (n = 15) (LOC/11-16 protocol). The confirmation cohort (Paoli-Calmettes Institute) included 42 patients treated with ICI (nivolumab or pembrolizumab) in a longitudinal prospective setting (Immunosup trial, NCT03595813). In both cohorts, enzyme-linked immunosorbent assays (ELISA) were performed in baseline plasma samples for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3-A1 and BTN2A1. Soluble ICI levels were linked to clinical data using Kaplan-Meier, log-rank and Cox proportional-hazards models. Cut-points were determined using maxstat package for survival, R software R 3.6.2. Results: Five soluble immune checkpoints correlated and clustered together in unsupervised analysis (PD-1, PD-L1, global BTN3, BTLA, BTN3-A1), but were not associated with ICI efficacy. In patients treated with ICI, in the pilot and confirmation cohort, a high baseline plasmatic concentration of soluble BTN2A1 was significantly associated with an improved OS (confirmation cohort with a BTN2A1 cut-point of 3.55 ng/ml: HR = 0.30, 95%CI = 0.12-0.74, p = 0.0057, median OS in BTN2A1low = 7.6 months and median OS in BTN2A1hi = 19.5 months). On the contrary, in patients treated with chemotherapy, soluble BTN2A1 concentration was not associated with overall survival. Conclusions: In advanced NSCLC patients, a high baseline plasmatic concentration of soluble BTN2A1 was correlated with improved outcomes for ICI, but not for chemotherapy, suggesting that baseline soluble BTN2A1 level is a potential predictive biomarker of ICI efficacy. Additional studies are ongoing to confirm this finding.

Background: Nivolumab is approved worldwide as second-line treatment for metastatic non-small cell lung cancer (NSCLC). Despite the fact that most of these cancers are being diagnosed in the older patients, few of the patients were included in pivotal trials. We aimed to describe efficacy and safety in a ``real-world'' older population. Patients and Methods: We retrospectively collected data from older patients (>= 70 years old) with advanced or metastatic NSCLC treated with Nivolumab in our institution. We analyzed safety (CTCAE v4.0 criteria), efficacy (clinical benefit rate, progression-free survival, and overall survival), and correlated these features to geriatric parameters and PD-L1 expression. Along with this cohort, we assessed safety at a national level by retrieving all cases of Nivolumab (prescribed for NSCLC) induced adverse events analyzed by the French pharmacovigilance network during the inclusion period. Results: From July 2015 to September 2016, 30 patients were enrolled with a median age of 752. Clinical benefit rate was 30.6%. Median progression-free survival and overall survival were 33 and 7.1 months, respectively. Fifteen patients (50%) presented an immune-related adverse event (IrAE) of any grade, including four high grade IrAEs. Two hundred and eighty IrAEs had been notified to the French pharmacovigilance network including 91 (35.2%) concerning older patients. Frequency and pattern of IrAEs were similar for older patients and younger subjects. Conclusions: Even though frequency and patterns of IrAEs are different from pivotal studies, these results don't seem specific to older patients. Further prospective investigations are needed to better characterize and predict the impact of Nivolumab on older patients with NSCLC. (C) 2018 Elsevier Ltd. All rights reserved.

Background/aim Radiological evaluation after stereotactic-body-radiotherapy (SBRT) for non-small-cell lung carcinoma (NSCLC) is often difficult due to lung radiation-induced image modifications on computed tomographic (CT) scan. The aim of this study was to evaluate positron-emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose after SBRT in primary lung cancer. Patients and methods Eighteen patients with histologically proven NSCLC were treated with SBRT. All had PET-CT evaluations before treatment, at 2 to 3 months and at 1 year post SBRT during the follow-up. Results Early PET-CT in 12/18 patients who did not experience local failure did not show any progression. No conclusion could be drawn in four cases because early PET-CT was disturbed by inflammatory reaction. Early PET-CT was not predictive of late outcome for two patients, as it showed a significant response followed by disease progression on late evaluation. Conclusion Early PET response appears to correlate with local control at 1 year post SBRT.

9079 Background: First-line treatment of metastatic EGFR-mutated NSCLC relies on EGFR-TKIs. However, all patients (pts) eventually develop progression. Dual inhibition of EGFR with afatinib (A), an irreversible pan-erbB TKI, and cetuximab (C), an EGFR monoclonal antibody, has shown activity in EGFR-mutated pts with acquired resistance to TKIs, regardless of the T790M status. Methods: We conducted a phase II randomized trial in advanced NSCLC pts harboring an activating EGFR mutation, who had not received prior therapy. Pts were treated with A (40 mg/d) until progression alone or with C 500 mg/m² every 2 weeks during 6 months (mos) (beginning at D15 at 250 mg/m²). Primary endpoint was time-to-treatment failure (TTF) at 9 mos for pts with del19 and L858R mutations. Secondary endpoints include safety, progression-free survival (PFS), overall survival (OS). Prospective monitoring of the T790M mutation was performed on circulating tumoral DNA (ctDNA) by digital PCR. Results: Trial was stopped early due to futility analysis after 118 pts were enrolled (59 in each arm). Baseline characteristics were balanced between the 2 arms, and especially for the types of EGFR mutation (del19, 55.9 vs 50.8%; L858R, 39 vs 40.7%; others, 5.1 vs 8.5% in AC and A arms, respectively). Treatment-related AEs of any grades were similar, although there was an excess of grade 3 AEs in the AC arm (50 vs 37.3%), but no of grade 5. The excess in grade 3-5 AEs was essentially due to cutaneous (96.6 vs 81.4%), eyes (32.8 vs 27.1%), hematological (22.4 vs 15.3%) but not to digestive toxicities (89.7 vs 98.3%). Among the 117 pts included in the efficacy analysis, 9-months TTF was 63.3% (47.5-75.6) in arm A and 65.8% (50.1-77.66) in arm AC. Median TTF was 11.1 mos (8.3-not reached [NR]) and 10.8 mos (9.2-13.7) in arms A and AC, respectively. Median PFS was 11.1 mos (8.3-NR) and 12.8 mos (9.2-13.7), respectively. Median OS was 20.8 mos (17.5-NR) and NR (17-NR), respectively. Conclusions: Efficacy of AC was similar to that of A alone. These results don’t support further evaluation of this combination in this setting. Results of ctDNA monitoring will be reported during the meeting. Clinical trial information: NCT02716311.

TPS9121 Background: New treatment strategies are needed for advanced NSCLC patients who progress on treatment with immune checkpoint inhibitors (ICI). Tedopi (OSE2101) is a neoepitope vaccine restricted to HLA-A2 positive patients (45%) targeting five tumor-associated antigens frequently expressed in lung cancer cells, ACE, HER2, MAGE2, MAGE3 and P53. Previously, in a phase II trial (Barve et al. JCO 2008), Tedopi showed a median overall survival (OS) of 17.3 months with a manageable safety profile in advanced NSCLC patients. ATALANTE-1 (NCT02654587) is a randomized, open-label, phase 3 study comparing the efficacy and safety of TEDOPI with standard of care (SoC) treatment in HLA-A2 positive patients with advanced NSCLC, as second- or third-line therapy. Methods: Patients with advanced NSCLC without EGFR-sensitizing mutations or ALK rearrangements; progressive disease to platinum-based chemotherapy (ChT) with sequential or concurrent ICI; HLA-A2 positivity (blood test); ECOG PS 0-1; with treated and asymptomatic brain metastases,, are randomized 2:1 to receive 5mg Tedopi subcutaneously Q3W for 6 cycles, then Q8W for the reminder of the year and finally Q12W, or SoC treatment with: docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W (in non-squamous and pemetrexed-naïve patients). Treatment continues until progression, intolerable toxicity or consent withdrawal, in both arms. Patients are stratified by histology, best response to first line, and line rank of ICI. Tumor assessment is performed every 6 weeks (RECIST 1.1). Primary endpoint is OS. Secondary end points are PFS, ORR, DCR, and duration of response, quality of life and safety. This is a superiority study with a hazard ratio of 0.7, two-sided alpha 5% and power 80%, after 278 events are observed. An independent analysis (1year OS rate) is planned in the first 84 patients treated with Tedopi. Last trial review by the DMC in June 18 suggested that the trial continues as planned. Translational research will be performed evaluating pharmacodynamic markers of efficacy such as immunogenicity response against Tedopi vaccine neoantigens, as well as parameters in liquid and tissue biopsies. End January 19, 87 patients (51 Tedopi, 36 Soc) have been enrolled. Clinical trial information: NCT02654587.

A four-parameter score has been identified as associated with overall survival (OS) in patients with advanced cancer with an estimated survival inferior to 6 months. Here, we tested its prognostic value for OS in patients who had received more than two lines of systemic therapy. We prospectively enrolled patients with advanced cancer who were going to receive a third or more therapeutic line outside classical clinical guidelines. The four parameters (Eastern Cooperative Oncology Group performance status, number of metastatic sites, serum LDH, and serum albumin) were collected at baseline, allowing to calculate the score, which sorted the patients in three groups, A, B, and C (low, intermediate, and high score, respectively). We then searched for correlations between this grouping and clinicopathological features particularly OS. From August 2013 to March 2014, 65 patients were enrolled and corresponded after determining their score to 26 patients in group A, 30 in B, and 9 in C. The median OS of the cohort was 4.4 months, and the 6-month OS was 42%. Overall survival was different between the three groups, with respective 6-month OS equal to 80% in group A, 17% in group B, and 0% in group C and respective median OS of 9, 2.3, and 1.6 months. Such prognostic value persisted in multivariate analysis. Similar OS differences were observed in patients with PS ≤2. This simple scoring should help oncologists identify which patients, after at least two lines of systemic therapy, might benefit from best supportive care alone.

// Michael Duruisseaux 1 , Benjamin Besse 2 , Jacques Cadranel 3 , Maurice Perol 4 , Bertrand Mennecier 5 , Laurence Bigay-Game 6 , Renaud Descourt 7 , Eric Dansin 8 , Clarisse Audigier-Valette 9 , Lionel Moreau 10 , Jose Hureaux 11 , Remi Veillon 12 , Josiane Otto 13 , Anne Madroszyk-Flandin 14 , Alexis Cortot 15 , Francois Guichard 16 , Pascaline Boudou-Rouquette 17 , Alexandra Langlais 18 , Pascale Missy 19 , Franck Morin 19 , Denis Moro-Sibilot 1 1 Centre Hospitalier Universitaire Grenoble Alpes, Thoracic Oncology Unit, Chest Department, Grenoble, France 2 Medical Oncology Department, Gustave Roussy, Villejuif, France 3 Assistance Publique Hopitaux de Paris, Tenon Hospital, Chest Department, Paris, France 4 Leon-Berard Cancer Center, Lyon, France 5 Centre Hospitalier Universitaire de Strasbourg, Chest Department, Strasbourg, France 6 Larrey Hospital, Chest Department, Toulouse, France 7 Centre Hospitalier Universitaire de Brest, Brest, France 8 Oscar Lambret Cancer Center, Medical Oncology Department, Lille, France 9 Centre Hospitalier Sainte Musse, Chest Department, Toulon, France 10 Centre Hospitalier General de Colmar, Louis Pasteur Hospital, Chest Department, Colmar, France 11 Centre Hospitalier Universitaire d’Angers, Chest Department, Angers, France 12 Centre Hospitalier Universitaire de Bordeaux, Respiratory Disease Department, Pessac, France 13 Antoine Lacassagne Cancer Center, Nice, France 14 Paoli Calmettes Institute, Marseille, France 15 Centre Hospitalier Universitaire de Lille, Thoracic Oncology Unit, Lille, France 16 Medical Oncology Department, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France 17 Assistance Publique Hopitaux de Paris, Cochin-Port Royal Hospital, Medical Oncology Department, Paris, France 18 French Cooperative Thoracic Intergroup, Department of Biostatistics, Paris, France 19 French Cooperative Thoracic Intergroup, Clinical Research Unit, Paris, France Correspondence to: Denis Moro-Sibilot, email: DMoro-Sibilot@chu-grenoble.fr Keywords: lung cancer, ALK, crizotinib, ceritinib, alectinib Received: September 28, 2016 Accepted: January 10, 2017 Published: February 26, 2017 ABSTRACT Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK -positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK -positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes. ALK -positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib. At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months. Unselected ALK -positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

9097Background: The incidence of lung cancer is increasing dramatically in women with recent findings as the preferential involvement of the EGFR pathway and the potential impact of hormonal factor...

To determine guidelines for the management of perineal small bowel fistula (PSF) after total or posterior pelvic exenteration.During 15 years, 315 curative pelvic exenterations were performed. PSF occurred in 15 patients (3.5%). We retrieved the precise modality of radiotherapy (fields and doses) and management of all patients (type of surgery, number of surgery and mortality). Delay of occurrence was divided in early (within 30 days or before hospital discharge) and delayed.All patients underwent surgery. Mortality rate was 13%. Fourteen patients (93%) had history of radiotherapy. No PSF was noted after anterior pelvic exenteration. Higher frequency of PSF was noted after total pelvic exenteration versus posterior pelvic exenteration (P = 0.04). Early PSF occurred in four patients (27%) with higher frequency of small bowel intraoperative injury. Late PSF occurred in 11 patients (73%) divided in small bowel injury in contact with pelvic staples (n = 4) and disease recurrence (n = 6, local recurrence or carcinomatosis). One patient had delayed PSF by ulceration of small bowel in contact with pelvic drain.PSF was a life-threatening complication of pelvic exenteration. Radiotherapy leads to weaken small bowel with difficulty of cicatrisation. During pelvic exenteration: (a) extreme careful dissection and interposition of great omentum could avoid small bowel injury, (b) control of pelvic vessels and closure of rectum remnant should not used staplers. Intraoperative management of PSF used successful simple repair in case of early PSF or segmentary resection indeed enlarged to right colon in case of delayed PSF. Postoperative courses had to use intravenous hyperalimentation and digestive tract discharge.

Introduction: Paclitaxel plus cisplatin is considered to be the standard first-line therapy for advanced ovarian cancer. Previous to this study, economic data on this combination resulted from randomised clinical trials (RCTs). Therefore, the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital. Method: A retrospective cost-effectiveness analysis, from the hospital-payer perspective, was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated between 1995 and 2000. Median overall survival (OS) was used as the primary endpoint. The quality-adjusted time was assessed by the quality-adjusted time without symptoms or toxicity (Q-TWiST) method. Direct medical costs were collected for each patient. Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of $US1 = 7 French francs. Several univariate sensitivity analyses were carried out varying unit costs, medical practices and administration of paclitaxel. Results: The incremental cost of the PC regimen was $US10 716 per patient. OS and quality-adjusted time were improved by 10.8 and 9.3 months with the PC regimen. The cost per life-year gained and per added QALY were $US11 907 and $US13 827, respectively. The robustness of the results was confirmed in sensitivity analyses. Conclusion: Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting. We reported higher incremental costs and lower clinical benefits than RCT-based findings, suggesting that RCT-based findings were clearly balanced by our pragmatic approach based on clinical practices. Observational studies can provide complementary and balanced data for decision making.

Farmer's lung disease (FLD) is common in the east of France. In the absence of the primary recognized FLD agent, Saccharopolyspora rectivirgula, its etiology remains unknown. A prospective case-control study was performed to find the etiology of FLD in this area. Eleven patients were matched with 11 healthy control farmers. Twenty-two urban subjects constituted the nonexposed control group. Microorganisms from cowshed air and fodder were identified and counted. The antigens of the microorganisms most frequently isolated at the 22 farms were used for serological tests. Farms of patients with FLD contained more Absidia corymbifera than those of healthy farmers (p < 0.05 in air, p < 0.01 in fodder). Electrosyneresis, performed with A. corymbifera somatic antigen, differentiated 9 of 11 patients with FLD from control subjects (p < 0.01). Other significant results were obtained with Eurotium amstelodami (p < 0.01) and Wallemia sebi (p < 0.05). In contrast, no significant results were obtained with the other seven antigens tested, including S. rectivirgula. Absidia corymbifera and, to a lesser degree, W. sebi or E. amstelodami are likely to be the main causes of FLD in this area. Modifications in working conditions over time could explain the emergence of these new contributing etiologies.

Background Lung carcinoid tumor and low grade glioma are two uncommon malignancies. Patients and methods We report the case of 24-year-old man who presented with respiratory disease. Imaging investigations showed a right lung tumor and histological analysis confirmed a typical carcinoid tumor. As part of initial staging, brain MRI revealed an asymptomatic right frontal lesion. First, a right pulmonary lobectomy was performed without adjuvant treatment. In second time, brain tumorectomy was performed. Histological examination confirmed the diagnosis of low grade glioma (LGG). The patient remained in complete remission 2.5 years after the initial diagnosis. Results This is the first case reporting the association between LGG and lung carcinoid tumor, while no association between LGG and a systemic tumor have been published to date. Association of lung carcinoid tumor with other malignant diseases has been reported but remained uncommon. Only minimal data support a potential molecular common origin. Conclusion This exceptional association may be fortuitous. However, their concomitant diagnoses suggest a potential association between both rare diseases. A genetic susceptibility remains possible.

International audience; Incidence of non-small cell lung cancer is increasing especially among elderly with about 40% arising in patients over 70 years old. Most of these elderly patients are under treated. Seventy-one patients with lung cancer over 70 years old were treated in Institut Paoli-Calmettes from January 2000 until December 2003 (male/female: 57/14). Median age was 75.5 years (70-92). OMS 0-1-2-3=4.2-60.6-25.4-4.2%, respectively. Comorbidities were represented by arterial hypertension, coronaropathy, cardiac failure, thrombo-embolism, respiratory failure, diabetes, vascular cerebral dysfunction, and renal failure. 29.6% of patients were without comorbidity, and 14.1% had at least three comorbidities. The averages of the Charlson comorbidity score and the Age-Charlson comorbidity score were 3.4 and 6.6, respectively. Histological characteristics: epidermoïd/adenocarcinoma/undifferentiated/small cells: 39.4%/26.8%/15.5%/9.9%. Most of them were advanced lung cancer: St IIIB=14 (19.7%) and St IV=37 (52.1%). Forty-six patients received chemotherapy (64.8%) with 40 patients (86.9%) with platin (carboplatin or cisplatin). The median number of treatment cycles was 4.1 (range 1-7). Two patients achieved complete response and 15 had partial response. The response rate was 39.6%. The 1-year survival rate was 48.5% and the estimated median survival time was 11 months (95%; 7-18 months) for all patients. The 1-year survival rate was 75% and 21.6% and the estimated median survival time was 25.9 months (95%; 12.6, ND) and 5.7 months (95%; 4.2-9.6) for stage IIIB and IV, respectively. Toxicities were judged acceptable with 19 hospitalizations after chemotherapy, for 16 patients who represent 34.8% of patients who received chemotherapy.Conclusions: Chemotherapy is feasible in elderly patients with lung cancer. Patients should be evaluated for chemotherapy based on their performance status and comorbidities especially with geriatric assessment rather than age alone. The chemotherapy with platinum seems to be tolerable and effective.

Background The phase II, open-label BRAIN study (ML21823; NCT00800202) is the first to assess the efficacy/safety of bevacizumab combined with chemotherapy in patients (pts) with ns-NSCLC and untreated CNS metastases. Investigation of CEC, CEP or CTC levels as potential markers of response to bevacizumab was undertaken. Methods In the B + CP arm, blood samples were taken before treatment on day 1 (d1) of cycle 1 (C1) (and 6 hrs after [C1 + 6h] treatment at one centre only), and on d1 of C2 and C3, i.e. 4 samples in total. Samples were taken for the B + E arm on d1 of C1, C2 and C3 (3 samples total). CEC and CTC levels were measured with CellSearch (Immunicon, Veridex). CEP were measured using four-colour flow cytometry after enrichment of progenitor cells using Miltenyi Biotec EPC enumeration and enrichment kit. Cut-offs were 15 cells/4mL for CEC, 2 cells/7.5mL for CTC and median for CEP. Relation between marker levels and 6-month progression-free rate (PFR) and best overall response (BOR) was examined. Results CEC and CTC were analysed in 69/91 (76%) pts, and CEP in 32/91 (35%) pts; baseline (BL) characteristics were similar to the overall population. CEC, CTC and CEP were detected at BL in 94%, 94% and 100% of these pts. In the B + CP group, CEC levels were increased at C1 + 6h, possibly reflecting the antivascular effect of chemotherapy. Furthermore, in the B + CP group, pts with higher BL CTC and no peak in CEC levels at C1 + 6h progressed at 6 months. Analysis of association of markers with BOR and PFR for the two regimens is ongoing. Conclusions Measuring CEC, CTC and CEP is feasible in NSCLC. Detailed analyses will be presented. The clinical value of these markers for predicting response to bevacizumab in advanced ns-NSCLC patients warrants further investigation. B + CP B + E Progression/death at 6 months Progression/death at 6 months CEC (cells/4mL) Median (range) No (n = 28) Yes (n = 19) No (n = 13) Yes (n = 8) C1 cells/4mL (n = 27) 24 (4–464) (n = 18) 32 (0–184) (n = 12) 28 (8–108) (n = 8) 44 (4–96) C1 + 6h cells/4mL change from BL (n = 9) 104 (12–632) 36 (-336–72) (n = 7) 28 (0–120) -16 (-172–100) – – C2 cells/4mL change from BL (n = 24) 24 (8–308) (n = 23) 0 (-376–268) (n = 15) 20 (0–216) (n = 14) -4 (-176–196) (n = 12) 34 (4–180) (n = 11) -4 (-72–160) (n = 8) 34 (0–356) (n = 8) -4 (-76–316) C3 cells/4mL change from BL (n = 26) 34 (0–228) (n = 25) 4 (-440–208) (n = 10) 30 (0–464) (n = 10) 10 (-172–444) (n = 11) 28 (0–76) (n = 10) 0 (-100–52) (n = 7) 76 (0–244) (n = 7) 28 (-20–192) CTC (cells/7.5mL) n (%) No (n = 28) Yes (n = 19) No (n = 13) Yes (n = 8) C1 ≥ 2 cells/7.5mL (n = 28) 24 (85.7%) 4 (14.3%) (n = 17) 8 (47.1%) 9 (52.9%) (n = 12) 10 (83.3%) 2 (16.7%) (n = 8) 7 (87.5%) 1 (12.5%) C2 ≥ 2 cells/7.5mL (n = 24) 21 (87.5%) 3 (12.5%) (n = 16) 10 (62.5%) 6 (37.5%) (n = 11) 9 (81.8%) 2 (18.2%) (n = 8) 5 (62.5%) 3 (37.5%) C3 ≥ 2 cells/7.5mL (n = 25) 22 (88.0%) 3 (12.0%) (n = 11) 7 (63.6%) 4 (36.4%) (n = 12) 12 (100%) 0 (0%) (n = 6) 4 (66.7%) 2 (33.3%) CEP (133+ CEP/1000 CD34+) Median (range) No (n = 12) Yes (n = 9) No (n = 7) Yes (n = 4) C1 (n = 12) 1.8 (0.0–4.3) (n = 9) 1.6 (0.0–5.9) (n = 7) 0.0 (0.0–2.1) (n = 4) 5.0 (0.2–7.1) C1 + 6h (n = 8) 1.5 (0.0–7.8) (n = 6) 0.0 (0.0–0.5) – – C2 (n = 12) 0.3 (0.0–5.8) (n = 7) 0.0 (0.0–3.3) (n = 6) 0.4 (0.0–3.2) (n = 4) 0.3 (0.0–1.1) C3 (n = 12) 1.2 (0.0–8.7) (n = 4) 0.0 (0.0–1.5) (n = 7) 0.7 (0.0–3.7) (n = 3) 1.8 (0.0–3.4) Disclosure H. Senellart: Financial Interest: Advisory Board. E. Dansin: Attended advisory boards for Roche, Lilly and Boehringer-Ingelheim. B. Besse: Received research grants from Roche. All other authors have declared no conflicts of interest.

Aim: In most cancers we do not have clear therapeutic guidelines after the second line of chemotherapy. A score, using 4 criteria, has been built from a multivariate analysis of a cohort of 177 advanced –stage cancers without specific treatment * and was clearly associated with the prognosis. Our aim was to test this score in patients receiving a 3rd or 4th + line in a palliative setting, in order to better define patients who will have a very poor prognosis and should benefit from best supportive care alone. Methods: Were included in this prospective series, patients with solid tumors (except breast cancer) who had received more than 2 chemotherapy lines in a palliative setting and who are planned to receive a third line. The day before the first cycle the 4 parameters were collected and the score calculated (PS 0-1: 0 Points; 2: 2 Pts; 3-4: 4 Pts – metastatic sites: 1: 0 Pts; > 2: 2 Pts - Albumin: 33 g/L - 3 Pts - LDH 600: 1 Pt; score = total + 3 Pts, ranging from 0 to 10) and associated with the outcome (overall survival – comparison by log-rank test ). Results: From August 2013 to March 2014, 64 patients were included. The primary was: sarcoma in 15 Patients, colo-rectal cancer: 14, lung cancer: 11, ovarian cancer : 11, pancreatic cancer: 5, gastric cancer: 4, other: 4.They have previously received: 2 lines in 32 cases, 3 in 17, 4 in 6 and more than 5 lines in 9 cases. Median overall survival (mOS) of the cohort was 4.4 mo, 3 and 6-mo OS were respectively 63 and 46 %. mOS was clearly related with the score. Patients with a good score (0 to 3; n = 27) had a mOS not reached and 3 and 6 mo OS of 100 and 67%; those with a score between 4–6 (n = 15) had a mOS of 3.4 mo, and 3 and 6 mo OS of 52 and 41% while those having a score from 7–10 (m = 22) had a mOS of 1.3 months and 3–6 months OS of 25–0%. Overall survival was significantly (log-rank) different (p Conclusions: Conclusions: this score, very easy to determine, will help medical oncologist to decide which patients should not receive an additional line of chemotherapy due to predicted poor overall survival under treatment. *Barbot AC, et al. J Clin Oncol 2008; 15: 2538-43 Disclosure: All authors have declared no conflicts of interest.

Aim: TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16 + CD56 + CD69+) might be a predictive biomarker for TG4010 efficacy in NSCLC (Lancet Oncol 2011;12:1125-33). TIME is a double-blind phase 2b/3 study (NCT01383148) comparing the combination of first line therapy with TG4010 or placebo. The Phase 2b part aims at prospectively validating the baseline TrPAL level as a predictive biomarker. Methods: Primary endpoint of the Phase 2b part of the study was to compare progression-free survival (PFS, according to RECIST 1.1) between TG4010 and placebo arms using a Bayesian design, in stage IV NSCLC patients with a MUC1+ tumor. Secondary objectives were response rate, safety, survival and subgroup analyses. A dynamic minimization procedure was applied at randomization for histology, prescription of bevacizumab, type of chemotherapy, performance status and center. Results: 217 patients have been enrolled out of which 170 patients with a normal TrPAL level (pre-determined threshold) and an analysis of PFS was conducted in this cohort after 137 events of progression were recorded. The hazard ratio (HR) for PFS is 0.76 (95%CI: 0.54-1.06). This corresponds to a 97.5% Bayesian probability that the true HR is Conclusions: These data support the predictive value of the TrPAL biomarker. They also confirm TG4010 efficacy and safety profile in stage IV NSCLC patients and warrant the continuation of the TIME study with its Phase 3 part. Disclosure: E. Quoix: Transgene: joint steering committee member and consultant; C. Chouaid: Consultant for Lilly, GSK, Amgen Advisory board member: Lilly, Roche, AZ, Amgen, Boheringer Ingelheim; Z. Papai: Advisory board member for Transgene; V. Westeel: Advisory board member for Roche, Lilly. Honoraria from Astra Zeneca, Boehringer, Teva; G. Lacoste: Transgene employee. Stockoption ownership; A. Tavernaro: Transgene employee. Stockoption ownership; B. Bastien: Transgene employee. Stockoption ownership; T. Palanche: Transgene employee with Transgene stock options; J. Limacher: Transgene employee. Stock option owner. All other authors have declared no conflicts of interest.

Aim: Lung cancer in patients under 40 years is infrequent and few data are available about the presentation and outcomes of lung cancer in this population. This study aimed to describe the clinical characteristics, the treatments and the outcome of lung cancer occurring in the population of young adults in France. Methods: A prospective observational clinical study was conducted in 37 centers in France. All patients under 40 years diagnosed with lung cancer between November 2010 and December 2013 were enrolled. Results: One hundred and fifty nine patients with lung cancer were included. Intermediate results are currently available for 117 patients. Median age at diagnosis was 38 (20-40). The proportion of men was 58%. Median time between symptoms and diagnosis was 2 months. The distribution of stages I- II, IIIA and IIIB-IV was 9%, 9% and 82% respectively; 66% were diagnosed with metastasis at presentation and the first metastasis site was brain in 47% of patients. Adenocarcinoma was the most common histologic subtype (78%). EGFR screening was performed for 83 patients and 10% of the patients had an activating mutation. Analysis of other driver biomarkers is ongoing. Eighty-four patients (86%) were current or former tobacco smoker with a median of 20 packs -year. Sixty-nine patients (59%) have been exposed to passive smoking essentially in childhood. About half of them (46%) were current or former cannabis smoker (among which 50% regularly). Socioeconomic status was lower comparing to general population, 24% of the patients had no diploma. The first line treatments were 88% chemotherapy, 43% radiotherapy, 21% surgery and 5% best supportive care. Median overall survival was 14.7 months. Conclusions: This study is the first national prospective study dedicated to patients under 40 years diagnosed with lung cancer. Compared to the general population of lung cancer, our preliminary results show a high proportion of women, adenocarcinoma histology, advanced disease at diagnosis and tobacco and cannabis use. Final analysis will be presented at the congress. Disclosure: All authors have declared no conflicts of interest.

7505 Background: Surgical resection followed by adjuvant platinum-based CT is the standard of care in stages II and III of NSCLC. ERCC1 is considered as a molecular determinant of benefit to platin-based CT and is an independent good prognostic marker in resected NSCLC. EGFR mutations predict for erlotinib efficacy. We included ERCC1 IHC status and EGFR mutational status in a prospective randomized multicentric phase II/III customized adjuvant CT trial. Methods: Completely resected patients (pts) with non-squamous tumors, mediastinal lymph node dissection and pathological stage IIA, IIB or IIIA (N2 excluded) (6th TNM edition) were randomized either to a control arm (A) or a customized arm (B). Surgical blocks were centralized for biomarkers analyses. The control arm encompassed 4 cycles of standard dose cisplatin-pemetrexed (CP). In the experimental arm, EGFR mutated pts received erlotinib 150 mg for one year. ERCC1 negative pts received four cycles of CP. ERCC1 positive pts were closely monitored. The Fleming’s single stage phase II primary endpoint was feasibility (ie % of patients able to start therapy within 2 months of surgery and for which the biomarker’s status was readily available) (H0 64%, H180%, α 5% and β 95%). Results: 150 pts were randomized between May 2009 and July 2012, 74 in arm A and 76 in arm B. Most pts were male (61%), ≤ 60 years (51%), and smokers (91%). Pathological stage was IIA in 69 pt, IIB in 48 pt and IIIA in 32 pt. ERCC1 was positive in 38 pts (19 in each arm), EGFR mutation was identified in 10 pts (3 in arm A, 7 in arm B). In arm A, all pts received CP. In arm B, 7 pts received erlotinib, 53 pts received CP and 16 were followed-up. The median exposure time to erlotinib was 276 days (10-365). Out of 127 pts allocated to CP, 82% received the expected 4 cycles with a very good tolerability profile (no febrile neutropenia). The success rate was 80% (120 out of 150 pts). Conclusions: This adjuvant trial met its primary end point for its phase II component, demonstrating the feasibility of a national biology-driven trial in the adjuvant setting. Nevertheless the phase III was canceled due to the unexpected unreliability of the ERCC1 IHC read-out. Clinical trial information: NCT00775385.

Background This non-comparative randomised trial (EUDRACT 2008-005013-21) aimed to assess the feasibility of combining cetuximab (C) with cisplatin (P) + vinorelbine (V) + radiotherapy (R) or with P + etoposide (E) + R in selected stage IIIA/B NSCLC PTS. ARM A N (%) ARM B N (%) PTS with at least one ≥ grade 3 NHTNV 12 (36) 15 (48) More frequent events - Esophagitis 2 (6) 8 (26) - Fatigue 2 (6) 2 (7) - Thrombosis/embolism 2 (6) 2 (7) - Acneiform rash 3 (9) - - Febrile neutropenia - 2 (7) - Hemoptysis - 1 (3)* Methods Eligibility criteria included age Results Ninety PTS were enrolled and 64 PTS were randomised: 33 in arm A, 31 in arm B. The major reason for non-randomisation was dosimetric failure at D21. 27 PTS experienced ≥ grade 3 NHTNV (Table). The rate of serious adverse events was 30% in arm A and 55% in arm B. Objective response rate and PFS rate at 1 year were 79% and 57% (95%CI: 36-73), respectively, in arm A and 69% and 43% (95%CI: 20-64), respectively, in arm B. Conclusion The concurrent association of C with P-based chemoradiotherapy seems to be safe and active in both arms, with a slight advantage for arm A, and deserves further evaluation in a phase III study. *, grade 5. Disclosure All authors have declared no conflicts of interest.

Background Incidence of MSCC is increasing, paralleling increasing life expectancy of patients (pts). We analyzed pts referred for surgery for MSCC to evaluate scoring system relevance, prognosis factors, efficiency and safety. Methods From 2004 to 2010 148 pts (77 men) with oncologic (84%) and hematological (16 %) diseases had surgery for MSCC. Patients and tumoral characteristics were recorded. Prognostic value of Tomita, Tokuhashi scores, ASA score, Frankel score (FS) and pain was investigated. Results Median age was 60 y (22–87). Lung (17%) and breast cancer (18%), were mainly represented. Multiple extra-bone metastases were observed in 39% of pts. Pain was present in 96% of pts and 66% were hyperalgic (pain score > 6). FS was decreased for 49% of pts and median Karnofsky Performance Scale (KPS) was 70%. Majority had laminectomy with spinal fixation: 73 %. Radiotherapy was done for 68%. Median overall survival (OS) was 8.9 months (IC95: 4.4–13). Tokuhashi but not Tomita score was relevant. Survival predictive accuracy of TS was only 51%. By univariate analyses, moderate pain (p = 0.001), primary breast (p = 0.02) or hematological (p 70 (p Conclusion Surgery for MSCC is associated with limited morbidity, improvement of patients' autonomy and remission of pain. In our study, usual scores seem not relevant, whereas ASA score, KPS and extra-bone metastases are significant survival prognostic factors. Disclosure All authors have declared no conflicts of interest.