Performans Status Research Articles

1087P - Head and neck cancer (HNC) and synchronic lung cancer: Impact of the lung cancer on the management and prognosis of these patients. Data from the SYNCHRON GFPC 15-04 Study

Background: Management of synchronous head and neck and lung cancer is almost difficult. The aim of this observational study was to describe the impact of the lung cancer on the management and prognosis of HNC. Methods: Inclusion criteria were: consecutive patients diagnosed between January 2011 and December 2015 in 19 French centers with HNC and synchronous lung cancer (all stages). We describe: clinical characteristics, management and outcomes. Patient characteristics and treatment information was analyzed descriptively. Kaplan-Meier estimation was used to assess median overall survival. Results: The study included 132 patients: men: 83%; 63,7 years old, current smokers: 59,8%; performans status: 0 and 1 for 22% and 66% of the patients respectively; high rate of comorbidities: cardiovascular: 63%, COPD: 33%. Main histology for HNC was squamous: 98%, (in oral cavity: 24%, oropharyngeal: 26%, hypo-pharyngeal: 22% and laryngeal: 28%) T classification was T1, T2, T3 and T4 in 16%, 24%, 28% and 18% of cases respectively, and N classification was N0, N1, N2, N3, for 36%, 18%, 20% and 8% of cases respectively. The main treatment was surgery, 37,1%, and chemo-radiotherapy, 35,6%. The diagnosis of lung cancer impacts the HNC management in 38% of the cases. Median delay between HNC and first day treatment was 54 days. HNC progressive free survival rate was 68% at 2 years. Lung cancers were mostly localized (stages I: 46%, stages II: 10%), squamous: 39%, or adeno-carcinomas: 39%. Main treatments were surgery: 29%, mainly lobectomy, radiotherapy: 13%, radio-chemotherapy: 14% and chemotherapy alone: 35%. Seven patients didn’t receive active treatment. Median delay of treatment was 82,3 days. Lung cancer progressive free survival rate was 35% at 2 years. OS was 40% at 2 years, better for stage I - II lung cancers (55%). Conclusions: Synchronous lung cancer at HNC diagnosis significantly impacts the management and outcomes of HNC. Specific recommendations and multidisciplinary approach should be elaborate to improve the management of these patients. Legal entity responsible for the study: Groupe Français de Pneumo-cancérologie Funding: Boringer Pierre Fabre Disclosure: All authors have declared no conflicts of interest.

Quelle est la meilleure séquence thérapeutique pour les CBNPC non-opérables ?

Despite the progress in therapeutic strategies, overall survival of stage III non-small cell lung cancers (NSCLC) is poor. Currently, the standard treatment of unresectable locally advanced NSCLC is concurrent chemoradiotherapy. This schedule is probably beneficial for patients in good performans status, without important co-morbidities and often younger than 70 years. Platin-based chemotherapy should be administered at cytotoxic doses. Many questions remain debated:• The choice of chemotherapy regimen,• The benefit of induction and consolidation chemotherapy is not proven,• The modalities of radiation in terms of doses, fractionation,• The integration of targeted therapies in this scheme, particularly EGFR inhibitors• The integration of immunotherapy.The improved results in recent clinical trials appears to be partly linked to better patient selection through optimization of diagnostic imaging. The new radiation modalities should improve results especially in terms of local control. Similarly, the arrival of new therapeutic approaches such as immunotherapy may change the management of these patients.

Management of patients with head and neck cancer (HNC) and synchronic stage I or II lung cancer. SYNCHRON GFPC 15-01 study.

e20048 Background: There is few published data’s of the management of patients with a HNC and a synchronic lung cancer. The aim of this observational study was to describe in a multicentric setting the management of these patients. Methods: The study included, consecutively all patients diagnosed between January 2011 and December 2015 in 19 French centers with a HNC and a synchronic lung cancer. Patients were described per the clinical characteristics, management and outcomes. Patient characteristics and treatment information was analyzed descriptively. Kaplan-Meier estimation was used to assess median overall survival. Results: The study included 62 patients: men : 84%; 62 ± 1.3 years old, current smokers: 68%, asbestos exposure: 11%; performans status: 0 and 1 for 22.5% and 66% of the patients respectively; hight rate of comorbidities, cardiovascular: 68%, COPD: 32%. Main histology for HNC was squamous: 98%, in oral cavity: 32%, oropharyngeal: 21%, hypo-pharyngeal: 22.5% and laryngeal: 24%. T classification was T1, T2, T3 and T4 in 18%, 29%, 29% and 16% of cases respectively, and N classification was N0, N1, N2, N3, for 40%, 24%, 21% and 6% of cases respectively. The main treatment was surgery, 47%, and chemo-radiotherapy, 52%. The diagnosis of lung cancer impacts the HNC management in 21% of the cases. Median delay between HNC and first day treatment was 54 ± 6 days. HNC progressive free survival rate was 68% at 2 years. Lung cancers were localized (stages I: 81%, stages II: 19%), squamous: 32%, adeno-carcinomas: 47%, larges cells or sarcomatosis: 7%. Main treatments were surgery: 56%, mainly lobectomy, radiotherapy: 15%, radio-chemotherapy: 10% and chemotherapy alone: 26%. Six patients didn’t receive active treatment. Median delay of treatment was 150 ± 16 days. Lung cancer progressive free survival rate was 28% at 2 years. OS was 55% at 2 years, better for stage I than stage II lung cancers. Conclusions: Synchronic lung cancer at HCN diagnosis impact management and outcomes of HNC with a delay in the management of lung cancer. Specific recommendations should be elaborate to improve the management of these patients.

Characteristics of very long responder to maintenance cetuximab after a platinum-cetuximab based chemotherapy for recurrent and/or metastatic head and neck squamous cell carcinomas (RM HNSCC).

e17524 Background: Standard treatment for first line RM HNSCC is the association of platinum-5FU and cetuximab. For non-progressive patients (pts), cetuximab is given weekly as maintenance until progression or unacceptable toxicity. In the EXTREME protocol (Vermorken et al, NEJM 2008), this strategy showed an OS of 10.1 months with a mean duration of maintenance of 3 months. This study aimed at describing pts who have benefited from a cetuximab maintenance for a longer period (i.e. > 6 months). Methods: We did a retrospective study in 7 centers in France. Inclusion criteria were: pts > 18 years with a RM HNSCC treated between November 2009 and January 2017, with platinum based chemotherapy and cetuximab followed by weekly cetuximab maintenance of more than 6 months. Results: 53 pts (45 male), with a median age of 57 [38-76] were recorded. Median follow-up was 63.7 months [14.8-237.6]. 72% [37/53] had an oral cavity or oropharynx tumor location with a well or moderately differentiated carcinoma (74%). 45/53 (85%) were smokers and 4/21 (19%) p16 positive. 46/53 (87%) had a Performans Status of 0-1. Mean BMI and albumin level were respectively 22.5 [SD: 4.19] and 40g/l [SD: 4.9]. EXTREME regimen was used for 44 pts, 2 pts had platinum and cetuximab and 7 received platinum, docetaxel and cetuximab. Mean number of chemotherapy cycles was 5 [3-7]. After chemotherapy, the number of pts with complete response (CR), partial response (PR) or stabilization was respectively 5 (9%), 23 (43%) and 25 (47%). 2 pts in PR finally achieved CR during maintenance. One of them stopped cetuximab and was still in CR 5 months later. Mean duration time of maintenance by cetuximab was 11 months [6-24]. Toxicities were mainly cutaneous: 47/53 pts had toxicities, of which 6 had grade 3. Presence of cutaneous toxicities seemed to be correlated with a longer response (p = 0.01). PFS and OS were respectively 15.5 and 27.4 months. Conclusions: Our study allowed us to identify a cohort of long responder pts to maintenance cetuximab including 2 pts who obtained a complete response. More analysis should be done to identify biomarkers able to predict long responder.

Antitumor activity of abiraterone, enzalutamide, and docetaxel following treatment with diethystilbestrol in castration-resistant prostate cancer.

e581 Background: Docetaxel and Next-Generation Anti-Androgens (NGAA) including abiraterone and enzalutamide represent the standard of treatment for patients with castration-resistant prostate cancer (CRPC). Treatment sequencing of these agents is a challenge. Recent studies identified cross-resistances between hormonal therapies and taxanes, as well as between different NGAA. In aiming to elucidate whether synthetic oestrogen diethylstilbestrol (DES) therapy impacts the efficacy of later-line treatments or not, we evaluated the antitumor activity of NGAA and docetaxel following DES therapy in CRPC patients. Methods: All patients with CRPC treated at Pitié-Salpêtrière hospital in first-line setting with DES from September 1995 to July 2016 were retrospectively identified. We evaluated further activities of abiraterone, enzalutamide and docetaxel in those patients after DES therapy, using Prostate Cancer Working Group 3 criteria. Clinicopathologic characteristics, including age, performans status, metastatic sites at diagnosis and treatments initiation, and data survival were also assessed. Results: Twenty-three patients with CRPC were initially treated with DES with a median time to prostate-specific antigen (PSA) progression of 9.7 months (range, 4.7-20.3). Thirteen patients(56.5%) received abiraterone or enzalutamide before docetaxel and 21 patients (91.3%) after. Median age at first NGAA initiation was 79 years) range, 55-91). Only one patient (7.7%) achieved a PSA decline before docetaxel and two out of 18 evaluable patients (11.1%) after docetaxel. Median time to PSA progression and overall survival with a NGAA treatment were respectively 2.8 (range, 2.0-4.1) and 16.5 months(range, 4.3-31.0). Fifty percent of patients showed a PSA response with docetaxel. No clinical factors were found to be significantly associated with PSA response to NGAA treatment, nor to docetaxel. Conclusions: The activity of NGAA appears markedly limited after a DES therapy, regardless of the PSA response to docetaxel. These data suggest the likelihood of a cross-resistance mechanism between DES and NGAA, without no impact on taxanes pathways.

Abstract OT1-04-07: VICTORIANE: A randomized phase 3 study assessing the addition of oral vinorelbine to aromatase inhibitors for the treatment of patients with metastatic breast cancer

Abstract Background : The addition of anti-proliferative agents such new inhibitors of CDK4/6 to hormonotherapy have significantly improved the efficacy in patients with metastatic breast cancer (MBC). Oral vinorelbine provided the opportunity to give new schedules of chemotherapy with favourable tolerability and prolonged exposure. The present trial was designed to evaluate the clinical effects of the addition of oral vinorelbine to aromatase inhibitors in first line treatment for MBC. Methods : In this phase III, randomized, prospective, open trial named VICTORIANE (NCT02730091), postmenopausal women with HR+/HER2– with MBC are randomized (1:1) between letrozole or anastrozole once a day (Arm A) versus oral vinorelbine 50 mg three times a every week with letrozole or anastrozole (Arm B). Continuous daily schedule (days 1-28 of each 28 days cycle) is planned until disease progression or discontinuation for other reasons. A minimisation algorithm was used stratifying treatment allocation according to the existence of visceral metastases, prior adjuvant hormonal treatment and centers. The study is conducted in compliance with the principles of good clinical practice and the declaration of Helsinki. Key inclusion criteria include, histologicaly proven HER2-negative and Estrogen Receptor-positive breast cancer, metastatic setting, no prior systemic anti-cancer therapy for MBC, recurrence after prior hormonal therapy in the adjuvant setting is allowed if disease free interval is greater than 24 months from the completion of treatment, normal liver, bone marrow and renal functions, Performans status greater than 2. Non inclusion criteria include symptomatic visceral disease, or disease burden precluding endocrine therapy, and prior therapy with vinorelbine. The primary endpoints is progression-free survival (PFS; local assessment, RECIST v1.1) and secondaries endpoints are overall survival, health-related quality of life, overall response rate and safety. Analysis of the primary endpoint will be performed with a stratified log-rank test (95% confidence interval). A 30 percent reduction in the risk of events (Hazard Ratio (HR) = 0.70) was assumed under H1 in the arm B. This reduction was estimated based on an absolute gain of 3.857 months in terms of median PFS, from 9 months (arm A) to 12.857 months (arm B). Global recruitment of the planned 340 pts is ongoing and should be completed in march 2018. Final results will be expected in 2019. Citation Format: Villanueva CB, Barthelemy P, Ferrero JM, Jacquin JP, Bonnetain F, Mansi L, Pivot X. VICTORIANE: A randomized phase 3 study assessing the addition of oral vinorelbine to aromatase inhibitors for the treatment of patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-07.

P3.02c-089 ImmunoCHIC: A Prospective Nivolumab Monotherapy Cohort in Advanced Non-Small Cell Lung Cancer Patients in Routine Clinical Practice: Topic: IT Biomarkers

In France, in May 2015, Nivolumab early access program was established for patients with advanced NSCLC progressing during or after platinum-based chemotherapy. There is little evidence of Nivolumab use out of clinical trials. We report here one year of Nivolumab use in a French University hospital. Observational prospective review of patients with advanced NSCLC treated with Nivolumab monotherapy (3 mg/kg/2weeks) in our center, in routine clinical practice. Patients in clinical trial were excluded. Analyze was done on clinico-pathological features, tolerance and outcomes. 63 patients were included (men: 76.1%, age: 65 (range: 40–78), squamous: 33.3%; smoker: 93.7%%, EGFR/ALK negatives: 98.4%, unknown PDL1: 70%; at least one significant comorbidity: 54%; performans status 0/1/2: 34%/49%/17%; cerebral metastasis: 38%; nivolumab as second, third and more than third lines: 38%/38%/24%. Median number of nivolumab cycles: 6 (1-24), more than 12 cycles: 20.6% Disease control rate : 59% (3 complete responses) ; Clinically significant adverse event: 13 (20%) patients (asthenia: 4 patients, grade 2 to 4 colitis: 3 patients, pneumoniae: 3 patients, nephritis: 1 patient). After Nivolumab, 50% of the patients received an another systemic therapy. Two patients were able to go back to work. In real life setting, nivolumab had the efficacy level reported by pivotal clinical trial but with a higher rate of clinically significant adverse events, particularly colitis.

Incidence et facteurs de risque de l’encéphalopathie à l’ifosfamide chez les patients suivis pour un sarcome

Ifosfamide remains one of the major cytotoxic drugs for sarcoma management. Ifosfamid-related encephalopathy (IRE) is a rare but severe adverse event, without clearly identified risk factors. We have carried out a single-center, retrospective study to assess the occurrence and the risk factors for IRE after the two first cycles of chemotherapy. We have collected the data-describing patients, biological data, tumors characteristics (histology, leptomeningeal metastasis) and ifosfamide administration modalities. From September 2008 to November 2013, we have identified 8 IRE out of 187 patients (4.2% [CI95%: 1.8-8.2]). The median age was 27 (0-78). Histologies were adult soft tissue sarcomas (78 patients), osteosarcoma (48), ewing sarcoma (41) and rhabdomyosarcoma (26). Most of factors were not associated with IRE. Only 8 patients have received aprepitant, none of them experienced IRE. Under univariate analysis, the risk factors for IRE were: PS≥2 (OR=9.52 [CI95%: 2.38-38.80]), albumin≤36g/L (OR=9.79 [CI95%: 1.19-80.26]), leptomeningeal metastasis (OR=13.20 [CI95%: 2.76-63.19]), 4 or 5 successive days of ifosfamide administration (OR=6.00 [CI95%: 1.40-25.60]). Under multivariate analysis, the risk factors for IE were: PS≥2 (OR=16.00 [IC95%: 2.80-67.00]), leptomeningial metastasis (OR=23.56 [IC95%: 2.01-456.80]) and 4 or 5 days of ifosfamide administration (OR=57.45 [IC95%: 1.66-35.00]). Ifosfamide administration must be given with caution in patients with poor performans status. A 4 to 5 days fractioned ifosfamide and leptomeningeal metastasis seems associated with increased risk for IRE, whatever the total administered dose.

A Phase I/II Study of Vaccination By Autologous Leukemic Apoptotic Corpse Pulsed Dendritic Cells for Elderly Acute Myeloid Leukemia Patients in First or Second Complete Remission (LAM DC trial)

Introduction: A number of approaches have been explored to prevent relapse in AML setting, including immune-strategies such as dendritic cells (DC) vaccination. There is no report so far of the use of autologous apoptotic leukemic cells as a source of tumor antigen for DC vaccine.Methods: The main objective of this prospective monocentric Phase I/II study was to explore the feasibility to produce autologous leukemic apoptotic corpse-pulsed DC for elderly AML patients in first or second complete remission (CR) and to report the toxicity of such a vaccine. Inclusion criteria were AML (except promyelocytic) patients older than 59 years with a good performans status (ECOG <=2), not eligible for allogeneic transplantation or another trial, with >=50% of leukemic blasts in bone marrow (BM) or peripheral blood, and with no contra-indications to apheresis. Vaccines were produced by Nantes UTCG according to good manufacturing practices for cell and gene based therapies in order to comply to the French AFSSAPS (currently ANSM) agency guidelines. Patients had to be pre-included (refractory or not) at diagnosis or at time of first relapse in order to collect sufficient leukemic cells (>2.4 108) prior to chemotherapy after 1 or 2 days of collection. After blasts collection, the choice of chemotherapy regimen was at the discretion of the investigator. Few courses of chemotherapy were allowed before vaccine production but not after. Patients were definitively included only in case of CR to allow collecting autologous non-leukemic peripheral monocytes by apheresis to generate the DC vaccine. Patients were programmed to receive up to 5 doses of vaccine (days +1 +7 +14 +21 and +35 +2) which consisted of 10 millions pulsed DC, including 9 millions administered subcutaneously (1 mL) and 1 million administered intradermally (0.1mL). Minimal residual disease (MRD) was studied after vaccines using flow cytometry.Results: Between November 2009 and March 2015, 23 patients were pre-included but 2 patients were excluded for analyses because blast collection was finally not performed. Thus, overall, 21 elderly AML patients (male n=14; median age: 74 years (range: 65-84), secondary AML n=8) were considered either at time of diagnosis or at time of first relapse. The median % of BM blasts was 63% (range: 20-92), including 3 and 4 cases with less than 40% and between 40-49%, respectively (protocol deviation). Although it was not the case for one patient with >50% of BM blasts, all patients between 40-49% of BM blasts reached the threshold of 2.4x108blasts required for the study. Two patients out of 3 with less than 40% BM blasts had insufficient blast collection to pursue the protocol. After blast collection, the majority of patients (n=19) received non-intensive chemotherapy. 5/21 (24%) cases achieved CR, a rate that was expected for this very old population. All of CR patients could proceed to apheresis after 2 (n=4) or 4 (n=1) courses of non-intensive consolidation. Production of the 5 vaccines was possible for all of them and first infusion was made at a median of 25 days (range: 20-28) from the apheresis. However, a median of 27 vaccines (range: 8-85) could have been theoretically produced in CR patients, suggesting the possibility to realize a longer maintenance therapy to prevent relapse in the future.All patients received as expected the 5 vaccines and no adverse events were documented. Durations of response from CR were: +8.5, +8, +4.5, +4, +12 months and from first vaccine: +5.5, +4.5, +1.8, +1.8, and +9 months. Two patients had relapsed before day+55. At this time, the 3 other patients were documented with negative MRD. In July 2016, 2 patients are still alive, 1 at +30 months from CR in relapse and 1 at +13 months in CR. The 3 other cases died of relapse at +15.5, +8 and +5.5 months from CR. The median OS from pre-inclusion was significantly higher for vaccinated CR patients (13 months (9-41) vs 4.75 months (1-24), p=0.009).Conclusion: Our strategy seems promising for elderly AML patients achieving CR in terms of relapse prevention. Vaccine production is reproducible and compliant for clinical use. Larger Phase 2 studies are required to confirm our results in younger and older AML population. The trial is registered at Clinicaltrials.gov NCT01146262. This study was supported by a grant from the French National Cancer Institute. DisclosuresMoreau:Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria; Takeda: Honoraria; Amgen: Honoraria.

1090P - Identification of patients at risk for severe toxicity under PD1 inhibitors: role of sarcopenic overweight

PD-1 checkpoint inhibitors are associated with a specific spectrum of immune-related adverse events (irAEs). Body composition has been proven to influence the pharmacokinetics of many anti-neoplastic drugs. We evaluated the effect of decreased muscle mass (sarcopenia) on PD-1 inhibitors toxicity. Pre-therapeutic biological and clinical assessments were prospectively performed for patients (pts) treated with anti-PD1. Muscle mass was estimated using Creatinine/Cystatine C (Cr/CysC) clearance ratio (Kim SW, 2016). Univariate and multivariate analysis tested the association between anti-PD1 induced severe toxicity and age, sex, Performans Status (PS), (Cr/CysC) clearance ratio, body mass index (BMI), lymphocytes, C-Reactive Protein (CRP) and albuminemia. The severity of AEs was graded according to the NCI CTC for AE V4. From July 2015 to April 2016, 74 pts, median age 65 years (41-84), 58.1% men, received at least one infusion of nivolumab (85%) or pembrolizumab (15%), for lung cancer (n = 44), melanoma (n = 13), renal carcinoma (n = 9) and others (n = 8). A total of 418 cycles (median per pt: 4, range 1-20) were analyzed. Median Cr/CysC clearance ratio was 1.17. Twenty pts (27%) had both Cr/CysC clearance ratio >1.17, reflecting low lean body mass and a BMI > 25 kg.m-2. Fifteen pts (20.2%) developed grade 3-5 AEs, some rare, such as insipid diabetes with hypophysitis (n = 1) after 1st cycle (C1), pulmonary arterial hypertension (n = 3, C1, C1, C5), polymyositis (n = 2, C2, C2) and thrombocytopenia (n = 1, C6). In univariate analysis, gr 3-5 AE was associated with Cr/CysC clearance ratio >1.17 (p = 0.006), high CRP (p = 0.036) and the combination of Cr/Cyst clearance ratio >1.17 with BMI > 25 kg/m2 (p= 0.024). In multivariate analysis, Cr/CysC clearance ratio >1.17 (p = 0.03) and the combination of Cr/CysC clearance ratio >1.17 with BMI >25 kg/m2 (p = 0.014) remained significant. The Creatinine/Cystatine C clearance ratio associated with BMI helps to identify sarcopenic overweight pts who are at high risk of severe PD-1 inhibitors induced toxicity. To date, it is unknown if the development of irAEs is an inherent component of checkpoint blockade with anti–PD-1 or if modifying the dosage can decrease the rates of these events.

R-DHA-Oxaliplatin Versus R-DHA-Cisplatin Regimen in B-Cell Nhl's Treatment: A Eight Years Retrospective Study

Background: R-DHAP regimen (rituximab, cisplatin, dexamethasone, high dose cytarabine) based on the 1988 Velasquez's study is a standard scheme used to treat relapsed Non-Hodgkin lymphomas (NHL). Cisplatin is frequently substituted with oxaliplatin to avoid nephrotoxicity, resulting in R-DHAX that is currently prescribed in first or second line treatment for aggressive NHL. However data are scarce. We compared the nephrotoxicity of cisplatine to oxaliplatine in R-DHA-platinum in this setting.Methods: All consecutive patients with NHL treated by R-DHAP or R-DHAX in Angers hospital between the 1st January 2007 and the 31th December 2014 were included. Either cisplatin 100 mg/m2 during 24 hours (R-DHAP) or oxaliplatin 130 mg/m2 during 2 hours (R-DHAX) were associated at d1 with cytarabine (2000 mg/m2 during 3 hours, two doses, d 2), dexamethasone (40 mg, d 1-4) and rituximab (375mg/m2, d 1) (Details on table 1). Cisplatin dosage were reduced from 25% to 50% according to individual renal tolerance. Up to 6 courses were delivered. Serum creatinine was recorded before each course of chemotherapy and was checked between d3 and d15 after administration, allowing to trace individual profiles of trajectories for their levels. These trajectories were clusterized in order to detect the existence of homogeneous patterns of evolution. This is a classical, semiparametric group-based statistical approach (Ref 1). Concomitant nephrotoxic drugs and events (sepsis…) were recorded to identify potential bias.Results: 21 patients received R-DHAP and 32 received R-DHAX. 6 patients switched from R-DHAP to R-DHAX due to nephrotoxicity. 2 different homogeneous clusters appeared. Cluster A included a majority of R-DHAX: 31 R-DHAX (88.6%), 3 R-DHAP (8.6%), 1 R-DHAP who changed to R-DHAX (2.9%). Cluster B contained a majority of R-DHAP: 11 R-DHAP (64.7%), 1 R-DHAX (5.9%), 5 R-DHAP to R-DHAX (29.4%) (p = 7.5.10-9). Cluster A graphic profile appeared less toxic than cluster B according to average serum creatinine level (mean cluster A: 70.2 µmol/L; mean cluster B: 99.5 µmol/L (p = 2.2.10-16)). Patients treated with R-DHAP experienced more severe renal failure than patients treated with R-DHAX (Chi-square test: p = 2.9.10-8, table 2). Nephrotoxic concomitant treatments have no significant discriminant effect. No differences were observed between either R-DHAP versus R-DHAX or cluster A versus B patients, as regards to age, sex, malnutrition status, histology, stage of the lymphoma, performans status, comorbidities including renal comorbidities and the history of nephrotoxic therapy. No significant difference was shown in OS and EFS (respectively, p = 0.463 and p = 0.290).Conclusions: Although R-DHAX is now widely used in NHL treatment, our study is one of the first to evaluate efficacy and renal tolerance of this treatment. R-DHAX nephrotoxicity is not significant whereas most patients receiving R-DHAP had significant acute renal impairment. We found no difference as regards to survival. A prospective study should compare these schedules in NHL to adapt future practices and improve morbidity.Table 1Patients characteristicsCaractéristicsDHAPDHAXTotalSexM14 (66.7%)23 (71.9%)37 (69.8%)F7 (33.3%)9 (28.1%)16 (30.2%)Age (years)Median (min-max)61 (34-80)61 (39-77)61 (34-80)BMI< 1800018 to 259 (42.9%)17 (53.1%)26 (49.1%)> 2512 (57.1%)15 (46.9%)27 (50.9%)Performans Status (N=49)PS > = 23 (17.6%)2 (6.3%)5 (10.2%)PS < 214 (82.4%)30 (93.8%)44 (89.8%)ComorbiditiesRenal1 (4.8%)3 (9.4%)4 (7.5%)Cardiovascular8 (38.1%)13 (40.6%)21 (39.6%)Other12 (57.1%)16 (50%)28 (52.8%)More than 2 comorbidities6 (28.6%)9 (28.1%)15 (28.3%)HistologieNHL low grade5 (23.8%)5 (15.6%)10 (18.9%)NHL High grade15 (71.4%)25 (78.1%)40 (75.5%)CLL1 (4.8%)2 (6.3%)3 (5.6%)Ann Arbor StageI000II2 (9.5%)2 (6.3%)4 (7.5%)III2 (9.5%)2 (6.3%)4 (7.5%)IV16 (76.2%)26 (81.3%)42 (79.2%)Previous chemotherapyNephrotoxic2 (9.5%)3 (9.3%)5 (9.4%)Non nephrotoxic17 (80.9%)21 (65.6%)38 (71.7%)Albumine blood level< = 305 (23.8%)5 (15.6%)10 (18.9%)LDH> N11 (52.4%)12 (37.5%)23 (43.4%)Total213253Table 2Renal Failures gradeR-DHAPR-DHAXNo renal failure13 (27.7%)100 (74.6%)Renal Failure34 (72.3%)34 (25.4%)(Reference 1: Group-based trajectory modeling in clinical research, Nagin et al. Annu Rev Clin Psychol. 2010) DisclosuresNo relevant conflicts of interest to declare.

CloB2A2 Reduced-Intensity Conditioning (RIC) Regimen Prior to Allogeneic Stem Cell Transplantation Provides Significant Better Survival Compared to FB2A2 RIC Regimen in Adults with Acute Myeloid Leukemia (AML): A Study on Behalf of the SFGM-TC

Purpose: The FB2A2 (fludarabine, intermediate doses of busulfan and ATG) reduced-intensity conditioning (RIC) regimen is considered as a standard RIC regimen in many centers worldwide. Recently, we have reported the prospective good results of a clofarabine-busulfan containing RIC regimen (CloB2A2) in adults with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in complete remission (CR) at time of transplant (Chevallier et al, Haematologica, 2014). Thus, this regimen may prove to be superior to the FB2A2 regimen in patients with AML/MDS.Patients and Methods:The aim of this study was to compare outcomes between adult AML/MDS patients who have received, between 2009 and 2015, in 26 French centers, either a FB2A2 RIC regimen (n=170, male 61%, median age: 58 years, AML 86%, CR1 79%) or the CloB2A2 RIC regimen (n=39, including the 16 cases treated within the prospective trial mentioned above, male 62%, median age: 61 years, AML 62%, CR1 64%). The FB2A2 and CloB2A2 regimens consisted of either 30 mg/m²/day Fludarabine for 5 days or 30mg/m²/day Clofarabine for 4 or 5 days, each combined with 3.2 mg/kg/day Busulfan for 2 days and 2.5 mg/kg/day Anti-thymocyte globulin (ATG, Thymoglobuline) for 2 days. As GVHD prophylaxis, cyclosporine (CsA) alone was used in case of related donor in both groups, and for the 16 CloB2A2 patients treated within the prospective trial, while CsA+ MMF were used in case of unrelated donors. The two groups were not statistically different in term of gender, median age and performans status at transplant, median white blood count at diagnosis, median time between diagnosis and transplant, type of donors or cytogenetics for AML patients. Conversely, there were more AML patients (86% vs 62%, p=0.0004) and more patients in CR1 (79% vs 64%, p=0.04) in the FB2A2 group. Also, CloB2A2 patients were transplanted more recently (median year of transplant: 2014 vs 2011, p<0.0001).Results: All patients engrafted, except one in the FB2A2 group. Median time of neutrophils recovery was similar between both groups (FB2A2: 17 days vs CloB2A2: 18 days, p=0.10). With a median follow-up of 28 and 14 months in the FB2A2 and the CloB2A2 groups, respectively, 2-year overall survival (OS) were 59% (51.4-66.7) for the former vs 77% (62.8-91.1) for the latter, p=0.07, 2-year leukemia-free survival (LFS) were 52.7% (44.9-60.4) vs 64% (48.1-79.9), p=0.23, 2-year relapse incidence were 31.1% (24.2-38.4) vs 27.5% (14-42.9), p=0.58, 2-year non relapse mortality were 16.2% (5.8-31.3) vs 8.5% (2.1-20.7), p=0.26 and 2-year chronic GVHD were 13.8% (8.3-20.5) vs 23.9% (8.1-44.2), p=0.12. Incidences of grade 2-4 or grade 3-4 acute GVHD were similar between both groups: FB2A2 22% vs CloB2A2 23%, p=0.86,and 8% vs 3%, p= 0.31. In multivariate analysis, FB2A2 RIC regimen was significantly associated with lower OS and LFS (HR: 2.45; 95%CI: 1.08-5.55, p=0.03; and HR: 2.32; 95%CI: 1.12-4.79, p=0.02) contrary to CR1 status which was associated with significant higher survivals (HR: 0.48; 95%CI: 0.28-0.83, p=0.008 and HR: 0.42; 95%CI: 0.25-0.70, p=0.001). MDS (HR: 1.88; 95%CI: 1.03-3.43, p=0.03) and higher WBC at diagnosis (>median) (HR: 1.76; 95%CI: 1.10-2.82, p=0.01) were also significantly associated with lower LFS. However, when considering AML and MDS patients separately, benefit of CLOB2A2 RIC regimen appears to be restricted to AML patients (2-year OS FB2A2: 58.1% vs CloB2A2: 80.2%; HR: 2.45; 95%CI: 1.08-5.55, p=0.03; and 2-year LFS FB2A2: 53.6%, vs CloB2A2: 76.9%; HR: 2.32; 95%CI: 1.12-4.79, p=0.02).Conclusion: Thisretrospective comparison suggests thattheCloB2A2 RIC regimen can likely provide a higher survival compared to the use of a FB2A2 RIC regimen for AML patients. A prospective phase 3 randomized study is warranted. DisclosuresDeconinck:JANSSEN: Other: Travel for international congress; NOVARTIS: Other: Travel for international congress; ALEXION: Other: Travel for international congress; ROCHE: Research Funding; PFIZER: Research Funding; CHUGAI: Other: Travel for international congress; LFB loboratory: Consultancy. Mohty:Janssen: Honoraria; Celgene: Honoraria.

Prise en charge des patients de Performans Status 2 atteints d'un cancer bronchique non à petites cellules métastatique

The treatment of fit patients (performance status 0-1) with metastatic stage of non-small cell lung cancer is well codified and consists in a doublet of platinum salt, preferably cisplatin, and third generation agent. On the other hand, treatment of performans status 2 patients who represent a non-negligible proportion of the whole population of patients with metastatic non-small cell lung cancer, is not so well defined. A first difficulty is due to the heterogeneity of this group of patients, as performans status 2 may be due to the extent of the disease but also to comorbidities. Second, performans status 2 patients are excluded from most of the clinical trials since 15 years. Finally appreciation of a performans status 2 is quite difficult and sometimes not reproducible. Nevertheless, it seems that those patients beneficiate from a doublet of carboplatin plus a third generation agent. For patients with EGFR mutations, treatment with TKI are as efficacious as in performans status 0-1 patients with quick improvement of the general condition.

Prognostic Value of C-kit and VEGF Expression in Small Cell Lung Cancer

SESSION TITLE: Lung Cancer Treatment Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Lung cancer is the leading cause of cancer related death in the world. Small cell lung cancer (SCLC) is an aggressive form of lung cancer with poor clinical course. Despite using new technologies and chemotherapeutic agents, little progress has been made in prolonging survival in SCLC. Performans status (PS), stage, age, gender, number of metastatic sites, weight loss and biochemical variables, such as serum albumin, sodium, alkaline phosphatase, lactat dehidrogenase levels are used to define prognosis in SCLC. However investigations are going on for finding a beter prognostic marker. The C-kit protein, which has type 3 receptor tyrosine kinase activity has been implicated in the pathophysiology of many tumors, including SCLC. Vascular endothelial growth factor (VEGF) expression was also corrolated to an increased risk of metastatic disease and a worse survival due to the role of angiogenesis in SCLC. METHODS: In our study we aimed to evaluate VEGF and C-kit expression and relation between survival and clinical factors affecting the prognosis of 53 patients who were diagnosed with SCLC between January 2005- August 2010. The expressions of VEGF and C-kit were studied immonuhistochemically. RESULTS: The expression of VEGF was detected in 64,2% and the expression of C-kit was detected in 60,4% of the patients. The results showed that VEGF and C-kit expressions were not associated with prognostic factors and survival. A multivariate analysis was perfomed to evaluate independent prognostic role of age, weight loss, PS, serum albumin level and stage. This analysis indicated that PS (p=0.001) and serum albumin (p=0.032) level had independent prognostic value on overall survival. CONCLUSIONS: Although our results did not show any correlations we recommend that the prognostic value of VEGF and C-kit expressions, must be further investigated in prospective and large studies due to their role in pathogenesis. CLINICAL IMPLICATIONS: The role of VEGF and C-kit expressions as an important event in the pathogenesis of SCLC are still debated, and remain to be clarified whether this expressions are relevant for tumor growth and survival. Based on the available data reported in the literature, C-kit tyrosine kinase inhibitors and VEGF-targeting monoclonal antibody bevacizumab have substantial clinical benefits. As a result, to understand the prognostic value of VEGF and C-kit expressions new studies and large series needed. DISCLOSURE: The following authors have nothing to disclose: Gulen Topaloglu, Aydin Yilmaz, Funda Demirag, Yurdanur Erdogan, Sezgi Sahin Duyar, Ulkü Yilmaz No Product/Research Disclosure Information

Is standard dose appropriate in elderly non-small cell lung carcinoma (NSCLC) patients treated with erlotinib?

9537 Background: Given the median age of 70 years in patients (pts) presenting NSCLC, the impact of age on outcomes including efficacy and toxicity of erlotinib remains unclear. In the BR21 study, analysis of subgroup based on age have reported similar survival benefits of erlotinib compared with placebo; however, elderly pts (³ 70 years) had significantly more toxicity, and were more likely to discontinue treatment (Paul Wheatley-Price et al., J Clin Oncol 2008). Thus we hypothesized that elderly were more exposed than younger pts. Methods: All consecutive pts with advanced or metastatic NSCLC treated with erlotinib between 2010 and 2014 were eligible in this prospective cohort. Erlotinib concentrations in plasma were determined using high-performance liquid chromatography at Day 15 after treatment initiation. We compared dose-normalized concentrations between pts < or ³ 75 years old using the Mann-Whitney U test and the occurrence of acute grade ³ 2 adverse events (AE) or treatment modifications by Fisher’s test. AE reports were graded using the National Cancer Institute Common Terminology Criteria V4. Lean body mass was estimated using Janmahasatian’s equation. Results: Out of 55 pts, erlotinib plasma concentration was analyzed in 45 pts. Median age was 65.6 (range 25-83), and 14 pts were over 75 years old. Among these 45 pts, 58% were female, 93% had an adenocarcinoma subtype; 44% were never smoker. Eighty-six percent of the pts had a performans status at baseline ≤ 2. Elderly pts had significantly lower estimated lean body mass (36.6 kg vs 47.7 kg; p = 0.00038). Within 2 weeks, grade ³ 2 AE occurred in 20% of pts, and 28 % in elderly. In the subgroup of pts over 75 years old, there was a trend for higher dose-normalized concentration at day 15 (1923.3 mg/L vs 1380.9 mg/L; p = 0.07), and the difference was significant in pts older than 80 (7 pts; 2484.6 mg/L vs 1377.4 mg/L; p = 0.0074). Four pts > 75 years old had dose reduction or discontinuation versus 0 in younger pts (p = 0.014, CI95% [1.2532; infinite]). Conclusions: Elderly patients are susceptible to be overexposed to erlotinib at 150mg/day, resulting in increased acute toxicity and treatment discontinuation.

Bevacizumab Trough Concentration in Recurrent Glioblastoma Patients

Purpose: Predictive marker of bevacizumab activity is an unmet medical need. Our objective was to evaluate the trough concentration of bevacizumab in patients with recurrent glioblastoma and to analyze its potential association with patient characteristics and outcome. Methods: We retrospectively included patients with recurrent glioblastoma treated with bevacizumab and chemotherapy with available plasma collected before the second bevacizumab administration (residual time). Trough bevacizumab concentrations and antibodies against bevacizumab were quantified by enzyme linked immunosorbent assay (ELISA). Results: We included 21 patients with a median age of 63.4 years at bevacizumab initiation. Occurrence of antibody against bevacizumab was not observed. Median pre-cycle 2 trough concentration of bevacizumab was 87.1 μg/mL (range, 21.7 μg/mL -151.8 μg/mL). Trough concentration of bevacizumab was not correlated to patient age (p=.529), gender (p=.622), weight (p=.403), size (p=.871), Body Mass Index (p=.439), Karnofsky Performans Status (p=.988) and steroid intake (p=0.403). No correlation was found between trough bevacizumab concentration and response rate (p=.856). The highest tertile of trough bevacizumab concentration tended to be associated with poor progression-free survival (p=0.152), while no correlation was observed for overall survival. Conclusion: Evaluation of the trough concentration of bevacizumab during treatment for patients with glioblastoma is feasible and highly variable. Its prognostic value should be explored in prospective trial.

Superior sulcus non small cell lung carcinoma: retrospective analysis of 42 patients.

AimsRetrospective, monocentric analysis of localized superior sulcus non-small cell cancer (SS-NSCLC), article management.Materials and methodsBetween 2000 and 2010, 42 patients have been treated for a SS-NSCLC. Median age was 54.7 years (34.5-86.8). Nineteen tumors (45.2%) were stage IIB, 18 were stage IIIA (42.9%) and 5 were stage IIIB (11.9%). Twenty-two patients were treated by pre-operative radiotherapy or chemoradiotherapy, 20 received exclusive radiotherapy or chemoradiotherapy. Preoperative and exclusive median radiotherapy doses were 46 Gy (40–47 Gy) and 51.8 Gy (40–70 Gy), respectively. All patients treated with chemotherapy received at least platinum. Mean follow up was 44.1 months (0–128 months).ResultsLocal, loco-regional and metastatic relapses occurred in 11 (26.2%), 2 (4.8%) and 15 patients (35.7%), respectively. Most common metastatic site was cerebral (7 patients, 46.7%). Median disease-free survival (DFS) was 9.7 months (8.9-10.4). One-, 2- and 5- years DFS rates were 44%, 33% and 26.5%, respectively. No prognostic factor was identified.Median overall survival (OS) was 22.6 months (10.4-34.8). One-, 2- and 5- years OS rates were 61.9%, 44.9% and 30.1%, respectively. Univariate prognostic factors for OS were WHO (p = 0.027) and tumoral response (p = 0.05). In multivariate analysis, independent favorable prognostic factors were WHO 0–1 (p = 0.017; OR = 0.316 [CI95% 0.123-0.81) and complete response to treatment (p = 0.035; OR = 0.312 [IC95% 0.106-0.919]).ConclusionThis study highlighted that a good performans status and complete response to treatment are independent factors of OS, whatever the delivered treatment. Brain was the most common metastatic relapse site.

Évaluation du dépistage des cancers de la femme et du dépistage après 75 ans dans le département de la Loire

In France, there is an important interregional disparity concerning participation to cancer screening programs. The aim of this study was to assess oncologic screening practices in Loire, a French rural department, in women and in the elderly (over age 74 years). For this, two surveys were conducted. The first one was regarding screening for breast, cervical and colorectal cancer in women over age 18 years living in Loire. The second survey was regarding onco-geriatric screening through two questionnaires : one for the elderly and the other for general practitioner (GP) of the department, evaluating screening for breast, colorectal, prostate, cervical and lung cancer. One hundred sixty six women were included in the first investigation mean age of 47.6 years. Ninety three point six per cent were screening for breast cancer, 19% received Human Papilloma virus vaccine, 83.1% were screening by Papanicolau smear for cervical cancer and finally, 51.7% were screening for colorectal cancer, among the one entering screening program criteria. In the second survey, 44 patients and 28 GP were included. Thirty-eight point six per cent of patients over 74 years continue screening. Only 11.4% were reluctant to screening and in 80% because of anxiety du to the results. Among GP, 50 % continued screening on two major criteria : life expectancy and performans status. The present study shows heterogeneity of screening in this department both rural and working class and gives us a societo-medical photography.

EP-1150 Superior sulcus non small cell lung carcinoma: Retrospective analysis of 42 patients

Aims: Retrospective, monocentric analysis of localized superior sulcus non-small cell cancer (SS-NSCLC), article management. Materials and methods: Between 2000 and 2010, 42 patients have been treated for a SS-NSCLC. Median age was 54.7 years (34.5-86.8). Nineteen tumors (45.2%) were stage IIB, 18 were stage IIIA (42.9%) and 5 were stage IIIB (11.9%). Twenty-two patients were treated by pre-operative radiotherapy or chemoradiotherapy, 20 received exclusive radiotherapy or chemoradiotherapy. Preoperative and exclusive median radiotherapy doses were 46 Gy (40–47 Gy) and 51.8 Gy (40–70 Gy), respectively. All patients treated with chemotherapy received at least platinum. Mean follow up was 44.1 months (0–128 months). Results: Local, loco-regional and metastatic relapses occurred in 11 (26.2%), 2 (4.8%) and 15 patients (35.7%), respectively. Most common metastatic site was cerebral (7 patients, 46.7%). Median disease-free survival (DFS) was 9.7 months (8.9-10.4). One-, 2- and 5- years DFS rates were 44%, 33% and 26.5%, respectively. No prognostic factor was identified. Median overall survival (OS) was 22.6 months (10.4-34.8). One-, 2- and 5- years OS rates were 61.9%, 44.9% and 30.1%, respectively. Univariate prognostic factors for OS were WHO (p=0.027) and tumoral response (p=0.05). In multivariate analysis, independent favorable prognostic factors were WHO 0–1 (p = 0.017; OR = 0.316 [CI95% 0.123-0.81) and complete response to treatment (p = 0.035; OR = 0.312 [IC95% 0.106-0.919]). Conclusion: This study highlighted that a good performans status and complete response to treatment are independent factors of OS, whatever the delivered treatment. Brain was the most common metastatic relapse site.

Role Of Allogeneic Transplant In Poor Risk CLL Patients: A Long-Term Monocentric Experience In 39 Patients

BackgroundAllogeneic stem cell transplantation (SCT) remains the only curative option in poor risk chronic lymphocytic leukemia (CLL). Reduced intensity conditioning regimens (RIC) have improved outcome and enlarged number of patients eligible to SCT. However it is still controversial whether patient characteristics, CLL treatment, conditioning regimen or GVH prophylaxis influence the outcome. Here we present the analysis of our cohort of CLL patients who underwent RIC SCT. Patients and methodsThis is a retrospective single center study Primary endpoint was overall survival; secondary endpoints were cumulated incidence of relapse and non-relapse mortality. ResultsFrom 2000 to 2012, Thirty-nine patients with a sex ratio of 2 were transplanted. At time of transplantation, median age was 59 years (27-68), 82% patients displayed performans status (PS) of 0 and 20% had a comorbidity score ≥3. More than half patients (54%) were Fludarabine refractory and FISH 17p deletion was found in 10 out of 23 tested patients (43%). Median delay between diagnosis and transplant was 92 months (4-182). Patients received a median of 3 (1-9) prior therapies. Last treatment before transplant was fludarabine-based in 12 patients, alemtuzumab in 13, and other (RCHOP, R-Bendamustine, RDHAP) in 14. Median delay between the last treatment and transplantation was 2 months (1-33). At time of transplant, overall response rate was 82% including 33% complete response (CR). Four-color phenotypic MRD was negative (<10-4) in 9 patients (23%). Donor type was HLA matched relative for 22 patients, unrelated for 13 and cord blood for 4. Conditioning regimen varied according to protocols and donor. It consisted of fludarabine, busulfan and antithymocyte globulin in 21 patients, fludarabine, TBI and rituximab in 14 patients and fludarabine, cyclophosphamide and total body irradiation (TBI) in 4 and. Graft versus host disease (GVHD) prophylaxis was provided by cyclosporine alone in 54% patients, and cyclosporine and mycophenolate mofetil in 46%.After transplant, overall response rate was 90% with 17 patients evolving from partial response or stable disease to complete response and MRD was negative in 28/33 (85%) patients. Donor chimerism was performed for 27 patients, chimerism >90% was obtained in all patients except one, after a median of 90d (19-180) post transplant. Acute and chronic extensive GVHD occurred in 44% and 38% patients respectively.With a median follow-up of 59 months, median overall survival (OS) was 97 months, 2- and 5-years OS were 72% and 59% respectively. Fifteen patients died, 7 from GVHD, 4 from sepsis, 1 from CLL and 3 from other causes. 2- and 5-years cumulated incidences (CI) of non-relapse mortality (NRM) were 25.6% and 38.3% respectively. Three patients relapsed after transplant, 2 are still alive 82 and 98 months post-transplant. 2- and 5-years cumulated incidences of relapse were 2.8% and 6.8% respectively. In univariate analysis, disease status at transplant and number of prior therapies were significantly associated with better OS (p=0.0009 and p=0.03 respectively), whereas a trend to correlation between PS and OS was observed (p=0.063). In multivariate analysis, PS and achievement of CR or PR before transplant correlated significantly to OS (p=0.015 and p=0.05 respectively). Clearance of MRD before transplant perhaps suggested a better survival (p=0.158). ConclusionThis retrospective study highlights the ability of allogeneic transplant to improve OS in otherwise very poor prognosis CLL patients and deserve further investigations. Disclosures:Aurran-Schleinitz:Roche: Honoraria.