1610 Renal function in patients receiving chemotherapy: Impact on survival

Abstracts lead to discontinuation of endocrine therapy. Topical estrogen therapy can provide relief but leads to systemic absorption of estrogens and its safety after a diagnosis of breast cancer remains uncertain. We have developed a cocoa-butter based essential oil pessary (EOP) as a novel approach to manage the symptoms of urogenital atrophy (UA) in women post breast cancer diagnosis. Materials and Methods: 1g solid cocoa butter based EOP containing oils chosen for their anti-inflammatory and anti-microbial properties were developed The Christie NHS Foundation Trust. Women receiving endocrine therapy as a treatment for breast cancer, who were experiencing symptoms of UA despite use of a topical hormonal or non-hormonal therapy were offered treatment with the EOP. Patients initially inserted one EOP nightly for 6 of 7 nights for 8 weeks, with the frequency reducing once symptomatic improvement was seen. Vaginal dilators were often required and introduced from month 2 onwards as appropriate. Efficacy was assessed using an Activities of Daily Living (ADL) questionnaire and the Measure Yourself Medical Outcome Profile 2 (MYMOP2) whereby patients chose their own symptoms of concern and score them from 0 to 6. Results: 23 women were treated between March 2012 and November 2014 for whom 2 month FU data were available. Of these 17 have completed 3 month follow up questionnaires. The majority (78%) were post-menopausal (age range 32−72 years). 56% (13 of 23) were receiving treatment with an aromatase inhibitor at the time of inclusion and 13% (3 of 23) tamoxifen. 20 women (87%) had previously received topical treatments for UA. 14 (61%) had a history of gynaecological/urinary infections. Primary symptoms reduced from a baseline median of 5 to a median at 8 weeks of 3 (p < 0.01, Wilcoxon signed rank test). Secondary symptoms scores and those of activity and wellbeing were evaluable in 16, 15 and 20 patients respectively and all demonstrated significant improvements (p < 0.01). The most common symptom using the MYMOP and ADL questionnaire was difficulty with sexual intercourse. 12 patients reported this to be an impossible activity at baseline, improving to 7 patients after only 2 months of treatment. No adverse events were reported and patient acceptance was universal. Conclusions: EOPs appear to offer women suffering from UA as a consequence of treatment for breast cancer a useful alternative therapy to vaginal moisturisers and topical estrogens. Large scale manufacture of the EOPs (Evamid® ), in GMP conditions, is now underway which will enable formal testing in a planned clinical trial programme. No conflict of interest.

1609 POSTER Final results from PAVES, a phase 3, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab for locally advanced or metastatic colorectal cancer (LA/mCRC) (NCT00911170) T. Pinter1 , P.K. Morrow2 , A. Cesas3 , A. Croitoru4 , J. Decaestecker5 , P. Gibbs6 , Y. Hotko7 , J. Jassem8 , G. Kurteva9 , J. Novotny10 , S. O’Reilly11 , T. Salek12 , L. Khosrowshahi13 , M. Reiner13 , Z. Klippel2 , C. Blanke14 . 1 Petz Aladar Teaching Hospital, Department of Oncoradiology, Gyor, Hungary; 2 Amgen Inc., Clinical Development, Thousand Oaks, USA; 3 Klaipeda University Hospital, Department of Oncology Chemotherapy, Klaipeda, Lithuania; 4 Fundeni Clinical Institute, Department of Medical Oncology, Bucharest, Romania; 5 AZ Delta Hospital, Oncology, Roeselare, Belgium; 6 The Western Hospital, Department of Oncology, Victoria, Australia; 7 Uzhgorod National University, Department of Oncology and Radiology, Uzhgorod, Ukraine; 8 Medical University Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland; 9 SHAT Oncology Sofia, Department of Chemotherapy, Sofia, Bulgaria; 10 Institut Onkologie a Rehabilitace na Plesi, Onkologie, Nova´ Ves pod Pleˇs´ı, Czech Republic; 11 Ireland Co-operative Oncology Research, ICORG, Dublin, Ireland; 12 National Cancer Institute, Department of Clinical Oncology, Bratislava, Slovak Republic; 13 Amgen Inc., Global Biostatistical Sciences, Thousand Oaks, USA; 14 Oregon Health & Sciences University, Knight Cancer Institute, Portland, USA Background: The incremental infection risk of adding bevacizumab to chemotherapy (ctx) and pegfilgrastim’s role in reducing this risk are not well understood. PAVES evaluated efficacy of pegfilgrastim in reducing febrile neutropenia (FN) in pts with LA/mCRC receiving first-line FOLFOX + bevacizumab or FOLFIRI + bevacizumab. PAVES met its primary endpoint; pegfilgrastim significantly reduced grade 3/4 FN incidence in the first 4 treatment (tx) cycles (placebo: 5.7% [95% CI: 3.7−8.3], pegfilgrastim: 2.4% [1.1−4.3], odds ratio [OR] 0.41, P = 0.014). Secondary endpoints prospectively assessed effect of pegfilgrastim on tumor-related outcomes. Here we present final results for objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) from PAVES.

S241 Material and Methods: Tx-na¨ıve pts 18 yrs with LA/mCRC measurable per RECIST 1.1 were randomly assigned 1:1 to placebo or 6 mg pegfilgrastim (Neulasta® ) ~24 h after ctx + bevacizumab. The study-tx period included 4 Q2W cycles, but pts could continue on assigned tx until progression. Pts who remained on study after the tx period were followed at regular intervals for up to 60 months (mo), and data on tumor and survival status were collected during the follow-up. The Cochran-Mantel-Haenszel test was used to test differences between tx groups for ORR and the Cox proportional hazard model was used to estimate hazard ratios (HRs) for OS and PFS. Results: 845 pts were randomized (Nov 2009 to Jan 2012); 422 to pegfilgrastim, 423 to placebo. Median age was 61 yrs. 512 (61%) pts were male; 819 (97%) had metastatic disease; 574 (68%) had colon cancer; 414 (49%) received FOLFOX; 431 (51%) received FOLFIRI. 774 (92%) pts completed 4 cycles of ctx + bevacizumab. By Mar 2, 2015 (database lock), median follow-up was 21.4 mo (21.5, pegfilgrastim; 21.4, placebo). See table for ORR, PFS, and OS results. Subgroup analyses of outcomes by ctx received (FOLFOX vs FOLFIRI) are ongoing. Conclusions: PAVES is the largest randomized trial that has prospectively evaluated effect of pegfilgrastim on treatment outcomes. No significant differences in ORR, PFS, and OS were observed between the pegfilgrastim and placebo arms, suggesting that pegfilgrastim does not negatively impact tumor response or survival in this pt population. Endpoint

Pegfilgrastim (n = 422)

Placebo (n = 423)

Pegfilgrastim vs Placebo

ORR (95% CI)

256/420a ; 61.0% (56.1–65.6)

242/420a ; 57.6% (52.7–62.4)

Diff = 3.3% (−4.5−11.2); ORb = 1.15 (0.87−1.51);

Median PFS (95% CI), mo

10.6 (9.4–11.2)

10.4 (9.5–11.1)

Median OS (95% CI), mo

24.0 (21.6–26.3)

23.1 (21.2–24.6)

P = 0.330 HRc = 0.93 (0.80−1.07); P = 0.300 HRc = 0.94 (0.81−1.10); P = 0.440

a Measurable disease. b Not adjusted for randomization stratification factors. c Adjusted for randomization stratification factors.

Conflict of interest: Ownership: Phuong Khanh Morrow (Amgen), Maureen Reiner (Amgen), Zandra Klippel (Amgen). Other Substantive Relationships: Adina Croitoru (lecture fee and research support, Amgen). Lynn Khosrowshahi (contractor to Amgen). 1610 POSTER Renal function in patients receiving chemotherapy: Impact on survival C. Thibault1 , D.K. Duong1 , F. Scotte1 , B. Rance2 , A. Bouchouicha2 , S. Oudard1 , R.T. Elaidi1 . 1 European Hospital Georges Pompidou, Medical Oncology, Paris, France; 2 European Hospital Georges Pompidou, Department of informatics, Paris, France Background: Renal impairment is known to be associated with a poor prognosis in cancer patients (pts). However, few studies have analyzed the evolution of renal function (RF) during treatment and it is a potential impact on overall survival. Methods: Clinical and biological data of pts treated with chemotherapy (CT) in ambulatory CT unit in European Georges Pompidou Hospital were prospectively collected between 2008 and 2014 as part of an oncologymonitoring program. We extracted clinical and biological data (creatinine) of pts treated for an advanced cancer. All values of creatinine were collected and RF was assessed by clearance of creatinine according to CockcroftGault formula. Impact of RF on OS was evaluated using 2 methods: Cox model and a longitudinal analysis k-means clustering model (KML) using all values of creatinine available during a period of 6 months after the beginning of CT. A multivariate analysis was conducted after adjusting for age and type of tumor. Results: 500 pts were included. Median age was 64 (35−87). The types of cancer were: lung (27%), urogenital (27%), breast (17%), gynecological (15%) and head and neck (14%). 25% pts had a creatinine clearance <60mL/min at baseline. In univariate and multivariate analyzes, RF at baseline was not associated with OS, neither using clearance of creatinine as a continuous variable nor using a threshold of 60 mL/min. However, after clustering pts in 3 or 4 groups according to RF evolution during a period of 6 months, RF was associated with OS (Table 1): – 3 clusters = mOS of each cluster: 41.7 m (22.8-NR), 30.6 m (17.1–41.2), 15.8 m (12.9–25.6) (log-rank=0.025) – 4 clusters = mOS of each cluster: 41.7 m (22.8-NR), 25.6 m (15.8–39.4), 24.2 m (13.1–41.2), 13.0 m (9.8–19.0) (log-rank=0.036) Conclusion: In our study, baseline RF had no impact on OS of pts treated with CT for a metastatic cancer. However, longitudinal analysis of RF during a period of 6 months was correlated with OS. These results suggest that

S242

Abstracts

longitudinal data of RF rather than baseline RF might be more appropriate to discriminate patients with different prognosis. Renal function

Cox model

At baseline At baseline (<60 vs >60 ml/min) KLM, first 6 mo 3 groups: C (150 mL/min) A (90 mL/min) B (60 mL/min) 4 groups: D* (150 mL/min) A* (100mL/min) B* (70 mL/min) C* (45 mL/min)

Univariate analysis

Multivariate analysis

HR

p

HR

p

1.15 (1.02–1.29) 1.25 (0.97−1.6)

0.046 1.07 (0.83–1.47) 0.088 1.05 (0.8–1.39)

0.32 0.71

B/C: 2.19 (1.18–4.07) A/C: 1.64 (0.88–3.05)

0.012 B/C: 2.07 (1.07−4.0) 0.122 A/C: 1.65 (0.87–3.13)

0.03 0.125

C*/D*: 2.61 (1.33–5.12) 0.005 C*/D*: 2.87 (1.35–6.05) 0.006 B*/D*: 1.78 (0.90–3.20) 0.079 B*/D*: 1.74(0.89–3.37) 0.104 A*/D*: 1.70 (1.33–5.12) 0.099 A*/D*: 1.82 (0.94–3.55) 0.077

No conflict of interest. 1611 POSTER Safety and efficacy of biosimilar filgrastim in patients with colorectal cancer undergoing neutropenia-inducing chemotherapy: A sub-analysis of the NEXT study ˆ D. Kamioner1 , S. Lepretre ˆ 2 , F. Maloisel3 , C. Berthou4 , H. Albrand5 . 1 Hopital Prive´ de l’Ouest Parisien, Oncologie, Trappes, France; 2 Henri Becquerel ´ Hospital, Hematology, Rouen, France; 3 Sainte-Anne Clinic, Hematologie ˆ ´ et d’Oncologie, Strasbourg, France; 4 Hopital Morvan, Hematologie, Brest, 5 France; Hospira France, Hospira, Meudon La Fort, France Background: Febrile neutropenia (FN) is a frequent and often serious complication of cytotoxic chemotherapy (CT). Biosimilar filgrastim (Nivestim™ , Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of FN and infection induced by myelosuppressive CT. The NEXT (Nivestim™ safety profile in patiEnts [pts] treated with cytotoXic CT in real-life clinical pracTice) study aimed to assess the safety of biosimilar filgrastim in pts undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as prophylaxis (ppx), or as curative treatment. Materials and Methods: NEXT was a prospective, non-interventional, longitudinal, multicentre study conducted in France to evaluate the FN and infection incidence as well as the safety of biosimilar filgrastim. Pts were monitored for 1−6 CT cycles with three visits at inclusion, during treatment and following CT. In the sub-analysis we assess the use of biosimilar filgrastim in pts with colorectal cancer. Results: Out of 2114 pts enrolled in the NEXT study, 197 pts undergoing cytotoxic CT for colorectal cancer and receiving biosimilar filgrastim as ppx (95.4%) or curative treatment (4.6%) were included in the sub-analyses. Ppx was mostly given as primary ppx (94.7%). At baseline, 54.8% of pts were male. Of the pts included in this cohort, 49.7% of pts had T3 stage tumours, while metastases were identified in 66.8% of pts. Adverse events (AEs) were reported in 19.3% of all pts and the most common AEs (occurring in >2% of pts who had AEs) were muscle and/or bone pain, diarrhoea, nausea, headaches, ‘other’ and vomiting. No FN or infection occurred in pts receiving biosimilar filgrastim as secondary ppx. FN, but no infections, occurred in 1.1% of pts given primary ppx. CT cycles were delayed due to FN in 10.2% of prophylactic pts and CT dose reductions occurred in 5.9% of prophylactic pts (n = 187). Overall, 1.7% of prophylactic pts with colorectal cancer had a high risk of developing FN (intermediate risk: 49.4%; low risk: 48.9%), according to the 2010 NCCN guidelines. Conclusion: Biosimilar filgrastim was well tolerated and effective in preventing FN and infection in pts receiving cytotoxic CT for colorectal cancer. AEs occurred in fewer than 20% of pts, with no pts who received biosimilar filgrastim as primary ppx experiencing FN and no prophylactic pts experiencing infections during the course of the study. The majority of patients who received biosimilar filgrastim had a low or intermediate risk of developing FN. Conflict of interest: Corporate-sponsored Research: FM has received research funding from Amgen, Hospira, Pfizer and Novartis. The NEXT study was supported by Hospira SAS. Medical writing assistance was provided by apothecom scopemedical ltd and funded by Hospira SAS. Other Substantive Relationships: HA is employed by Hospira SAS.

1612 POSTER Early venous thromboembolism is associated with worse prognosis in advanced pancreatic cancer M.L. Sanchez ´ Lorenzo1 , S. Garc´ıa Adrian ´ 2 , E. Mart´ınez de Castro3 , 4 M. Salgado Fernandez ´ , P. Mart´ınez del Prado5 , J.D. Cumplido Buron ´ 6, 9 I. Garc´ıa Escobar7 , J. Mart´ınez Galan ´ 8 , A.I. Ferrer Perez ´ , M. Lobo de Mena10 , M. Muniz ´ Olmos11 , ˜ Castrillo3 , C. Gonzalez Rivas8 , V. Pachon P. Jimenez ´ Fonseca1 , A.J. Munoz ˜ Mart´ın12 . 1 Hospital Universitario Central de Asturias, Medical Oncology Service, Oviedo, Spain; 2 Hospital ´ Universitario de Mostoles, Medical Oncology Service, Madrid, Spain; 3 ´ de Valdecilla, Medical Oncology Service, Hospital Universitario Marques 4 Santander, Spain; Hospital Santa Mar´ıa Nai, Medical Oncology Service, 5 Ourense, Spain; Hospital Universitario de Basurto, Medical Oncology Service, Bilbao, Spain; 6 Hospital de Torrevieja, Medical Oncology Service, ´ Torrevieja, Spain; 7 Hospital San Pedro de Alcantara, Medical Oncology ´ Service, Caceres, Spain; 8 Hospital Universitario Virgen de las Nieves, Medical Oncology Service, Granada, Spain; 9 Hospital Obispo Polanco, Medical Oncology Unit, Teruel, Spain; 10 Hospital General Universitario Gregorio Maranon, Medical Oncology Service, Madrid, Spain; 11 Hospital ´ y Cajal, Medical Oncology Service, Madrid, Spain; Universitario Ramon 12 ´ Medical Oncology Hospital General Universitario Gregorio Maran˜ on, Service, On behalf SEOM Cancer and Thrombosis Working Group, Spain Background: Recently, eVTE have been associated with worse prognosis in patients with lung cancer. Exocrine pancreatic cancer (EPC) is associated with the highest rates of VTE. Material and Methods: We performed a retrospective chart review to determine if eVTE (<3 months from cancer diagnosis) might carry a worse prognosis in metastatic EPC compared to late venous thromboembolism (lVTE), >3 months. 338 consecutive patients, attended in eleven hospitals of the Cancer & Thrombosis Working Group of the Spanish Society of Medical Oncology (SEOM), who were diagnosed and received chemotherapy for metastatic EPC from January 2008 through December 2011 were identified and included in the analysis. Results: VTE was identified in 100 (25.8%) patients after a median followup of 6.0 months (range 0.2–67.6). eVTE: 49%; lVTE: 51%. Incidentally diagnosed: 49% eVTE vs 58% lVTE, p = 0.333. Clinical characteristics: Table 1. Type of first event eVTE/lVTE: 18/10 deep vein thrombosis, 7/10 pulmonary embolism, 22/12 visceral vein thrombosis, other VTE 2/4, 10/5 simultaneous different events. lVTE patients: 3−6 months after diagnosis 19 patients, 6−12 months 10 patients and >12 months 12 patients. Patients with an eVTE had worse overall survival (OS) when compared to patients with lVTE (median OS 5.2 months vs. 11.5 months, p = 0.0002). Table 1.

Age (years), median (range) Gender, n (%) Male Female ECOG, n (%) 0−1 2 Unknown Pancreatic cancer location, n (%) Head Body Tail Overlapping Unknown Previous VTE, n (%) Previous arterial thromboembolism, n (%) Port-a-cath, n (%)

eVTE (N = 59, 15.2%)

lVTE (N = 41, 10.6%)

No VTE (n = 288, 74.2%)

66.5 (43.4–78.6)

63.9 (35.5–82.1)

64.9 (31.6–84.0)

30 (50.9%) 29 (49.1%)

16 (39.0%) 25 (61.0%)

183 (63.5%) 105 (36.5%)

38 (64.4%) 20 (33.9%) 1 (1.7%)

33 (80.5%) 8 (19.5%) 0

197 (68.4%) 83 (28.8%) 8 (2.8%)

14 (23.7%) 18 (30.5%) 20 (33.9%) 5 (8.5%) 2 (3.4%) 3 (5.1%) 8 (13.6%) 15 (25.4%)

23 (56.1%) 6 (14.6%) 8 (19.5%) 3 (7.3%) 1 (2.4%) 1 (2.4%) 2 (4.9%) 13 (31.7%)

146 (50.7%) 41 (14.2%) 47 (16.3%) 41 (14.2%) 13 (4.5%) 11 (3.8%) 30 (10.4%) 47 (16.3%)

Conclusions: The impact of VTE in OS is significantly higher in patients with eVTE compare to lVTE. Our findings suggest that only eVTE could be associated to worse prognosis in advanced EPC. No conflict of interest. 1613 POSTER Biosimilar filgrastim in the treatment and prevention of chemotherapy-induced neutropenia in patients with breast cancer: A sub-analysis of the NEXT study ˆ ˆ 2 , F. Maloisel3 , C. Berthou4 , H. Albrand5 . 1 Hopital D. Kamioner1 , S. Lepretre Prive´ de l’Ouest Parisien, Oncologie, Trappes, France; 2 Henri Becquerel ´ Hospital, Hematology, Rouen, France; 3 Sainte-Anne Clinic, Hematologie ˆ ´ et d’Oncologie, Strasbourg, France; 4 Hopital Morvan, Hematologie, Brest, 5 France; Hospira France, Hospira, Meudon La Foret, France Background: Febrile neutropenia (FN) is a major risk factor for infectionrelated morbidity/mortality as well as a dose-limiting toxicity in patients (pts) undergoing chemotherapy (CT). Biosimilar filgrastim (Nivestim™ , Hospira