ESMO Sept. 2014

Topic: Supportive Care


1528P – Relationship between rest metabolism and performance status in cancer patients: a prospective study in 161 patients

C. Vazeille, J. Durand, N. Neveux, A. Cessot, P. Boudou-Rouquette, A. Jouinot,  J. Alexandre, L. Cynober, F. Goldwasser

Relationship between rest metabolism


The WHO Performance Status (PS) of cancer patients (pts) correlates with survival and with anticancer treatments tolerability. However, PS is subject to inter-observer variability and is not sensitive to detect pts with high-risk of treatment toxicity. We studied the relationship between Rest Metabolic Rate (RMR) and PS.


A prospective observational, monocentric study was conducted. Before treatment initiation, RMR was measured using indirect calorimetry (Fitmate®, Cosmed srl) and compared to estimated RMR obtained by the modified Harris and Benedict equation. Hypermetabolics (Hm) pts were defined as having measured RMR ≥110% of calculated RMR and Not Hypermetabolics (NoHm) pts <110%. We recorded (PS), weight loss, α-1 glycoprotein acid (α-1 GP)(1), CRP(2), ferritin, albumin(3), transthyretin(4), Nutritional and Inflammatory Status (NIS)=(1X2)/(3X4), daily caloric intakes (dci) and energetic gap. Comparisons between Hm and NoHm pts used t-test and chi2 test.


A total of 161 consecutive pts were analyzed : 58% males, median age : 64 years (20-94). Primary tumor: genito-urinary (23%) gastro-intestinal (20%), lung (17%); 10% were PS ≥3; median weight loss : 4.1% (-14.9–+18.5); mean energetic gap: +80 kcal/d; mean RMR : 1676 kcal/d; 60% of the pts were Hm with mean RMR= 1815 kcal/d vs 1433 kcal/d in NoHm pts (P<0.01). The percent of Hm pts increased with PS deterioration: 45% in PS1, 65% in PS2 and 85% in PS3-4 pts (p = 0.05). Hm pts had increased weight loss: weight loss of 6% vs 3% (t=3.47, p < 0.01); weight loss>5% in 52% vs 32% of the pts (p = 0.03). Hm pts had more inflammation: α1-GP 1.5 vs 1.1 g/L (t=3.41, p < 0.01); CRP 30 vs 17 mg/L (t=2.42,p = 0.03); ferritin 406 vs 245 µg/L (p < 0.01), NIS 14 vs 2.82 (t=2,19, p = 0.03). Mean energetic gap was -189 kcal/d in Hm vs +268 kcal/d in NoHm pts (t=-4.4, p < 0.01) while dci were equivalent: 1650 kcal/d for Hm and 1689 kcal/d for NoHm pts (p = 0.69).


Hypermetabolism may account for cancer-induced asthenia and development of cachexia. The measurement of RMR allows to detect pts at high-risk of malnutrition amongst pts with PS

Disclosure: All authors have declared no conflicts of interest.

Relationship between rest metabolism and performance status in cancer patients

Topic: Translational Research

251P – Prognostic value of pre-treatment neutrophil to lymphocyte ratio in patients (pts) with metastatic solid tumors: Results of an observational cohort from a single French center

Y. Vano, F. Scotte, P. Combe, A. Angelergues, M. Auvray, P. Leroy, E. Tartour, S. Oudard, R. Elaidi

poster esmo 2014 Y Vano


Pre-treatment Neutrophil to Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported as a prognostic factor in some metastatic solid tumors (mST). Whether the NLR prognostic value depends on primary tumor site (PTS) has never been investigated. This study aimed to assess the prognostic value of pre-treatment NLR in pts with various mST treated with chemotherapy.


Using the PROCHE program we included all metastatic pts with an available NLR before the start of chemotherapy in the Oncology day hospital of Georges Pompidou European Hospital between 2008 and 2011. The NLR value was used as a continuous variable. Primary endpoint was overall survival (OS) from start of chemotherapy until patient’s death/last contact. Results were adjusted with the following variables: Age, Eastern Cooperative Oncology Group Performance Status (PS) (0–1 vs. ≥2), and primary tumor site (PTS): breast (BC), lung (LC), urogenital (UG) ovarian (OC), head and neck (HNC) and others (O).


467 mST pts, median (range) age = 64y (16-91), sex-ratio = 1.5 were included. PTS were distributed as follows: LC = 137pts (29.3%), UG = 133pts (28.5%), HNC = 61 (13%), OC = 55 (11.8%), BC = 54pts (11.6%), and O = 27 (5.8%). PS ≤ 1 = 340pts (72.8%) and PS ≥ 2 = 127 (27.2%). Median (range) NLR was 2.43 (0.06-48.5). Continuous NLR at baseline was significantly associated with OS in univariate analysis: HR (for 1 standard deviation unit = 5.07) = 1.15 (95%CI = 1.04-1.27; p = 0.007). Comparison of last (T3) and first terciles (T1) of NLR (157 and 152 pts, respectively) revealed that OS was shorter for pts with the highest NLR: 12.3m (95%CI = 10.4-17.3) vs. 20m (95%CI = 16.0-28.5), HR (T3/T1) = 1.58, 95%CI = 1.17-2.12 (p = 0.003). The highest NLR remains independently correlated with a worse OS after adjustment in multivariate analysis (HR = 1.46 (95%CI = 1.07-1.98), p = 0.01), as well as OC localization (p = 0.015).


High pre-treatment NLR is an independent prognostic factor for mST pts treated with chemotherapy whatever the primary tumor site. These results must be validated prospectively.

Disclosure: Y. Vano: Pfizer, Novartis, GSK, Sanofi, Astellas: advisory board Sandoz, Teva: funding for observational studies. No conflicts of interest directly related to this study; S. Oudard: Consultant or Advisory Role: Bayer, Janssen, Novartis, Pfizer, Sanofi, Takeda Honoraria: Bayer, Janssen, Novartis, Pfizer, Sanofi, Takeda No financial interest related to this study; All other authors have declared no conflicts of interest.


Topic: Anti-Cancer Agents & Biologic Therapy – Non-Small Cell Lung Cancer, metastatic – Translational Research


1280P – Plasmatic tumor DNA assessments predict clinical outcome in EGFR-mutated non-small cell lung cancer patients treated by EGFR inhibitors


N. Pecuchet, A. Didelot, E. Zonta, C. Lours, L. Gibault, N. Rice, P. Laurent-Puig, E. Fabre, V. Taly, H. Blons

Poster Esmo 2014 Nicolas Pécuchet


We aimed to study the dynamics of plasmatic EGFR mutations by qualitative (Q-PCR) and quantitative (droplet PCR) methods in EGFR-mutated lung cancer patients treated by EGFR tyrosine kinase inhibitors (EGFR-TKI).


We investigated a single-institution cohort of patients treated by EGFR-TKI. Plasma blood samples and RECIST assessments were repeated every 2 months. Plasmatic cell-free DNA extraction was performed with the QIAsymphony DSP Virus/Pathogen kit (Qiagen). EGFR mutations were assessed in plasmatic DNA using Q-PCR and droplets digital PCR with CAST probes (L858R and Del19). The rate of EGFR mutant/wild-type droplets was used for normalization. The prediction of plasmatic DNA changes between two consecutive samples on treatment outcome was evaluated by Receiver Operator Characteristic (ROC). Survival was estimated with the Kaplan-Meier method.


22 EGFR-mutated patients treated by EGFR-TKI underwent plasmatic DNA follow-up. Patients were stage IV (n = 22), TKI naïve (n = 17), or TKI pre-treated (n = 5). Median follow-up, progression-free survival (PFS) and overall survival were 19.0, 4.7 and 15.8 months, respectively. At baseline, tumor plasmatic DNA was found by Q-PCR, droplets or one of the two technics in 14, 15 and 16/20 (80%) patients, respectively. Droplet changes under treatment were more accurate than bulk PCR changes to predict RECIST outcome (progressive disease vs. clinical benefit, ie stable disease or partial response): ROC area under the curve (AUC) 0.92 and 0.35, respectively. Droplet changes also predict 2-month RECIST outcome, ROC AUC 0.94. According to ROC Youden indexes, a droplets increase of +19% best predicts immediate (sensitivity 0.90, specificity 0.84) and 2-months RECIST outcome (sensitivity 0.88, specificity 0.96). Median PFS assessed by droplets was 3.4 months (cut off +19%). Mean time from droplets increase (cut off +19%) to RECIST progression was 42 ± 23 days.


In this feasibility cohort, droplets increase under EGFR-TKI predicts immediate and 2-month treatment outcomes. Plasmatic tumor DNA monitoring could anticipates the radiological tumor progression, allowing clinicians to change treatment before a symptomatic or lethal tumor progression occurs. The threshold of +19% droplets increase will be prospectively tested in an on-going biomarker trial.

Disclosure: N. Pecuchet: I received honorarium from Roche; P. Laurent-Puig: I received honorarium from RainDance; E. Fabre: I received honorarium from Roche and AstraZeneca; V. Taly: I received honorarium from RainDance. All other authors have declared no conflicts of interest.



Topic : Anti-Cancer Agents & Biologic Therapy – Colon Cancer – Translational Research


572P – Prognostic value of KRAS mutations in stage III colon cancer: post-hoc analyses of the PETACC8 Phase III trial

ESMO 2014 HB


H. Blons (Paris, France, J. Emile (Paris, France), K. Le Malicot (Dijon, France), A. Zaanan (Paris, France), J. Tabernero (Barcelona, Spain), E. Mini (Firenze, Italy), G. Folprecht (Dresden, Germany), J. Van Laethem (Brussels, Belgium), J. Thaler (WELS, Austria), J. Bridgewater (LONDON, United Kingdom), L. Petersen (København, France), E. Van Cutsem (Leuven, Belgium), C. Lepage (DIJON Cedex, France), R. Salazar (Barcelona, Spain), P. Laurent-Puig (Paris, France), J. Taieb (Paris, France)

The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined the prognostic impact of KRAS mutations in stage III patients receiving adjuvant FOLFOX +/- cetuximab from the PETACC8 Phase III trial.

KRAS exon2 mutations were examined in BRAF wild type tumours from patients enrolled in the PETACC8 trial. Because no effect from adjuvant cetuximab was reported, tumours from both study arms were pooled for analysis. Association between time to recurrence (TTR) and Disease-free survival (DFS) and KRAS mutation type was evaluated using Cox proportional hazard model.

KRAS mutations were found in 638/1657 tumours. KRAS mutations in codon 12 (HR: 1.67; 95% confidence interval [CI] [1.35-2.04]; P < 0.001) but not in codon 13 (HR: 1.23; 95% confidence interval [CI] [0.85-1.79]; P = 0.26) were significantly associated with shorter TTR as compared to patients with KRAS/BRAF wild-type tumours, independently of other covariates. Taking anatomic sites into account, the impact of KRAS mutations on TTR was only found for distal tumours (n = 1043; 692 wild type; 351 mutated) with an increased risk of relapse (HR: 1.96; 95% confidence interval [CI] [1.51-2.56]; P < 0.0001) for KRAS codon 12 mutated tumours and a trend for codon 13 (HR: 1.59; 95% confidence interval [CI] [1.00-2.56]; P = 0.051). Similar results were found for DFS.

KRAS exon 2 mutations are independent predictors of TTR for patients with stage III distal CC receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider tumour location and KRAS mutations as important stratification factors.

Disclosure: J. Emile: received Honoraria from Merck-Serono; J. Tabernero: declared research funding from, and providing advisory roles for Amgen Merck KGaA and Sanofi; G. Folprecht: declared research funding from Merck KGaA and homoraria (advisory boards lectures) from Merck KGaA Roche Lilly and Amgen; J. Thaler: declared research funding and honororio for lectures from Sanofi and Merck; J.A. Bridgewater: declared advisory roles fro Merck, Sanofi and Roche; L. Petersen: declared advisory roles for Roche and Bayer; E. Van Cutsem: declared receiving research funding from Merck Serono paid to his institution; R. Salazar: declared providing advisory roles and lectures for sanofi Merck KGaA and Amgen; P. Laurent-Puig: declared providing advisory roles and lectures for Sanofi, Merck serono, amgen, Roche, Genomic Health, Myriad Genetics, and Pfizer; J. Taieb: declared research fundings from, and providing advisory roles and lectures for Sanofi, Merck KgaA. All other authors have declared no conflicts of interest.