Background

Since publications highlighting the role of sarcopenia, weight loss (WL) is no longer the corner stone of malnutrition assessment. An international consensus proposed in 2011 a definition and a staging of CAX, mainly based on WL, sarcopenia, inflammation and anorexia (Fearon). We initiated this study to fill the gap of epidemiological data on CAX in NSCLC in France and Belgium.

Methods

This cross-sectional, prospective, multicentric study was conducted in Patients (pts) with NSCLC regardless of the tumor stage and the treatment line. Skeletal muscle mass (SMM) was assessed by analyzing L3 CT-scan image. Pts completed Anorexia/CAX subscale of FAACT and EORTC QLQ-C30 health related quality of life (QoL) questionnaires. Primary endpoint was the frequency of CAX according to Fearon criteria. Secondary endpoints were the frequency and the characteristics of the other stages of CAX focusing on early and discrete malnutrition changes (pre-CAX).

Results

539 NSCLC pts were recruited within 3 months in 2016 by 56 sites, analysis population was of 531 pts and 312 had SMM assessment. Median age was 66 years, 66.5% were males, 79.9% were PS < 2, and the tumor stage was mainly IIIB-IV (87.3%). 38.7% of pts had CAX, 33.8% pre-CAX and 0.9% refractory CAX. CAX was associated with molecular tumor profiles: 23.9% in patients EGFR, ALK, ROS1, BRAF or HER2 positive, 41.4% in K-RAS+ and 43.2% with no molecular abnormality (p = 0.003). Interestingly, the more advanced the CAX stage is, the poorer the score of functional scale (except cognitive) of the QoL questionnaire (p < 0.0001). Sarcopenia was present in 66.7% of CAX pts and 68.5% of pre-CAX pts (all without WL or WL ≤ 2%). Notably, 25.8% of pre-CAX pts had only sarcopenia with limited WL (≤2%) and no anorexia (questioning the mechanisms of sarcopenia). In pts with limited WL (≤2%), the loss of appetite was associated with sarcopenia in 44% of the cases.

Conclusions

This is the first study showing an association between molecular abnormality in NSCLC and cachexia. It has also shown that it may be useful to detect sarcopenia in pts with limited WL (<2%), especially in those with loss of appetite. Cachexia stages were associated to functional QoL items.

Clinical trial identification

NCT02968979, First received: November 17, 2016

Legal entity responsible for the study

Chugai Pharma France

Funding

Chugai Pharma France

Disclosure

D. Debieuvre, P-J. Souquet, S. Antoun: Corporate-sponsored research: Chugai-Pharma France. H. Morel: Corporate-sponsored research: Chugai Pharma France, Roche, Astra, Lilly, MSD, Pfizer, BMS, amgen. V. Surmont: Corporate-sponsored research: Chugai-Pharma France. D. Planchard: Corporate-sponsored consultancy: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Pfizer, Roche, Novartis, Chugai Pharma France. F. Bonnetain: corporate-sponsored research: Chugai Pharma France, Amgen, Roche, Merck Serono, Nestlé, Ipsen, Jansen. I. Krakowski: Membership on an advisory board and/or symposium: Chugai Pharma France, Kyowa kirin, Pfizer, Astellas, Janssen, Takeda, P Fabre. H. Gaudin: Employee of Chugai Pharma France.

Background

Cancer patients undergoing chemotherapy suffer from nausea, vomiting, low blood counts and electrolyte disturbances that impose stress on the nutritional needs of cancer patients. Nutritional status has been shown to reflect not just the patient’s general condition but also to predict patient survival. In this study, we evaluate the predictive effects of pre-chemotherapy nutritional status in patients with solid malignancies on chemotherapy response and quality of life.

Methods

Two hundred adult patients with localized solid malignancies (Except GI and Brain malignancies) undergoing Neoadjuvant/adjuvant chemotherapy were analyzed for their nutritional status before the therapy. Nutritional status was assessed using Subjective Global assessment (SGA), Nutritional risk index (NRI), Body mass Index (BMI), Platelet lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and Albumin-globulin ratio (AGR) prior to their chemotherapy treatment. Patients were also assessed for Hand grip strength, Quality of life using Functional assessment of Chronic illness Therapy (FACIT) and EUROQol C30 and radiological response using RECIST criteria following chemotherapy.

Results

Mean age of study population was 51.65 ± 10.1years. Multivariate regression analysis was done on Chemotherapy outcomes such as Response criteria, FACIT scores, Quality of life scores and handgrip strength using, SGA, NRI, NLR, BMI and Albumin/Globulin ratio as predictors. SGA score emerged as a significant primary predictor for hand grip strength (β=-7.3, p < 0.001) followed by BMI (β = 1.3, p < 0.001) and NRI (β=-0.73, p < 0.001). SGA emerged a significant primary predictor for FACIT score (β = 16.1, p < 0.001) followed by NLR (β=- 0.43, p = 0.008). SGA emerged as a significant primary predictor for physical activity (β = 1.73, p < 0.001) followed by BMI (β=-0.19). SGA emerged as a significant predictor of quality of life score (β=-3.13, p < 0.001). Multinomial logistic regression for a complete response to RECIST criteria showed lower NLR to be a significant predictor (β = 0.90, p = 0.04).

Conclusions

The results suggest that pre-chemotherapy nutritional status and NLR influence the functional quality of life, strength and chemotherapy response in patients with solid malignancies.

Legal entity responsible for the study

Raghavendra Rao M

Funding

HCG Foundation

Disclosure

All authors have declared no conflicts of interest.

Background

The GAND-emesis trial, a multinational, randomised, double-blind, placebo-controlled phase III trial, in women with cervical cancer receiving fractionated radiotherapy and weekly cisplatin 40 mg/m², demonstrated an increase of 17% in the proportion of patients completing five weeks of treatment without vomiting when fosaprepitant (FOS) was added to palonosetron (PAL) and dexamethasone (DEX) (Ruhlmann et al, Lancet Oncol, 2016). As a secondary endpoint we investigated whether there was any difference in impairment of daily functional life between groups as a result of nausea or vomiting.

Methods

The validated Functional Living Index – Emesis (FLIE) questionnaire consists of 18-items to measure the impact of nausea (9 items domain) and vomiting (9 items domain) on daily functional life. The FLIE-questionnaire was completed at baseline and again at end of study (EoS). The scores for each domain and the total score were calculated according to the FLIE Manual. Domain scores ≥ 54 and total score ≥ 108 indicate no or minimal impact on daily life. The Kruskal-Wallis H test was used to test the difference between groups.

Results

Two hundred and thirty-four patients from four countries were randomised and received study medication. Nine patients were excluded due to invalid questionnaires. Included were 115 patients receiving FOS and 110 patients receiving placebo (PLA). The point scores at baseline were similar across groups (FOS vs PLA); nausea domain: 59.9 vs 60.3 (p = 0.31); vomiting domain: 61.9 vs 62.1 (p = 0.16); and total score: 121.8 vs 122.4 (0.37). At EoS, a statistically significant difference was demonstrated for the point scores for the nausea domain and the total score (FOS vs PLA); nausea domain: 54.9 vs 53 (p = 0.02); vomiting domain: 61.4 vs 60.9 (p = 0.10); and total score: 116.3 vs 113.9 (p = 0.01).

Conclusions

This is the first study to investigate safety, efficacy, and impact on daily function of a neurokinin-1 receptor antagonist during the entire course of concomitant chemo-radiotherapy. The addition of FOS to PAL and DEX not only improved emetic control but also gave a clinically and statistically significant reduction of the impact of nausea on patients’ daily functional life.

Clinical trial identification

EudraCT number: 2009-014691-21. ClinicalTrials.gov: NCT 01074697.

Legal entity responsible for the study

Sponsors delegate and coordinating investigator Christina H. Ruhlmann/for sponsor Prof. Jørn Herrstedt, Odense University Hospital

Funding

unrestricted grants from Biovitrum and Helsinn Healthcare S.A.

Disclosure

F. Hilpert: Grants from Riemser Pharma during the conduct of the study. P. Feyer: Grants from Riemser Pharma during the conduct of the study; advisory consultant for MSD, outside the submitted work. D. Keefe: Grants from Helsinn, other from Merck, outside the submitted work J. Herrstedt: Unrestricted grant from Helsinn Healthcare, and an unrestricted grant from SOBI, during the conduct of the study; personal fees from Tesaro outside the submitted work. All other authors have declared no conflicts of interest.

Background

A debate on health-related quality of life (HRQoL) by patients’ assessment and the assessment of toxicity by physicians in clinical trials is ongoing. The relations between these two assessments is therefore of importance. The aim of this study was to investigate the relations between toxicity items (Common Terminology Criteria for Adverse Events, version 3.0.) and items in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Methods

Data was collected in a randomised phase 3 trial, comparing dose dense vs standard administration of adjuvant chemotherapy in high-risk breast cancer patients with mostly node positive disease (Foukakis et al., 2016). Data from the assessment at the end of treatment was used. Items from the EORTC QLQ-C30, considered to be associated with CTCAE, were chosen individually by three researchers. Relations based on ordinal data were analysed by Goodman and Kruskal gamma.

Results

A total of 1428 event-free patients were included. Relations between 13 toxicities and 36 EORTC QLQ-C30 items (some with more than one toxicity) were investigated.Table:

1422O Strong or moderate relation between toxicity and HRQoL item

Conclusions

Few relations were found between CTCAE and HRQoL items, indicating that CTCAE does not mirror the total patient experience. Some toxicities, however, are not related to patients scoring of HRQoL and therefore have to be reported by physicians. These findings should raise concerns on how to best evaluate HRQoL/toxicities in clinical trials.

Clinical trial identification

NCT00798070 and ISRCTN39017665

Legal entity responsible for the study

Department of Oncology-Pathology, Karolinska Institutet

Funding

Swedish Cancer Society

Disclosure

T. Foukakis: Honoraria for lectures from Novartis, Pfizer, Roche and Eisai. Royalty from UpToDate. Institutional grant to the Karolinska University Hospital from Roche and Pfizer. M. Gnant: Institutional research support from AstraZeneca, Roche, Novartis, Pfizer. Lecture fees & honoraria for advisory boards from Roche, AstraZeneca, Celgene, Novartis, OBI-Pharma, Amgen. Consultant for Accelsiors. An immediate family member employed by Sandoz. G. von Minckwitz: Institutional research support from Pfizer, Sanofi, Amgen, Roche, Novartis, Celgene, Teva, AstraZeneca, Myriad Genetics, Abbvie, Vifor Pharma. N-O. Bengtsson: Advisory board Amgen Biosimilars for Trastuzumab. G. Steger: Lecture honoraria and travel support from Amgen and Roche. J. Bergh: Grants from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi-Aventis to Karolinska Institutet and University Hospital. No personal payments. Honoraria from UpToDate for a chapter in breast cancer diagnostics to Asklepios Medicine HB. All other authors have declared no conflicts of interest.

Background

Preclinical evidence suggests a possible negative impact of germline BRCA mutations on female fertility. However, the reproductive potential and performance of fertility-preserving procedures in BRCA+ BC pts remain largely uncertain. We aimed to assess fertility outcomes in BRCA+ BC pts who underwent oocyte cryopreservation (OC) or ovarian tissue cryopreservation (OTC) before (neo)adjuvant chemotherapy.

Methods

This was a retrospective analysis of two prospective single center studies investigating OC and OTC in early BC pts. The present analysis included known BRCA+ or BRCA mutation-negative (BRCA-) BC pts who underwent OC or OTC between January 2006 and December 2016. Pts with unknown BRCA status, BRCA variants of unknown significance or other germline mutations were excluded. Baseline anti-mullerian hormone (AMH), OC and OTC performance were compared between BRCA+ and BRCA- BC pts.

Results

Out of 98 pts included in this analysis, 29 were BRCA+ and 69 BRCA-. Median age was 31 (range: 29-33) and 30 (range: 28-33) years in BRCA+ and BRCA- BC pts, respectively. Baseline AMH was 1.8 ng/ml (range: 1-2.7) in BRCA+ and 2.6 ng/ml (range: 1.4-4.3) in BRCA- BC pts (p = 0.108). Among pts who underwent OC (n = 27), despite receiving a numerically higher dose of gonadotropins (2775 vs 2150 UI; p = 0.125) and longer duration of stimulation (11.5 vs 9; p = 0.164), BRCA+ pts tended to retrieve (6.5 vs. 10; p = 0.135) and to cryopreserve (3.5 vs 6; p = 0.134) less oocytes than BRCA- pts. Poor response rate (i.e. retrieval of ≤ 4 oocytes) was 40% in BRCA+ and 12.5% in BRCA- BC pts (p = 0.105). Among pts who underwent OTC (n = 71), BRCA+ pts had numerically lower oocyte density per fragment (0.08 vs 0.14; p = 0.224) and per mm2 (0.33 vs 0.75; p = 0.160) than BRCA- pts. Two BRCA+ pts were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1+ and BRCA2+ pts was observed in any of the above-mentioned outcomes.

Conclusions

This is the largest study addressing fertility issues in BRCA+ BC pts. We observed a trend for reduced reproductive potential and performance of OC and OTC in BRCA+ BC pts. Further research efforts in this field are urgently needed.

Clinical trial identification

Not applicable

Legal entity responsible for the study

CUB-Hôpital Erasme

Funding

None

Disclosure

E. De Azambuja, M. Ignatiadis: Honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work. All other authors have declared no conflicts of interest.