Weight loss and body mass index in advanced gastric cancer patients treated with second-line ramucirumab: a real-life multicentre study
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Aims and methods
This multicenter retrospective study aims to evaluate the correlations between Body Weight Loss (BWL), Body Mass Index (BMI) and clinical outcomes (ORR, PFS, and OS) of advanced gastric cancer (aGC) patients treated with second-line ramucirumab-based therapy in a “real-life” setting.
From December 2014 to October 2018, 101 consecutive aGC patients progressed to a first-line chemotherapy were treated with ramucirumab alone (10.9%) or in combination with paclitaxel (89.1%). Median BMI was 21.2 kg/m2 and mBWL since first-line treatment commencement was 4.5%. Among 53 patients who underwent primary tumor resection (PTR), 73.6% experienced BWL, while 26.4% did not experience BWL (p = 0.0429). Patients who underwent PTR had a significantly higher probability of experiencing BWL (yes vs no) [OR = 2.35 (95% CI 1.02–5.42), p = 0.0439]. Among the 89 evaluable patients, ORR was 26.9% (95% CI 17.2–40.1). At a median follow-up of 17.3 months, mPFS was 5.4 months (95% CI 3.6–6.8) and mOS was 8.7 months (95% CI 7.3–11.9). In the multivariate analysis, only ECOG-PS and BMI were confirmed independent predictors for shorter PFS [HR = 1.69 (95% CI 1.01–2.82), p = 0.04] [HR = 1.97 (95% CI 1.12–3.46), p = 0.01] and OS [HR = 1.69 (95% CI 1.01–2.83), p = 0.04] [HR = 2.08 (95% CI 1.17–3.70), p = 0.01].
Efficacy of ramucirumab is confirmed in this “real-life” analysis. BWL seems not to have correlations with clinical outcomes in these patients, while BMI and ECOG-PS remain major prognostic factors. A possible explanation for the lack of prognostic effect of BWL might be the proportion of patients subjected to PTR in this series (52.5%).
KeywordsAdvanced gastric cancer Ramucirumab Body mass index Body weight loss Prognostic factors Second-line chemotherapy
This work was supported by the Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO).
All authors contributed to the publication according to the ICMJE guidelines for the authorship. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work is appropriately investigated and resolved.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
Dr Alessio Cortellini received grants as speaker by MSD, Astra-Zeneca and Boehringer Ingelheim, gran consultancies by BMS, Roche, Novartis, Istituto Gentili and Ipsen.
All patients provided informed consent to participate in this observational non-interventional study.
The procedures followed were in accordance with the precepts of Good Clinical Practice and the Declaration of Helsinki. The study was conducted following the rules of the local bioethical committee competent on human experimentation (Comitato etico per le province di L’Aquila e Teramo).
- Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB et al (2016) Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 17(12):1697–1708CrossRefGoogle Scholar
- Aoyama T, Sato T, Maezawa Y, Kano K, Hayashi T, Yamada T et al (2017) Postoperative weight loss leads to poor survival through poor S-1 efficacy in patients with stage II/III gastric cancer. Int J Clin Oncol. 22(3):476–483. https://doi.org/10.1007/s10147-017-1089-y (Epub 2017 Feb 7)CrossRefGoogle Scholar
- Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A et al (2010) Trastuzumab in combination with chemoterapy versus chemoterapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open label, randomised controlled trial. Lancet 376(9742):687–697CrossRefGoogle Scholar
- Cortellini A, Cannita K, Parisi A, Venditti O, Lanfiuti Baldi P, De Berardis B et al (2018) Timed-flat infusion of 5-fluorouracil with docetaxel and oxaliplatin as first-line treatment of gastroesophageal adenocarcinoma: a single institution experience with the FD/FOx regimen. Oncol Rep 40(2):803–812. https://doi.org/10.3892/or.2018.6475 (Epub 2018 Jun 6)Google Scholar
- Cox DR (1972) Regression models and life tables (with discussion). J R Stat Soc (Series B) 74:187–200Google Scholar
- Ebinger SM, Warschkow R, Tarantino I, Schmied BM, Güller U, Schiesser M (2016) Modest overall survival improvements from 1998 to 2009 in metastatic gastric cancer patients: a population-based SEER analysis. Gastric Cancer 19(3):723–734. https://doi.org/10.1007/s10120-015-0541-9 (Epub 2015 Sep 21)CrossRefGoogle Scholar
- Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F et al (2014) Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer 50(7):1330–1344. https://doi.org/10.1016/j.ejca.2014.01.029 (Epub 2014 Mar 17)CrossRefGoogle Scholar
- Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C et al (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31–39CrossRefGoogle Scholar
- Fuchs CS, Muro K, Tomasek J, Van Cutsem E, Cho JY, Oh SC et al (2017) Prognostic factor analysis of overall survival in gastric cancer from two phase III studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data. J Gastric Cancer. 17(2):132–144CrossRefPubMedCentralGoogle Scholar
- Janmaat VT, Steyerberg EW, Van Der Gaast A, Mathijssen RH, Bruno MJ, Peppelenbosch MP et al (2017) Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database Syst Rev. 11:CD004063. https://doi.org/10.1002/14651858.cd004063.pub4 Google Scholar
- Jung M, Ryu MH, Oh DY, Kang M, Zang DY, Hwang IG et al (2018) Efficacy and tolerability of ramucirumab monotherapy or in combination with paclitaxel in gastric cancer patients from the Expanded Access Program Cohort by the Korean Cancer Study Group (KCSG). Gastric Cancer 21(5):819–830. https://doi.org/10.1007/s10120-018-0806-1 (Epub 2018 Feb 9)CrossRefGoogle Scholar
- Kubo H, Komatsu S, Ichikawa D, Kawaguchi T, Kosuga T, Okamoto K et al (2016) Impact of body weight loss on recurrence after curative gastrectomy for gastric cancer. Anticancer Res 36(2):807–813Google Scholar
- Matsumoto H, Kawazoe A, Shimada K, Fukuoka S, Kuboki Y, Bando H et al (2018) A retrospective study of the safety and efficacy of paclitaxel plus ramucirumab in patients with advanced or recurrent gastric cancer with ascites. BMC Cancer. 18(1):120. https://doi.org/10.1186/s12885-018-4057-7 CrossRefPubMedCentralGoogle Scholar
- Moriwaki Y, Kunisaki C, Kobayashi S, Harada H, Imai S, Kasaoka C (2003) Does body mass index (BMI) influence morbidity and long-term survival in gastric cancer patients after gastrectomy? Hepatogastroenterology. 50(49):284–288Google Scholar
- Murahashi S, Takahari D, Wakatsuki T, Fukuda N, Ichimura T, Ogura M et al (2018) A retrospective analysis of ramucirumab monotherapy in previously treated Japanese patients with advanced or metastatic gastric adenocarcinoma. Int J Clin Oncol. 23(1):92–97. https://doi.org/10.1007/s10147-017-1192-0 (Epub 2017 Sep 14)CrossRefGoogle Scholar
- Park YS, Park DJ, Lee Y, Park KB, Min SH, Ahn SH et al (2018) Prognostic roles of perioperative body mass index and weight loss in the long-term survival of gastric cancer patients. Cancer Epidemiol Biomark Prev 27(8):955–962. https://doi.org/10.1158/1055-9965.EPI-18-0122 (Epub 2018 May 21)CrossRefGoogle Scholar
- Paulson AS, Hess LM, Liepa AM, Cui ZL, Aguilar KM, Clark J et al (2018) Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices. Gastric Cancer 21(5):831–844. https://doi.org/10.1007/s10120-018-0796-z (Epub 2018 Feb 3)CrossRefGoogle Scholar
- Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S et al (2015) Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US gastric cancer consortium. J Clin Oncol 33(33):3874–3879CrossRefGoogle Scholar
- Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y et al (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15:1224–1235CrossRefGoogle Scholar
- Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29(13):1715–1721. https://doi.org/10.1200/JCO.2010.33.0597 (Epub 2011 Mar 28)CrossRefGoogle Scholar