Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial
- 96 Downloads
The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2.
In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model.
Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0–1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09–2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41–4.84, p = 0.005) were the only significant poor prognostic factors for OS.
Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.
KeywordsGastric neoplasm Survival Prognosis Second-line chemotherapy
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to declare.
All participants gave their written informed consent before inclusion in the FFCD-0307 trial. The study was approved by relevant ethics committees.
- 2.Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7. https://doi.org/10.1200/JCO.2006.06.8429.CrossRefPubMedGoogle Scholar
- 5.Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefGoogle Scholar
- 6.Ford HER, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15:78–86. https://doi.org/10.1016/S1470-2045(13)70549-7.CrossRefPubMedGoogle Scholar
- 7.Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, et al. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer 1990. 2014;50:1437–45. https://doi.org/10.1016/j.ejca.2014.01.020.CrossRefGoogle Scholar
- 8.Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer—a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011;47:2306–14. https://doi.org/10.1016/j.ejca.2011.06.002.CrossRefPubMedGoogle Scholar
- 9.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9. https://doi.org/10.1016/S0140-6736(13)61719-5.CrossRefPubMedGoogle Scholar
- 10.Wilke H, Muro K, Van Cutsem E, Oh S-C, Bodoky G, Shimada Y, et al. 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. 2014;15:1224–35. https://doi.org/10.1016/S1470-2045(14)70420-6.CrossRefPubMedGoogle Scholar
- 11.Kang Y-K, Boku N, Satoh T, Ryu M-H, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71. https://doi.org/10.1016/S0140-6736(17)31827-5.CrossRefPubMedGoogle Scholar
- 12.Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014;32:3520–6. https://doi.org/10.1200/JCO.2013.54.1011.CrossRefPubMedGoogle Scholar
- 13.Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin. 2013;31:4438–44. https://doi.org/10.1200/JCO.2012.48.5805.CrossRefGoogle Scholar
- 15.Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer–pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol. 2004;22:2395–403. https://doi.org/10.1200/JCO.2004.08.154.CrossRefPubMedGoogle Scholar
- 17.Hashimoto K, Takashima A, Nagashima K, Okazaki S, Nakajima TE, Kato K, et al. Progression-free survival in first-line chemotherapy is a prognostic factor in second-line chemotherapy in patients with advanced gastric cancer. J Cancer Res Clin Oncol. 2010;136:1059–64. https://doi.org/10.1007/s00432-009-0752-8.CrossRefPubMedGoogle Scholar
- 21.Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642–53. https://doi.org/10.1016/S1470-2045(11)70102-4.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Carmona-Bayonas A, Jiménez-Fonseca P, Custodio A, Sánchez Cánovas M, Hernández R, Pericay C, et al. Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry. Gastric Cancer. 2017. https://doi.org/10.1007/s10120-017-0718-5.CrossRefPubMedGoogle Scholar