Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)

• Published in: Annals of oncology Vol. 24; no. 11; pp. 2875 - 2880
• Main Authors: Chang, A., Manegold, C., Douillard, J.-Y., Malik, R., Giaccone, G., Begbie, S., Jennens, R., Tzekova, V., Couture, F., Hirsh, V., Burkes, R., Sangha, R., Ambrus, M., Janaskova, T., Musil, J., Jakesova, J., Roubec, J., Vanasek, J., Barlesi, F., Bennouna-Louridi, J., Chouaid, C., Robinet, G., Souquet, P.-J., Spaeth, D., Schott, R., Lena, H., Baize, N., Molinier, O., Fuchs, F., Marschner, N., Schuette, W., Syrigos, K., Papandreou, C., Bocskei, C., Juhasz, E., Losonczy, G., Mark, Z., Molnar, I., Papai-Szekely, Z., Tehenes, S., Vinkler, I., Maru, A., Pathak, A., Prasad, S.V.S.S., Kilara, N., Gorijavolu, D., John, S., Amoroso, D., Bajetta, E., Bonetti, A., Maio, M., Passalacqua, R., Bitina, M., Brize, A., Purkalne, G., Skrodele, M., Samson-Fernando, M.C., Jassem, J., Koralewski, P., Cebotaru, C., Ganea-Motan, D.E., Ianuli, C.H., Manolescu, I.G., Udrea, A., Burdaeva, O., Filippov, A., Lazarev, S., Tan, Y.O., Bastus Piulats, R., Garcia-Foncillas, J., Valdivia, J., de Castro, J., Lee, J.-S., Lee, J.S., Shin, S.W., Kim, Y.-C., Chang, G.-C., Goan, Y.-G., Kuo, H.-P., Demir, G., Crawford, J., Agarwal, M., Pandit, S., Araujo, R., Vrindavanam, N., Bonomi, P., Wade, J., Camidge, R., Hill, D., Rarick, M., Flynn, P., Savin, M., Richards, D., Dangoor, A., Summers, Y., Rankin, E., Rowley, K., Kristeleit, H., Taylor, P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2013; Oxford University Press
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunotherapy; Kaplan-Meier Estimate; Lactoferrin - administration & dosage; Lactoferrin - adverse effects; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; non-small-cell lung cancer; Pharmacology. Drug treatments; phase III study; Placebos; Pneumology; talactoferrin; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; talactoferrin; immunotherapy; phase III study; non-small-cell lung cancer; Phase III trial; Human; Lung disease; Treatment resistance; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Treatment; Immunotherapy; Placebo; Bronchus disease; Clinical trial; Advanced stage; Talactoferrin alfa; Comparative study; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdt371

Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.