Randomized, Double-Blind, Placebo-Controlled Phase II Study of Single-Agent Oral Talactoferrin in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer That Progressed After Chemotherapy

Abstract

TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.

Targeting the immune system for management of NSCLC: the revival?

“…In a randomized phase II study, talactoferrin had activity against previously untreated stage IIIB or IV NSCLC in combination with paclitaxel and carboplatin, improving the response to chemotherapy alone (paclitaxel, carboplatin, and placebo) by 18 % for evaluable patients (29 to 47 %; p = 0.05) and by 15 % in the intent-to-treat population (27 to 42 %; p = 0.08) [86]. A separate randomized phase II study revealed that talactoferrin monotherapy statistically improved OS in the intent-to-treat population by 65 % (vs placebo) in NSCLC that had progressed after at least two previous systemic regimens, which supported phase III exploration of the agent in this setting [71]. In both of the randomized phase II trials, the incidence of AEs was lower in the talactoferrin arms than in the control arms [71,86].…”

“…A separate randomized phase II study revealed that talactoferrin monotherapy statistically improved OS in the intent-to-treat population by 65 % (vs placebo) in NSCLC that had progressed after at least two previous systemic regimens, which supported phase III exploration of the agent in this setting [71]. In both of the randomized phase II trials, the incidence of AEs was lower in the talactoferrin arms than in the control arms [71,86]. Despite a promising phase II experience, a recently completed randomized phase III study in advanced pretreated NSCLC reported no improvements in OS or PFS for talactoferrin over placebo, each in combination with best supportive care [87].…”

“…Talactoferrin, an orally active recombinant human lactoferrin that is being evaluated as an anticancer agent, interacts with gut epithelium and gut-associated lymphoid tissue, resulting in recruitment and maturation of immature dendritic cells. Although the actions of talactoferrin may occur at a location that is distant from primary NSCLC tumors, it is postulated (on the basis of preclinical data) that talactoferrin-induced maturation of dendritic cells in the presence of tumor antigens and immune effector cells may subsequently enhance immune priming with tumor antigens, thereby promoting tumor infiltration of CD8+ T cells and natural killer cells and resulting in immunemediated tumor cell death [70,71].…”

“…To this end, talactoferrin has been assessed in clinical trials after evidence of antitumor activity against squamous cell and adenocarcinoma of the lung in animal models [71,84,85]. In a randomized phase II study, talactoferrin had activity against previously untreated stage IIIB or IV NSCLC in combination with paclitaxel and carboplatin, improving the response to chemotherapy alone (paclitaxel, carboplatin, and placebo) by 18 % for evaluable patients (29 to 47 %; p = 0.05) and by 15 % in the intent-to-treat population (27 to 42 %; p = 0.08) [86].…”

Lactoferrin, all roads lead to Rome

“…Indeed several placebo-controlled human cohort studies and clinical trials have already been performed. While not all these trials have been successful, several of them have shown significant beneficial effects (Manzoni et al 2009;Paesano et al 2010;Parikh et al 2011;Guntupalli et al 2013;Manzoni et al 2014), underscoring the need for continued research activity in this area. Typically in all these clinical studies the protein is very well tolerated, and clearly this bodes well for its future therapeutic use.…”