Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

Laura Testa, Max Mano, Roberto Jun Arai, Renata Colombo Bonadio, Sergio V Serrano, Marina M Costa Zorzetto, Susanne Crocamo, Oren Smaletz, Ruffo Freitas-Junior, Paulo M Hoff, Laura Testa, Max Mano, Roberto Jun Arai, Renata Colombo Bonadio, Sergio V Serrano, Marina M Costa Zorzetto, Susanne Crocamo, Oren Smaletz, Ruffo Freitas-Junior, Paulo M Hoff

Abstract

Objectives: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET).

Methods: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239.

Results: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively.

Conclusions: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.

Conflict of interest statement

RCB received financial support for educational programs from AstraZeneca and for attending symposia from Roche and AstraZeneca, and personal fees for expert testimony from Aché. All other authors have no conflicts of interest to disclose.

Figures

Figure 1. CONSORT diagram. RECIST, Response Evaluation…
Figure 1. CONSORT diagram. RECIST, Response Evaluation Criteria in Solid Tumors.
Figure 2. Lewis Y antigen expression of…
Figure 2. Lewis Y antigen expression of the patient with stable disease for more than 2 years who was administered hu3S193 according to immunohistochemistry. A. Predominant membrane Lewis Y staining ×200. B. Membrane and cytoplasm Lewis Y staining ×200.
Figure 3. Kaplan-Meier curves of (A) time…
Figure 3. Kaplan-Meier curves of (A) time to progression and (B) overall survival for patients with advanced hormone-receptor positive breast cancer who were administered anti-Lewis Y monoclonal antibody (hu3S193) (intention-to-treat population).

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