Trastuzumab and interleukin-2 in HER2-positive metastatic breast cancer: A pilot study

Tanya Repka, Elena G. Chiorean, Juliette Gay, Katherine E. Herwig, Virginia K. Kohl, Douglas Yee, Jeffrey S Miller

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Purpose: Trastuzumab as a single agent has activity in metastatic breast cancer; however, the mechanism of action for this clinical activity is uncertain. Whereas interruption of erbB family member signaling occurs, trastuzumab also mediates antibody-dependent cellular cytotoxicity in vitro and in vivo. Based on these data, a clinical trial was performed to test whether interleukin (IL)-2, by increasing FcRγIII+ natural killer (NK) cell numbers and cytolytic function in vivo, when added to trastuzumab, can increase efficacy, be safely given, and avoid the use of chemotherapy. Experimental Design: In this Phase I trial, 10 patients with HER2-overexpressing metastatic breast cancer were treated with IL-2 (1.75 × 106 IU/m2/day, s.c.) for 7 weeks and trastuzumab (4 mg/kg load and then 2 mg/kg weekly) for 6 weeks. Safety, in vitro immune responses, and clinical responses were assessed. Results: Ten women received a total of 12 cycles of therapy (each cycle lasted 7 weeks). No significant toxicities were seen, and one patient required an IL-2 dose reduction. Among the evaluable patients (10 cycles), the responses were one partial response, five cases of stable disease, and four cases of progressive disease. In vitro immune assays showed NK cell expansion and trastuzumab-mediated increased NK cell killing of breast cancer targets (antibody-dependent cellular cytotoxicity) in a HER2-specific manner but did not correlate with clinical responses. Conclusions: Trastuzumab + IL-2 is a well-tolerated outpatient regimen that results in NK cell expansion with enhanced in vitro targeted killing of HER2-expressing cells. These preliminary data suggest that this strategy may benefit heavily pretreated metastatic breast cancer patients.

Original languageEnglish (US)
Pages (from-to)2440-2446
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number7
StatePublished - Jul 1 2003

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