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Trastuzumab plus GM-CSF for patients with trastuzumab-resistant, HER2-overexpressing metastatic breast cancer: Pilot study



Trastuzumab plus GM-CSF for patients with trastuzumab-resistant, HER2-overexpressing metastatic breast cancer: Pilot study



Journal of Clinical Oncology 23(16_suppl): 803-803



NlmCategory="UNASSIGNED">803 Background: Preclinical data suggest that the anti-tumor activity of trastuzumab (Herceptin) is partly due to antibody-dependent cellular cytotoxicity (ADCC) by immune effector cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF, Leukine) enhances ADCC by stimulating a variety of effector cells, including natural killer cells. In this pilot study, we tested the clinical antitumor effect of Herceptin plus GM-CSF in women with Herceptin-resistant metastatic breast cancer. Eligible patients (pts) had measurable, HER2-overexpressing, metastatic breast cancer; progressive disease (PD) after Herceptin ± chemotherapy; and good performance status (ECOG 0-1). Herceptin was given at 4 mg/kg IV followed by 2 mg/kg every wk for 4 wk (1 cycle). GM-CSF was given at 250 mcg/m2 SC daily until absolute neutrophil count (ANC) >10,000/mm3, then every other day while ANC was below 10,000/mm3. Treatment was continued until PD or intolerable toxicity. The primary endpoint was tumor response (including stable disease [SD]); disease was restaged every 8 wk. Thirteen women (median age 49 y, range, 27-71) with median 2.5 prior systemic treatments for metastatic disease (range 1-4), and 2 Herceptin failures (range 1-2) were entered with a median of 1 metastatic disease site (range 1-4); 3 pts had hormone-receptor-positive disease. Pts were given a median of 2 cycles Herceptin + GM-CSF (range 1-8). Ten pts were evaluable for response (1 did not complete the first cycle due to protocol violation and 1 was enrolled too recently for evaluation). Three pts (27.7%) had disease controlled: 2 have had SD for 4 months and 1 has had SD for 8 months. Three pts had transient reversible grade III toxicity (infection, dyspnea, headache) of uncertain relation to GM-CSF; 4 pts had grade I/II skin rash. In this pilot study, Herceptin + GM-CSF stabilized metastatic breast cancer previously treated and progressing on Herceptin. This approach warrants further investigation in a phase II study to determine if this response results from an increase in ADCC activity from GM-CSF. No significant financial relationships to disclose.

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Accession: 059163303

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PMID: 27945082



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