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Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

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Abstract

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response (pCR), and secondary endpoints were complete response (CR) and overall objective response (OR). 181 patients were randomized. A pCR was observed in 17% (12/71) of patients treated with gefitinib and in 12% (9/73) of patients treated with placebo (4.57% difference, 95% CI −7.19 to 6.33; P = 0.44). CR was observed in 10% of patients in both the gefitinib (7/71) and the placebo group (7/73) (0.27% difference, 95% CI −9.6 to 10.2; P = 0.96). There was no significant difference in OR (5.96%; 95% CI −9.9 to 21.9; P = 0.45) between the two groups. Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment. More patients in the gefitinib group discontinued treatment because of AE.

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Acknowledgments

The study was sponsored by Astra Zeneca. We would like to thank the following centers for provision of study material: Sweden: Malmö Hospital and Lund University Hospital. Norway: Trondheim Hospital and Rikshospitalet-Radiumhospitalet Oslo. Denmark: Herlev Hospital, Aarhus University Hospital, Odense University Hospital, Vejle Hospital, Roskilde Hospital, Naestved Hospital and Ringsted Hospital. Contribution of Charlotte Levin Tykjaer Jörgensen is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Oncology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen O, Denmark

    Mogens Bernsdorf & Bent Ejlertsen

  2. Department of Surgery, Clinical Sciences, Lund University, Lund, Sweden

    Christian Ingvar

  3. AstraZeneca Sverige, Södertalje, Sweden

    Leif Jörgensen

  4. Department of Oncology, Herlev Hospital, Herlev, Denmark

    Malgorzata K. Tuxen

  5. Department of Oncology, Lillebaelt Hospital, Vejle, Denmark

    Erik H. Jakobsen

  6. Department of Oncology, Rikshospitalet-Radiumhospitalet—Medical Center, Oslo, Norway

    Anna Saetersdal

  7. Department of Oncology, Odense University Hospital, Odense, Denmark

    Marie Louise Kimper-Karl

  8. Department of Breast Surgery, Copenhagen University Hospital, Copenhagen, Denmark

    Niels Kroman

  9. Department of Pathology, Herlev Hospital, Herlev, Denmark

    Eva Balslev

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  1. Mogens Bernsdorf
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  2. Christian Ingvar
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  10. Bent Ejlertsen
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Correspondence to Mogens Bernsdorf.

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Bernsdorf, M., Ingvar, C., Jörgensen, L. et al. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial. Breast Cancer Res Treat 126, 463–470 (2011). https://doi.org/10.1007/s10549-011-1352-2

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  • DOI: https://doi.org/10.1007/s10549-011-1352-2

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