Skip to main content

Advertisement

SpringerLink
Log in

Surgical Outcome after Neoadjuvant Chemotherapy and Bevacizumab: Results from the GeparQuinto Study (GBG 44)

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown increased pathological complete response rates when added to neoadjuvant chemotherapy. In various cancer types, bevacizumab treatment was accompanied by an increased risk of bleedings and other surgical complications. We assessed associated surgical complications.

Methods

In the GeparQuinto trial, 1,948 patients were randomized to receive four cycles epirubicin/cyclophosphamide (EC, 90/600 mg/m2 q3w) followed by four cycles docetaxel (D, 100 mg/m2 q3w) each with (ECB-DB) or without (EC-D) bevacizumab (B, 15 mg/kg q3w) concurrent with chemotherapy. Surgery had to be performed not earlier than 28 days after the last bevacizumab infusion, but within days 21 and 35 after the last chemotherapy.

Results

In 743 (38.1 %) patients, a surgical complication (bleedings, hematomas, necrosis, wound infections, abscess) was documented prospectively. Baseline characteristics of the patients were well balanced between both arms. The breast-conserving surgery (BCS) rate (N = 502) was 69.1 % (EC-D) and 71.9 % (ECB-DB; p = 0.464). The first surgical procedure was performed at a median of 29 (EC-D) and 34 days (ECB-DB) after last chemotherapy with or without bevacizumab infusion (p < 0.001). Surgical complications were documented in 38 (10.9 %; EC-D) and 59 (15.0 %; ECB-DB) patients (p = 0.103). Surgical complications were significantly higher after ECD-DB only in patients treated with BCS (N = 53; p = 0.029) or in those requiring repeat surgery in order achieve clear margins (N = 23; p = 0.037) compared to the EC-D group.

Conclusions

Addition of bevacizumab to neoadjuvant chemotherapy might be associated with an increased risk for surgical complications in patients treated with BCS or after repeated surgeries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Chang HY, Nuyten DS, Sneddon JB, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005;102:3738–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.

    Article  Google Scholar 

  3. Gerber B, Loibl S, Eidtmann H, et al. Neoadjuvant bevacizumab and anthrcycline-taxane based chemotherapy in 678 triple negative primary breast cancers; results from the GEPARQUINTO study (GBG 44). Ann Oncol. 2013;24(12):2978–84. doi:10.1093/annonc/mdt361.

    Article  CAS  PubMed  Google Scholar 

  4. Makhoul I, Klimberg VS, Korourian S, et al. Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer. Am J Clin Oncol. 2013. doi:10.1097/COC.0b013e31828940c3.

  5. Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30:2039–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.

    Article  CAS  PubMed  Google Scholar 

  7. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–11.

    Article  PubMed  Google Scholar 

  8. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44.

    Article  CAS  PubMed  Google Scholar 

  9. Scappaticci FA, Fehrenbacher L, Cartwright T, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91:173–80.

    Article  CAS  PubMed  Google Scholar 

  10. Kabbinavar FF, Schulz J, McCleod M, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005;23:3697–705.

    Article  CAS  PubMed  Google Scholar 

  11. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.

    Article  CAS  PubMed  Google Scholar 

  12. Reck M, Barlesi F, Crinò L, et al. Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. Ann Oncol. 2012;23:1111–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009;27:1227–34.

    Article  CAS  PubMed  Google Scholar 

  14. Soria JC, Mauguen A, Reck M, et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013;24:20–30.

    Article  PubMed  Google Scholar 

  15. Smith IE, Pierga JY, Biganzoli L, et al. First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients. Ann Oncol. 2011;22:595–602.

    Article  CAS  PubMed  Google Scholar 

  16. Wedam SB, Low JA, Yang SX, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006;24:769–77.

    Article  CAS  PubMed  Google Scholar 

  17. Kriegel I, Cottu PH, Fourchotte V, et al. Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy. Anticancer Drugs. 2011;22:1020–3.

    Article  CAS  PubMed  Google Scholar 

  18. Cottu PH, Fourchotte V, Vincent-Salomon A, Kriegel I, Fromantin I. Necrosis in breast cancer patients with skin metastases receiving bevacizumab-based therapy. J Wound Care. 2011;20:403–4, 406, 408.

    Google Scholar 

  19. Lecarpentier E, Ouaffi L, Mir O, et al. Bevacizumab-induced small bowel perforation in a patient with breast cancer without intraabdominal metastases. Invest New Drugs. 2011;29:1500–3.

    Article  PubMed  Google Scholar 

  20. Lazzati V, Zygon J, Lohsiriwat V, Veronesi P, Petit JY. Impaired wound healing and bilateral mastectomy flap necrosis in a patient with locally advanced breast cancer after neoadjuvant Paclitaxel with bevacizumab. Aesthetic Plast Surg. 2010;34:796–7.

    Article  PubMed  Google Scholar 

  21. Kube R, Meyer F, Bien N, et al. Surgical management of bevacizumab-associated peritonitis due to perforation. Zentralbl Chir. 2009;134:462–7.

    Article  CAS  PubMed  Google Scholar 

  22. Kim HR, Jung KH, Im SA, et al. Multicentre phase II trial of bevacizumab combined with docetaxel-carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905). Ann Oncol. 2013;24:1485–90.

    Article  CAS  PubMed  Google Scholar 

  23. Li CY, Shan S, Huang Q, et al. Initial stages of tumor cell–induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst. 2000;92:143–7.

    Article  CAS  PubMed  Google Scholar 

  24. Huober J, Fasching PA, Hanusch C, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with non-responsive tumours to epirubicin/cyclophosphamide (EC) +/− bevacizumab—results of the randomised GeparQuinto study (GBG 44). Eur J Cancer. 2013;49:2284–93.

    Article  CAS  PubMed  Google Scholar 

  25. Bear HD, Tang G, Rastogi P, et al. The effect on surgical complications of bevacizumab added to neoadjuvant chemotherapy: NSABP protocol B-40. Cancer Res. 2011. doi:10.1158/0008-5472.SABCS11-PD07-08.

  26. Golshan M, Garber JE, Gelman R, et al. Does neoadjuvant bevacizumab increase surgical complications in breast surgery? Ann Surg Oncol. 2011;18:733–7.

    Article  CAS  PubMed  Google Scholar 

  27. Gordon CR, Rojavin Y, Patel M, et al. A review on bevacizumab and surgical wound healing: an important warning to all surgeons. Ann Plast Surg. 2009;62:707–9.

    Article  CAS  PubMed  Google Scholar 

  28. Erinjeri JP, Fong AJ, Kemeny NE, Brown KT, Getrajdman GI, Solomon SB. Timing of administration of bevacizumab chemotherapy affects wound healing after chest wall port placement. Cancer. 2011;117:1296–301.

    Article  CAS  PubMed  Google Scholar 

  29. Cortes J, Caralt M, Delaloge S, et al. Safety of bevacizumab in metastatic breast cancer patients undergoing surgery. Eur J Cancer. 2012;48:475–81.

    Article  CAS  PubMed  Google Scholar 

  30. NCI. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 5 Nov 2013.

Download references

Acknowledgment

We thank all patients and investigators for participation and Sanofi-Aventis and Roche, Germany, for financial support of this trial (NCT 00567554).

Disclosure

Gunter von Minckwitz has received honoraria and research found from Roche. Holger Eidtmann has received personal fees from Roche. Claus Hanusch has received personal fees from Novartis, Amgen, and Boeringer Ingelheim. Jens Blohmer has received honoraria from Roche. Jens Huober has received personal fees from Roche and Sanofi Aventis. Sibylle Loibl has received honoraria and research found from Roche. The other authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Rostock, Rostock, Germany

    Bernd Gerber MD

  2. Department Medicine and Research, German Breast Group, Neu-Isenburg, Germany

    Gunter von Minckwitz MD, Valentina Nekljudova PhD & Sibylle Loibl MD

  3. Department of Obstetrics and Gynaecology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Holger Eidtmann MD

  4. Department of Senology, Luisen-Hospital, Düsseldorf, Germany

    Mahdi Rezai MD

  5. Department of Obstetrics and Gynaecology, University of Erlangen, Erlangen, Germany

    Peter Fasching MD

  6. Department of Oncology, Bethanien-Hospital, Frankfurt, Germany

    Hans Tesch MD

  7. Department of Obstetrics and Gynaecology, University of Magdeburg, Magdeburg, Germany

    Holm Eggemann MD

  8. Gynaeco-oncological Practice, Hannover, Germany

    Iris Schrader MD

  9. Breast Center, Elisabeth Hospital, Kassel, Germany

    Kornelia Kittel MD

  10. Department of Senology, Rotkreuz-Klinikum, Munich, Germany

    Claus Hanusch MD

  11. Department of Obstetrics and Gynaecology, J.-W. Goethe-University, Frankfurt, Germany

    Gunter von Minckwitz MD & Christine Solbach MD

  12. Department of Obstetrics and Gynaecology, Hospital Offenbach, Offenbach, Germany

    Christian Jackisch MD

  13. St. Johannes Hospital, Dortmund, Germany

    Georg Kunz MD

  14. Department of Obstetrics and Gynaecology, Sankt Gertrauden Hospital, Berlin, Germany

    Jens-Uwe Blohmer MD

  15. Department of Obstetrics and Gynaecology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

    Jens Huober MD

  16. Department of Senology, Hospital, Rheinfelden, Germany

    Maik Hauschild MD

  17. Department of Obstetrics and Gynaecology, Helios Klinikum Berlin-Buch, Berlin, Germany

    Michael Untch MD

Authors
  1. Bernd Gerber MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gunter von Minckwitz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Holger Eidtmann MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahdi Rezai MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Fasching MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hans Tesch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Holm Eggemann MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Iris Schrader MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kornelia Kittel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Claus Hanusch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christine Solbach MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Christian Jackisch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Georg Kunz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jens-Uwe Blohmer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jens Huober MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Maik Hauschild MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Valentina Nekljudova PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Sibylle Loibl MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Michael Untch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gunter von Minckwitz MD.

Additional information

On behalf of the AGO B and the German Breast Group Investigators

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gerber, B., von Minckwitz, G., Eidtmann, H. et al. Surgical Outcome after Neoadjuvant Chemotherapy and Bevacizumab: Results from the GeparQuinto Study (GBG 44). Ann Surg Oncol 21, 2517–2524 (2014). https://doi.org/10.1245/s10434-014-3606-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-3606-9

Keywords

Search

Navigation