Geparquinto: An interim safety analysis of epirubicin/cyclophosphamide followed by docetaxel with or without bevacizumab as neoadjuvant chemotherapy for primary breast cancer patients
Authors: Von Minckwitz G. , Bauerfeind I. , Gerber B. , Eidtmann H. , Kaufmann M. , Costa S. D. , Loibl S. , Nekljudova V. , Untch M. 
Published: August 2020

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Background: The GeparQuinto trial is investigating the incorporation of bevacizumab (B), RAD001 (everolimus) for HER2-negative, and lapatinib for HER2-positive patients (pts) into neoadjuvant treatment regimens. As these targeted agents have not yet been adequately tested in combination with epirubicin (E), cyclophosphamide (C), and docetaxel (T) chemotherapy, a run-in phase of the trial was conducted for safety reasons. Methods: Starting in 11/2007, 62 pts received 4 cycles of E: 90 mg/m2 and C: 600 mg/m2, both on day 1 q day 21 followed by 4 cycles of T: 100 mg/m2, day 1 q day 21. Pts were randomized to receive this chemotherapy alone (EC-T, n=32) or concomitantly with B: 15 mg/kg i.v., day 1 q day 21 (ECB-TB, n=30). Main eligibility criteria for this part of the study were: histologically confirmed, HER2-negative, locally advanced breast cancer (cT3 cN+ and cT4), female, and ≥18 years of age with normal cardiac function (LVEF >55%). This interim toxicity analysis was a prerequisite for opening the main phase of the HER2-negative trial part to also include pts with cT2 tumors. Results: 61 pts received all cycles of EC (n=31 EC-T, n=30 ECB-TB), 1 pt discontinued on investigator's decision, 1 pt discontinued after EC due to disease progression. 18 pts received all cycles of T in each of the EC-T and ECB-TB groups. Reasons for discontinuation of T were adverse events (n=2 EC-T, n=1 ECB-TB) or investigator's decision (n=1 EC-T). 17 pts completed all cycles of B. Statistically significant differences in toxicities were only observed for grade 3–4 leucopenia during EC (40.6%) and ECB (70.0%; p=0.024) and for grade 1–4 [grade 3–4] mucositis during T (52.4% [9.5%]) and TB (100% [36.8%]; p<0.001 [p=0.060]). No statistically significantly different levels of other hematological or non-hematological toxicities were reported between the two arms. Conclusions: Addition of B to EC followed by T is feasible with the only increase in toxicity due to leucopenia and mucositis. Based on these data, the main phase of the trial was opened and has included over 450 pts to date.

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