P5-18-03: First Interim Toxicity Analysis of the Randomized Phase III WSG Plan B Trial Comparing 4xEC-4xDoc Versus 6xTC in Breast Cancer Patients with HER2 Negative Breast Cancer (BC).
Authors: U Nitz, O Gluz, H Krepe, B Liedtke, B Aktas, S Henschen, A Pollmanns, P Krabisch, I Zuna, S Shak, C Thomsseen, N Harbeck
Journal: Cancer Research (2011)

Abstract Background: Anthracycline-taxane based adjuvant chemotherapy (cht) is considered standard in node-positive and high-risk node-negative BC. However, retrospective analyses suggest that in HER2−BC, benefit from anthracyclines may not outweigh acute and long term toxicities. Recurrence Score (RS) identifies patients who are not candidates for cht based on their low relapse risk, as well as minimal, if any, benefit of cht. The WSG Plan B trial investigates anthracycline-free cht in HER2− BC and is the first trial in Europe prospectively incorporating RS for decision making regarding adjuvant cht in both N0 and N+ BC. Methods: Plan B trial randomizes HER2− BC patients with high-risk N0 (at least one risk factor: ≥pT2; negative HR status; G2-3; age ≤35 years old; high uPA/PAI-1) or N+ disease to 6xTC (Docetaxel 75Cyclophosphomide600) vs. 4xEC (Epirubicin90Cyclophosphomide600)-4xDocetaxel100 G-CSF prophylaxis is recommended according to current ASCO guidelines. The statistical design previews n=2.448 randomized to cht; patients with HR+ BC, N0-3 and a RS ≤11 receive endocrine therapy only. Results: From April 2009 to June 2011, 3037 patients have been recruited and 2296 randomized (TC/EC-Doc: 1146/1150; age &amp;lt;65 years old: 900/911; ≥65 years old: 246/239). From the patients with HR+ disease (n=2368) 18% had a RS 0–11, 61% a RS 12–25 and 21% a RS ≥ 25. In patients with 0–3 positive LN and RS of 0–11 (n=329) who opted for no cht 257 are in the observational arm. In the group with an intermediate risk (RS 12–25) 14% drop outs before start of cht have been reported. In 1172 fully monitored patients 22 toxicity-related therapy stops have been reported in the TC and 34 in the EC-Doc arm (p=0.12). 614 serious adverse events (SAE) have been reported (299 TC vs. 315 EC-Doc). There is no difference in patients &amp;lt;65 years old (TC vs. EC-Doc: 218/218), but slightly more SAE's in patients ≥65 years old treated by EC-Doc (97 vs. 81, p=0.13). The most frequent SAEs were: leucopenia, febrile neutropenia (TC/EC-Doc:37 (3.3%)/31 (2.7%), n.s.), infections and heart/vascular events (TC/EC-Doc 29/40, n.s.). In patients ≥65 years old, there is a trend towards more febrile neutropenia (13 vs. 5; p=0.06) in the TC, and more severe mucositis/diarrhea/nausea (3 vs. 15; p=0.007) and heart/vascular events (5 vs. 14; p=0.06) in the EC-Doc arm. There were 5 therapy related deaths (TC 5 (0.4%)/EC-Doc 0, p=0.03); 3 in patients &amp;lt;65 years, 2 in patients ≥65 years (4 due to sepsis, 1 due to cardiac failure). Detailed data on relationship between the protocol specified, RS-guided treatment assignment and toxicity, and use of G-CSF support will be updated for the meeting. Conclusions: The Plan-B trial is one of the largest randomized phase III trials currently evaluating anthracycline-free adjuvant cht in HER2− BC. The cht administered within the study was generally well tolerated, but higher number of treatment-related deaths has been observed within the TC arm. The short term toxicity profile seems be different between both study arms, particularly in patients &amp;gt;65 years old. On the basis of prognosis as determined by RS, cht has been spared after a shared decision process in a substantial group of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-03.