Vliek, S.B., Van Werkhoven, E., Mandjes, I., Westphal, T., Lips, E.H., Mulder, L., Loo, C., Russel, N., Holtkamp, M., Schot, M., Baars, J., Karger, M., Honkoop, A.H., Bos, M E M M, Imholz, A.L.T., Vrijaldenhoven, S., Dezentje, V., Nederlof, P.M., and Linn, S.C.
Subgroup analyses of randomized, controlled trials (RCTs) using high dose chemotherapy (HD) with autologous stem cell support (autoSCT) reveal a potential benefit of HD in patients with triple negative breast cancer (TNBC) and in tumors harboring features of HRD (Vollebergh et al, 2011). The phase III part of the neo-TN RCT, compared neo-adjuvant HD with conventional treatment (CONV) in BRCA1-like TNBC. Patients with cT2-3N0-3M0 TNBC with HRD were randomized between HD or CONV after 3 courses of 2-weekly doxorubicin/cyclophosphamide (ddA 60 C 600). CONV treatment consisted of another 3xddAC, or in case of an unfavorable response on MRI a switch to 3 cycles capecitabine 800BID14-7 /docetaxel 75 ; after an amendment all patients switched to 3xcarboplatin AUC6 /paclitaxel 80weekly. The HD regimen consisted of a 4th course ddAC and 2 courses of cyclophosphamide 3000d1 /carboplatin 400d1,2 / thiotepa 250d2 both followed by autoSCT. Primary outcome was the Neo-adjuvant Response Index (NRI), secondary outcomes included overall (OS) and recurrence free survival (RFS). From 2010 to 2016, 122 patients were randomized (intention-to-treat). Median follow-up is 45 months. There was no significant difference in NRI between HD and CONV (mean NRI 0.78 versus 0.72, range 0-1, p = 0.41 Wilcoxon test). An NRI of > 0.7 was strongly associated with good prognosis (RFS of 97% [95%CI 93%-100%] versus 67% [95%CI 55%-82%] at 4 years). See Table for 4-years OS and RFS comparing HD with CONV. There were no treatment related deaths. However, 7 out of 55 patients who actually received HD did not complete HD mainly because of infections or allergic reactions. Table 187P Table HD % (95%CI) CONV % (95%CI) HR (95%CI) p-value All (n = 122) 4-yrs OS 4-yrs RFS 92 (85-99) 92 (85-99) 79 (69-91) 78 (68-89) 0.43 (0.15-1.23) 0.41 (0.15-1.07) 0.12 0.07 Stage III only (n = 35) 4-yrs OS 93 (81-100) 60 (39-93) 0.14 (0.02-1.14) 0.07 No significant efficacy differences were found between HD and CONV. The NRI is of prognostic value. Whether the HD regimen is promising, especially in very high risk BRCA1-like TNBC [HR = 0.14], requires additional data including a comparison with platinum treatment in all control arm patients. NCT01057069. The authors. The Dutch Cancer Foundation (KWF) and by the Schumacher Kramer Foundation. S.C. Linn: Research grant / Funding (self), research support for patients fees in D-Care study: Amgen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Research grant / Funding (self): Genentech; Advisory / Consultancy: IBM; Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (institution), patients fees in TEAM 2b study: Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Speaker Bureau / Expert testimony, Fee for teaching, paid to institution: Bayer. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]