Is it important to adapt neoadjuvant chemotherapy to the visible clinical response? An open randomized phase II study comparing response-guided and standard treatments in HER2-negative operable breast cancer

Abstract

Background: Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment.

Methods: Overall, 264 previously untreated stage II-III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m(2), respectively, for 3 cycles) followed by docetaxel (100 mg/m(2) for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed.

Results: Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses.

Conclusion: Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.

Trial registration: ClinicalTrials.gov NCT00425516.

©AlphaMed Press; the data published online to support this summary is the property of the authors.

Figures

Figure 1.

Study design. The regimen adaptation was done at two levels after two and four cycles of treatment based on a percentage decrease of 30% and 50%, respectively, to define responders versus nonresponders Abbreviations: FEC100: fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 for three cycles.

Figure 2.

CONSORT diagram showing the flow of patients for treatment. Abbreviations: FEC: fluorouracil, epirubicin, and cyclophosphamide; RT, radiotherapy; SBR, Scarff-Bloom-Richardson.