Efficacy and safety of a short-course (12-week) de-escalated neoadjuvant regimen (weekly paclitaxel/trastuzumab/pertuzumab) in early HER2-positive breast cancer: Interim analysis of a prospective study.

Abstract

599 Background: Standard neoadjuvant regimens for HER2-positive early breast cancer (EBC), such as 6 cycles of TCHP, achieve high pathological complete response (pCR) rates but carry significant toxicity risks. De-escalation strategies aiming to reduce treatment intensity and duration without compromising efficacy are clinically relevant. We present the interim analysis of a prospective study evaluating a shortened (12-week), carboplatin-free and anthracycline-free regimen (THP). Methods: We enrolled patients (pts) with histologically confirmed HER2-positive (IHC 3+ or ISH+) EBC, clinical stages T0-1N1M0 or T2-3N0-1M0. Pts received a de-escalated regimen consisting of 12 weekly infusions of paclitaxel (80 mg/m²) combined with trastuzumab and pertuzumab administered every 3 weeks for 4 cycles (12 weeks total). The primary endpoint was pCR rate (ypT0/is ypN0). Secondary endpoints included safety and treatment adherence. This interim analysis reports data from the first 70 pts who completed surgery. Results: Median age was 50 years. The cohort included 69% stage IIA and 31% stage IIB pts; 57% were cN0. 60% had HR-positive and 40% had HR-negative disease. Treatment compliance was excellent: 100% of pts completed the full 12-week course. The overall pCR rate was 60.0% (42/70). Efficacy was strongly associated with hormonal status: the pCR rate reached 82.1% (23/28) in the HR-negative subgroup, compared to 45.2% (19/42) in the HR-positive subgroup. The safety profile was exceptionally favorable compared to historical TCHP data. Grade ≥3 neutropenia occurred in only 4% of pts. No cases of febrile neutropenia or symptomatic cardiotoxicity were observed. Grade ≥3 non-hematological toxicity (diarrhea/rash) was limited to 8%. Peripheral neuropathy was predominantly grade 1, with occasional grade 2 events; no grade ≥3 neuropathy occurred. Conclusions: The short-course (12-week) de-escalated THP regimen demonstrated high efficacy, particularly in HR-negative/HER2-positive pts (pCR 82.1%), comparable to longer, more toxic multi-agent regimens. With a 0% rate of febrile neutropenia and 100% completion rate, this regimen represents a promising "chemo-light" option for selected patients, potentially guiding future de-escalation strategies in personalized oncology. Baseline characteristics and clinical outcomes (N=70). Characteristic / Endpoint N (%) or Median (Range) Median Age, years 50 (29–75) Node-positive disease (cN+) 30 (43%) HR-negative / HER2-positive 28 (40%) Completed full 12-week NACT 70 (100%) Breast-conserving surgery 34 (49%) Pathological Complete Response (Total) 42 (60.0%) pCR in HR-negative subgroup 23/28 (82.1%) pCR in HR-positive subgroup 19/42 (45.2%) Grade 3-4 Neutropenia 3 (4%) Febrile Neutropenia 0 (0%)