According to results from the phase 2 MARGOT/TBCR052 trial, there was not a statistically significant improvement of pathological complete response (pCR) rate with neoadjuvant paclitaxel plus margetuximab and pertuzumab when compared to paclitaxel plus trastuzumab and pertuzumab among patients with stage II to III HER2-positive breast cancer.

These results were first presented by Adrienne G Waks, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2024 San Antonio Breast Cancer Symposium.

The phase 2 MARGOT/TBCR052 trial enrolled 174 previously untreated patients with stage II to III HER2-positive early breast cancer, with 171 patients starting treatment. Patients were randomized on a 2-to-1 basis to receive either paclitaxel plus margetuximab and pertuzumab (margetuximab arm; n = 117) or paclitaxel plus trastuzumab and pertuzumab (trastuzumab arm, n = 54), for 4 cycles. The primary end point of this study was pCR, with additional end points including pCR rates by CD16A genotype, safety and tolerability of both neoadjuvant regimens.

The pCR rate of the margetuximab arm was 56% vs 46% in the trastuzumab arm, (95% confidence interval [CI], –8% to 27%; P = 0.25). Due to incomplete clinical response to the treatment regimens, 9% of patients in the margetuximab arm and 11% in the trastuzumab arm received additional neoadjuvant treatment, and were considered non-pCR at surgery. Among patients who were hormone receptor-positive (n = 111), the pCR rate was 54% in the margetuximab arm and 35% in the trastuzumab arm (P = .07). Among patients who were hormone receptor-negative (n = 59), the pCR rate was 60% in the margetuximab arm and 71% in the trastuzumab arm (P = .55). Among patients with an CD16A FF genotype, the pCR rate was 60% in the margetuximab arm and 50% in the pertuzumab arm (P = .36). Among patients with a CD16A FV genotype, the pCR rate was 52% in the margetuximab arm and 42% in the pertuzumab arm.

The incidence of patients with >1 grade ≥3 treatment-emergent adverse event was 27% in the margetuximab arm and 30% in the trastuzumab arm. The most common grade ≥2 treatment-emergent adverse events were infusion-related reaction, diarrhea, alopecia, and hypertension, with the only events more common in the margetuximab arm by > 10% being infusion-related reaction and alopecia. There was 1 death, in the margetuximab arm, with the cause unrelated to the study treatment.

Dr Waks concluded while “there was no statistically significant improvement in pCR rate” with paclitaxel, margetuximab, and pertuzumab, compared to paclitaxel/trastuzumab/pertuzumab for patients with stage II to III HER2-positive breast cancer and CD16A FF/FV genotype, a “numerical improvement in pCR rate with [paclitaxel, margetuximab, and pertuzumab] was seen and will be further investigated through comparison of circulating and tissue immune biomarkers across the 2 arms.”

Source:

Waks AG, Heiling H, Pohlmann P, et al. MARGOT/TBCRC052: A randomized phase II trial comparing neoadjuvant paclitaxel/margetuximab/pertuzumab (TMP) vs paclitaxel/trastuzumab/pertuzumab (THP) in patients (pts) with stage II-III HER2+ breast cancer. Presented at 2024 San Antonio Breast Cancer Conference. Dec 10-13, 2024; San Antonio, TX. Abstract LB1-02