May 2022: Effect of denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy for primary breast cancer – results from GeparX trial

The GeparX (NCT02682693) was a multicenter, prospective, open-label, phase 2b, 2 × 2 randomized clinical trial conducted by GBG and AGO-B at 38 German sites between February 2017 and March 2019. Eligible patients had unilateral or bilateral primary breast cancer, stage cT2-cT4a-d or cT1c, with either clinically node-positive or pathologically node-positive or HR-negative disease, or Ki-67 proliferation index greater than 20%, or HER2-positive breast cancer. Primary objective was to determine whether adding denosumab to anthracycline/taxane-containing neoadjuvant chemotherapy increases the pathological complete response (pCR) rate and which nab-paclitaxel schedule is more effective in this neoadjuvant setting.

Highlights:

• Denosumab added to anthracycline/taxane-based neoadjuvant chemotherapy does not improve pCR rates.
• Nab-paclitaxel weekly significantly (α=0.10) increases pCR rates compared to d1,8 q3w, especially in TNBC.
• High-grade toxicity did not differ with or without denosumab.
• The rate of high-grade nonhematologic adverse events was significantly higher with nab-paclitaxel weekly compared to d1,8 q3w (33.7% vs 24.1%; p=0.004).

Conclusion: In the GeparX trial, denosumab added to anthracycline/taxane-based neoadjuvant chemotherapy did not improve pCR rates. Nab-paclitaxel at a dosage of 125 mg/m2 weekly significantly increased the pCR rate compared with the days 1 and 8, every-3-weeks schedule overall and in TNBC, but generated higher toxicity.

Blohmer JU, Link T, Reinisch M, et al. Effect of Denosumab Added to 2 Different nab-Paclitaxel Regimens as Neoadjuvant Therapy in Patients With Primary Breast Cancer: The GeparX 2 × 2 Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1010-1018. doi: 10.1001/jamaoncol.2022.1059.

• PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35588050/