GeparX Trial: Adding Denosumab to Nab-Paclitaxel Regimens in Breast Cancer

By: Hope Craig, MSPH
Posted: Wednesday, August 31, 2022

In the GeparX randomized controlled trial published in JAMA Oncology, researchers in Germany investigated whether adding the RANK ligand inhibitor denosumab to anthracycline/taxane-containing neoadjuvant chemotherapy could increase the pathologic complete response rate in patients with early-stage breast cancer. Sibylle Loibl, MD, of Bethanien Hospital and Goethe University, Frankfurt, and colleagues also examined which nab-paclitaxel schedule may be more effective in the neoadjuvant chemotherapy setting. Although the optimal schedule for neoadjuvant nab-paclitaxel remains unclear, the investigators reported that the addition of denosumab may improve disease-free survival in those with hormone receptor–positive primary breast cancer.

Patients with unilateral or bilateral primary breast cancer, including 780 women and 1 man, were randomly assigned to receive or not receive denosumab (120 mg every 4 weeks for six cycles) and either nab-paclitaxel at 125 mg/m² weekly for 12 weeks or on days 1 and 8 every 3 weeks for four cycles (eight doses), followed by four cycles of epirubicin/cyclophosphamide (90/600 mg/m² every 2 weeks or every 3 weeks). Patients with triple-negative breast cancer received carboplatin. Patients with ERBB2-positive breast cancer received the trastuzumab biosimilar ABP980 plus pertuzumab.

Denosumab added to neoadjuvant chemotherapy did not improve pathologic complete response rates (41% with denosumab vs. 43% without, P = .58). However, despite more toxicity, weekly nab-paclitaxel resulted in a significantly higher pathologic complete response rate than the less-frequent regimen of nab-paclitaxel (45% vs. 39%, P = .06). The weekly nab-paclitaxel dosage was particularly effective for patients with triple-negative breast cancer compared with the less-frequent regimen (60.4% vs. 50.0%, P = .06). More patients receiving weekly nab-paclitaxel discontinued treatment than those who received it less frequently (20.5% vs. 6.2%, P < .001).

Disclosure: Full authors’ disclosures are available at jamanetwork.com.

JAMA Oncology

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