medwireNews: Adding denosumab to neoadjuvant chemotherapy does not improve pathologic complete response (pCR) rates in people with breast cancer, show data from the GeparX trial.
The study, which had a 2 x 2 randomized design, also revealed that weekly nab-paclitaxel was associated with a significantly higher pCR than a 3-weekly schedule, but at the cost of increased toxicity.
In total, 779 women and one man with breast cancer were randomly assigned to receive denosumab 120 mg every 4 weeks for six cycles or no denosumab in combination with either nab-paclitaxel 125 mg/m2 per week for 12 weeks or the same dose given on days 1 and 8 of a 3-week cycle for four cycles (eight doses). All patients were then given four cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 or 3 weeks, according to the physician’s choice.
In addition, participants with HER2-positive disease (n=153) were given the trastuzumab biosimilar ABP980 6 mg/kg plus pertuzumab 420 mg every 3 weeks for eight cycles, while those with triple-negative breast cancer (n=317) received weekly carboplatin AUC 2 for 12 weeks at the same time as the nab-paclitaxel regimens.
Sibylle Loibl (German Breast Group, Neu-Isenburg) and co-investigators report that, following surgery, the pCR rate was 41.0% among the participants who received denosumab and 42.8% among those who did not, a nonsignificant difference. There were also no significant differences when the data were stratified by breast cancer subtype, the epirubicin/cyclophosphamide schedule, or lymphocyte predominance.
However, using a significance level of α=0.10, the researchers found that people who were given nab-paclitaxel weekly had a significantly higher pCR rate than those who received it on days 1 and 8 every 3 weeks, at 44.9% versus 39.0%.
Additionally, weekly nab-paclitaxel was associated with a significantly higher pCR than the 3-weekly schedule among people with triple-negative breast cancer (60.4 vs 50.0%), those who received epirubicin/cyclophosphamide every 2 weeks (46.9 vs 36.7%), and those who received denosumab (48.2 vs 33.8%) but not in other subgroups.
The researchers note in JAMA Oncology that denosumab use did not affect chemotherapy discontinuation rates, delays, or dose reductions but weekly nab-paclitaxel was associated with significantly higher rates of all three relative to the 3-weekly regimen.
There were also no significant differences in adverse event (AE) rates between the two denosumab arms, whereas grade 3 or 4 nonhematologic AEs were significantly more common with nab-paclitaxel weekly compared with the 3-weekly schedule, at 33.7% versus 24.1%.
Finally, the team looked at patient-reported quality of life (QoL). They observed no significant QoL differences between the two denosumab arms but found that patients receiving nab-paclitaxel weekly reported significantly worse mean scores for physical and functional well-being, additional concerns, and FACT-Taxane total score than those receiving nab-paclitaxel on days 1 and 8 every 3 weeks.
Loibl et al conclude: “Overall, results are suitable for guiding research; however, nab-paclitaxel is approved only for the treatment of metastatic [breast cancer] and, despite reassuring data, cannot currently be considered as a standard neoadjuvant treatment of [breast cancer].”
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