In the “real world” NABUCCO trial, results with nab-paclitaxel were consistent with those reported in the pivotal trial among patients with metastatic breast cancer who are ineligible to receive anthracycline therapy.
Karin Potthoff, MD
Karin Potthoff, MD
In the “real world” NABUCCO trial, results with nab-paclitaxel were consistent with those reported in the pivotal trial among patients with metastatic breast cancer who are ineligible to receive anthracycline therapy.1The benefits associated with the treatment extend also to patients who are 65 years or older, said Karin Potthoff, MD, of IOMEDICO AG in Freiburg, Germany, during a poster session at the 2016 ESMO Congress.
In a pivotal phase III trial by Gradishar et al,2nab-paclitaxel was compared with paclitaxel in a similar patient population. Results showed that the overall response rate (ORR) with nab-paclitaxel was 33%. The time to tumor progression was 23.0 weeks with nab-paclitaxel and 16.9 weeks with paclitaxel, and an overall survival (OS) of 60 weeks.
Nab-paclitaxel was associated with an acceptable toxicity profile in this trial. Grade 3 peripheral sensory polyneuropathy occurred in 10% of patients and was the most critical safety issue.
While several clinical trials of nab-paclitaxel have been conducted, prospective data on real-world practice consistent with increased use of prior taxane-containing regimens in the neoadjuvant setting were lacking, explained Potthoff in an interview withTargeted Oncology. “We wondered if patients, in fact, were able to receive the recommended 260 mg/m2dose or if it was too toxic,” she added.
Therefore, in the real-world German NABUCCO study,2investigators collected data on routine treatment from 2012 to 2015 of 697 patients with metastatic breast cancer and contraindications for anthracycline therapy in approximately 100 oncology outpatient centers across Germany. Data on treatment for a maximum of 6 months were captured, with follow-up for a median of 17.7 months including details on disease progression, OS, and safety with focus on neurotoxicity.
A total of 419 patients (60.1%) received prior taxane therapy. The median age in the overall trial was 62.3 years, with 58.2% being less than 65 years of age. Median time from primary diagnosis was 65.2 months.
Dosing schedules, which were at the discretion of the physician, ranged from 78 to 260 mg/m2and with cycles from q3w to q4w. Nab-paclitaxel was administered as a first-, second-, third- and fourth- or later-line therapy in 40%, 24%, 20%, and 15% of patients, respectively.
Receptor status varied in the NABUCCO population: hormone receptor (HR)-positive/HER2-negative (58.4%), HR-positive/HER2-positive (9.9%), HR-negative/HER2-positive (3.9%), triple-negative breast cancer (TNBC; 13.8%) and unknown (14.1%).
The ORR across the study population was 37.2%. In the first-line setting, nab-paclitaxel was associated with a 46.1% ORR; in second-line, the ORR was 32%. Third-line paclitaxel was associated with a 31.9% ORR, while treatment in fourth-line and beyond led to a 29.0% ORR.
Stable disease percentages ranged from 30.5% in third-line therapy to 37.3% in second-line therapy. Response rates were highest among patients who were HR-negative/HER2-positive (55.6%) and lowest in TNBC (32.7%).
“That rate for triple-negative disease is still quite good,” Potthoff commented. Progressive disease was highest in TNBC (27.1%) and lowest in HR-negative/HER2-positive (11.1%).
Although responses were lower in patients 65 years and older than those were younger (31.6% vs 41.1%), progressive disease was not higher in older patients (17.2% vs 20.0%). Also, ORRs were not reduced in patients who received doses lower than 260 mg/m2.
The median time to tumor progression was 5.9 months for the overall population and similar for those less than 65 years (5.7 months) and 65 years or older (6.5 months). It was shortest for those with TNBC (4.9 months) and longest for patients who were HR-positive/HER2-positive (8.6 months).
Grade 3/4 neurotoxic adverse events (AEs) were observed in 5.2% of patients, particularly peripheral sensory neuropathy (4.3%), peripheral motor neuropathy (1.1%) and paresthesia (0.1%).
Grade 1/2 AEs were reported in 47.3% of patients, peripheral sensory neuropathy being the most common (35.0%). Rates for peripheral motor neuropathy and paresthesia were 11.6% and 8.6%, respectively.
Potthoff said that despite the common phenomenon of underreporting in non-interventional studies, the explicit focus on capturing neurotoxic adverse events during NABUCCO resulted in an overrepresentation of neurotoxic events compared with other adverse events.
Additionally, she underscored that response rates were high in populations typically difficult to treat: patients who had received multiple lines of prior therapy, in elderly patients, and those with TNBC.
“Our real-world data from NABUCCO confirm the earlier clinical trial findings,” Potthoff concluded. “They confirm also that nab-paclitaxel is an effective and safe treatment option with a favorable benefit-risk profile in metastatic breast cancer patients not eligible for anthracycline therapy.”