As reported in the Journal of Clinical Oncology by Margaret A. Tempero, MD, and colleagues, the phase III APACT trial has shown no improvement in independently assessed disease-free survival (the study’s primary endpoint) with the addition of adjuvant nab-paclitaxel to gemcitabine in treatment-naive patients with pancreatic ductal adenocarcinoma. However, an overall survival benefit was observed.
Margaret A. Tempero, MD
Study Details
The open-label trial included 866 patients with resected pancreatic ductal adenocarcinoma from sites in 21 countries. They were randomly assigned between April 2014 and April 2016 to receive nab-paclitaxel at 125 mg/m2 followed by gemcitabine at 1,000 mg/m2 (nab-paclitaxel group, n = 432) or gemcitabine at 1,000 mg/m2 alone (control group, n = 434) in single intravenous infusions on days 1, 8, and 15 of 28-day cycles, for up to six cycles. The primary endpoint was disease-free survival on independent review; overall survival was a secondary endpoint.
Disease-Free and Overall Survival
At data cutoff for the primary analysis (end of December 2018), median follow-up was 38.5 months (interquartile range [IQR] = 33.8–43 months). Median disease-free survival on independent assessment was 19.4 months (95% confidence interval [CI] = 16.6–21.9 months) in the nab-paclitaxel group vs 18.8 months (95% CI = 13.8–20.3 months) in the control group (hazard ratio [HR] = 0.88, 95% CI = 0.73–1.06, P = .18).
In a prespecified sensitivity analysis, investigator-assessed median disease-free survival was 16.6 months (IQR = 8.4–47.0 months) in the nab-paclitaxel group vs 13.7 months (IQR = 8.3–44.1 months) in the control group (HR = 0.82, 95% CI = 0.69–0.96, P = .02).
Overall, 55% of patients in the nab-paclitaxel group vs 56% of those in the control group received a subsequent new anticancer therapy or cancer-related surgery, with the most common treatment being fluorouracil-based regimens (47% and 42%); a new nab-paclitaxel-based therapy was received by 8% vs 21%.
KEY POINTS
- The addition of nab-paclitaxel to gemcitabine did not significantly improve independently assessed disease-free survival.
- The combination was associated with an overall survival benefit.
At the time of primary analysis (68% data maturity), median overall survival was 40.5 months (IQR = 20.7 months to not reached) in the nab-paclitaxel group vs 36.2 months (IQR = 17.7–53.3 months) in the control group (HR = 0.82, 95% CI = 0.68–0.996, P = .045). At 16-month follow-up (data cutoff in April 2020; 81% data maturity) with a median follow-up of 51.4 months (IQR = 47.0-57.0 months), median overall survival was 41.8 months (95% CI = 35.5–47.3 months) vs 37.7 months (95% CI = 31.1–40.5 months; HR = 0.82, 95% CI = 0.69–0.97, P = .023). At 5-year follow-up (data cutoff in April 2021, 88% data maturity) with a median follow-up of 63.2 months (IQR = 60.1–68.7 months), median overall survival was 41.8 vs 37.7 months (HR = 0.80, 95% CI = 0.68–0.95, P = .009).
Adverse Events
Grade ≥ 3 adverse events occurred in 86% of patients in the nab-paclitaxel group vs 68% of those in the control group. The most common adverse events in the nab-paclitaxel group were neutropenia (49% vs 43% in the control group), anemia (15% vs 8%), peripheral neuropathy (15% vs 0%), and fatigue (10% vs 3%). Serious adverse events occurred in 41% vs 23% of patients. Adverse events led to discontinuation of nab-paclitaxel in 27% and gemcitabine in 17% of patients in the nab-paclitaxel group, and to discontinuation of gemcitabine in 10% of patients in the control group. Adverse events led to death in two patients in the nab-paclitaxel group (due to pneumonia and sepsis) and two patients in the control group (due to liver injury/hepatic failure and capillary leak syndrome).
The investigators concluded, “The primary endpoint (independently assessed disease-free survival) was not met, despite favorable overall survival seen with nab-paclitaxel plus gemcitabine.”
Dr. Tempero, of the UCSF Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and by Celgene, a Bristol Myers Squibb Company. For full disclosures of the study authors, visit ascopubs.org.
