The phase III APACT trial evaluating adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs. gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC) previously failed to meet its primary endpoint of independently assessed disease-free survival. Nonetheless, the trial did indicate a benefit in overall survival in favour of adjuvant nap-P + Gem. Five year updated overall survival data are in line with this finding and continue to demonstrate an improved survival for patients in the nab-P + Gem arm.
Pancreatic cancer (PC) typically has a poor prognosis. Even with successful resection, the 5-year post-surgical survival rate is approximately 20%. Hoping to improve survival outcomes, the phase III APACT trial investigated the efficacy and safety of adjuvant nab-paclitaxel (nab-P) and gemcitabine (Gem) compared to Gem alone in patients with resected PC. Unfortunately, the study failed to meets the primary endpoint of independently assessed disease-free survival (DFS) (19.4 months vs. 18.8 months; HR[95%CI]: 0.88[0.729-1.063], p= 0.1824). However, the prespecified sensitivity analysis for median investigator-assessed DFS favoured nab-P plus Gem (p= 0.0168). Furthermore, both at the time of the primary analysis (p= 0.045) and at a post-hoc updated follow-up analysis (p= 0.023), the median overall survival (OS) was longer for patients treated with nab-P + Gem. At the 2021 ESMO World Congress on Gastrointestinal Cancer, updated five-year OS results in the intent-to-treat (ITT) population were presented.
APACT study design
APACT is a phase III, international multicentre, open-label trial (1:1) including 866 treatment-naïve patients with pancreatic ductal adenocarcinoma (T1-3, N0/N1, M0) who had received a macroscopic complete resection (R0, R1). Eligible patients were required to have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, a CA19-9 concentration <100 U/mL and no radiological evidence of disease. Patients were randomised as early as possible after adequate recovery from surgery (no later than twelve weeks after surgery) to either nab-P (125 mg/m2) plus Gem (1,000 mg/m2) or Gem only (1,000 mg/m2) on days 1, 8 and 15 of six 28-day cycles. The primary endpoint was DFS by independent review, with secondary study objectives including OS and safety.
Reduction in the risk of death by 20%
Baseline characteristics were well balanced between the two study arms. The median age in both arms was 64 years, approximately three quarters of patients had a R0 resection, 72% had a positive nodal status and 60% had an ECOG PS of 0 at study initiation. Most patients in the trial had a T3 tumour stage (87%). At a median follow-up of 63.2 months for OS, 268 and 287 events had occurred in the ITT population with nab-P plus Gem and Gem alone (88% mature), respectively. The corresponding median OS was 41.8 and 37.7 months (HR[95%CI]: 0.80[0.678-0.947], p= 0.0091), with 5-year OS rates of 38% and 31%, respectively. With this, five-year OS outcomes were consistent with those observed in both the primary analysis and the prior post-hoc updated analysis. Patterns of OS were generally consistent across all prespecified subgroups, including R0 (HR[95%CI]: 0.85[0.698-1.034]) and R1 patients (HR[95%CI]: 0.73[0.534-1.003]), as well as lymph node positive (HR[95%CI]: 0.77[0.636-0.922]) and negative (HR[95%CI]: 0.97[0.667-1.415]) patients. Of note, the survival benefit from nab-P plus Gem seemed to be smallest in patients with a poorly differentiated tumour grade (HR[95%CI]: 1.04[0.746-1.442]).
Five-year OS outcomes of the APACT study were consistent with OS data from the primary analysis and prior post-hoc updated analysis for nab-P + Gem and Gem alone. Although APACT failed to meet its primary endpoint of independently assessed DFS in the primary analysis, these OS data do suggest an improved survival for patients with resected pancreatic cancer who received nab-P plus Gem.
Tempero M, et al. Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC): Updated 5-year overall survival. Presented at 2021 ESMO World Congress on Gastrointestinal Cancer; Abstract LBA-1.