Results from a recent clinical trial presented at the ESMO 21st World Congress on Gastrointestinal Cancer suggest that adjuvant nab-paclitaxel plus gemcitabine may be a viable treatment option for patients with pancreatic cancer ineligible to receive adjuvant FOLFIRINOX.

“Patients with pancreatic cancer have a poor prognosis. Even with resectable pancreatic cancer, the 5-year postsurgical survival rate is only approximately 20%,” explained Michele Reni, MD, IRCCS Ospedale, San Raffaele Scientific Institute, Milan, Italy, who presented the study results.

In metastatic pancreatic cancer, nab-paclitaxel plus gemcitabine demonstrated significantly longer overall survival (OS) than gemcitabine alone in a previous clinical trial (median OS, 8.7 months vs 6.6 months; P > .001).

The phase 3 APACT trial, presented in Barcelona, Spain was designed to assess the efficacy and safety of adjuvant nab-paclitaxel plus gemcitabine versus gemcitabine alone in the adjuvant setting.

Dr Reni noted that, since APACT was launched, gemcitabine plus capecitabine and mFOLFIRINOX became the preferred category 1 recommendations for adjuvant pancreatic cancer in the National Comprehensive Cancer Network guidelines.

The APACT trial included 866 treatment-naïve patients (median age, 64 years) with surgically resected pancreatic cancer and no evidence of metastases. Patients were randomized to receive nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 or gemcitabine 1000 mg/m2 alone. Therapy was administered for 6 cycles, with each cycle spanning 28 days, and initiated within 12 weeks of surgery. Patients were stratified by resection status, lymph node status, and geographic region.

The primary endpoint of the study was disease-free survival (DFS) based on central review performed by independent radiologists not associated with the trial. Dr Reni emphasized that this is the first time ever for this primary endpoint to be used in a clinical trial in this setting.

Secondary endpoints of the study included OS and safety data. EORTC QLQ-C30 and QLQ-PAN26 questionnaires were used to evaluate patients’ quality of life (QoL).

Approximately 70% of patients completed 6 therapy cycles (nab-paclitaxel plus gemcitabine, 66%, and gemcitabine, 71%), and follow-up lasted for median of 38.5 months.

The median independently-assessed DFS (n = 439 events) was 19.4 months for nab-paclitaxel plus gemcitabine versus 18.8 months for gemcitabine (hazard ratio [HR], 0.88; 95% CI, 0.729-1.063; stratified log-rank P = .1824). Notably, said Dr Reni, these results were in contrast with investigator-assessed DFS (n = 571 events), which was 16.6 months and 13.7 months for recipients of nab-paclitaxel plus gemcitabine and gemcitabine alone, respectively (HR 0.82; 95% CI, 0.694-0.965; nominal P = .0168).

The interim OS (n = 427 events) was 40.5 months with nab-paclitaxel plus gemcitabine versus 36.2 months with gemcitabine (HR, 0.82; 95% CI, 0.680-0.996; nominal P = .045). The data for this study is not yet fully mature, however (68%).

Dr Reni explained that safety data were as expected. Adverse events grade ≥3 were reported in 86% versus 68% of patients in the nab-paclitaxel plus gemcitabine and gemcitabine arms, respectively. The most common grade ≥3 hematologic and nonhematologic treatment-emergent adverse events were neutropenia (49% vs 43%, respectively) and fatigue (10% vs 3%).

Despite the mean EORTC QLQ-C30 global health status/QoL score being lower with nab-paclitaxel plus gemcitabine than with gemcitabine through 48 weeks (69.97 vs 72.59, respectively), mean scores were similar between the study arms during weeks 60 through 180. Similar trends were observed in other QLQ-C30 and QLQ-PAN26 subscales and Dr Reni noted that QoL scores generally improved throughout the study.

Ultimately, DFS was not found to be significantly improved per independent review, but the median DFS with gemcitabine alone was higher than in historical studies.

“Adjuvant nab-paclitaxel plus gemcitabine may be an option for those not eligible for adjuvant FOLFIRINOX,” Dr Reni concluded. “However, the impact of this regimen in the adjuvant setting may be clearer as survival data mature.”—Hina Khaliq.

Reference: Reni M, Riess H, O’Reilly E, et al. An international, randomized, open-label, phase III trial of adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for surgically resected pancreatic adenocarcinoma (APACT): primary analysis and quality of life outcomes.

This article is a news release from ESMO 21st World Congress on Gastrointestinal Cancer Meeting. Read the original here.