Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer

Abstract

Background: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC.

Patients and methods: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses.

Results: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant.

Conclusion: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

Keywords: aged; albumin-bound paclitaxel; gemcitabine; geriatric assessment; pancreatic cancer; vulnerable population.

Figure 1.

CONSORT diagram of the study. The full analysis and efficacy analysis set comprised 233 and 197 patients, respectively. In the propensity score-matched analysis, 42 patients each from the gemcitabine plus nab-paclitaxel and gemcitabine groups were selected.

Figure 2.

Kaplan-Meier curves of (a) overall survival and (b) progression-free survival in patients who received gemcitabine plus nab-paclitaxel (solid line) and those who received gemcitabine monotherapy (broken line) as first-line treatment. The median overall survival was 12.2 months (95% CI, 7.1-not evaluable) and 9.4 months (95% CI, 6.6-12.5) in the gemcitabine plus nab-paclitaxel (GnP) and gemcitabine monotherapy (Gem) groups, respectively. The hazard ratio of overall survival was 0.65 (95% CI, 0.37-1.13; P = .120). The median progression-free survival was 9.2 months (95% CI, 5.9-16.1) and 3.7 months (95% CI, 2.8-5.7) in the GnP and Gem groups, respectively. The hazard ratio of progression-free survival was 0.38 (95% CI, 0.23-0.64; P = .0002).

Figure 3.

Subgroup analysis of the geriatric assessment for overall survival. The hazard ratios of overall survival of gemcitabine plus nab-paclitaxel and gemcitabine monotherapy in (a) Geriatric 8, (b) the instrumental activity of daily living, (c) Charlson comorbidity index, and (d) Mini-COG score were calculated.

Figure 4.

(a) Hazard ratio of overall survival in patients with higher G8 scores compared with those with lower scores. Using a cutoff value of 11 points resulted in 74 and 109 patients with higher and lower scores, respectively. The hazard ratio was 0.79 (95% CI, 0.54-1.16) in the higher score group, when compared with that in the lower score group. (b) Comparison of the overall survival between patients who received gemcitabine plus nab-paclitaxel and those who received gemcitabine monotherapy in the propensity score-matched analysis set. The hazard ratios for gemcitabine plus nab-paclitaxel compared with gemcitabine monotherapy were 0.51 (95% CI, 0.23-1.15) and 0.99 (95% CI, 0.45-2.19) in patients with a G8 score of >11 points (right) and those with a G8 score ≤11 points (left), respectively.