Prospective Phase II Trial of Biweekly Gemcitabine Plus Nab-Paclitaxel as First-Line Therapy in Patients Aged 75 Years and Older With Unresectable Pancreatic Cancer.

BACKGROUND: Although older adults (≥ 75 years) constitute a large proportion of patients with unresectable pancreatic cancer (PC), they remain underrepresented in clinical trials. Biweekly gemcitabine plus nab-paclitaxel (GnP) has been evaluated in retrospective studies as an alternative dosing schedule, whereas prospective evidence remains limited. AIMS: This single-center, prospective Phase II trial aimed to evaluate the efficacy and safety of biweekly GnP as a first-line therapy in older adults with unresectable PC. METHODS AND RESULTS: Eligible patients aged ≥ 75 years with histologically or cytologically confirmed unresectable pancreatic adenocarcinoma received GnP (1000 mg/m2 gemcitabine; 125 mg/m2 nab-paclitaxel) on days 1 and 15 of each 28-day cycle. The primary endpoint was the overall response rate (ORR). Key secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. A total of 17 patients were enrolled between August 2019 and March 2021 (median age, 77 years; 13 metastatic, 4 locally advanced). The ORR was 47.1% (8/17; 95% confidence interval [CI], 23.0%-72.2%), and the disease control rate was 82.4% (14/17). The median OS and PFS were 16.8 (95% CI, 5.9-24.6) and 8.3 (95% CI, 4.9-10.1) months, respectively. The 1- and 2-year survival rates were 58.8% and 29.4%, respectively. Grade ≥ 3 hematologic adverse events occurred in 17.6% of patients. Treatment-related adverse events led to treatment discontinuation in three patients: one case of interstitial pneumonia and two cases of peripheral sensory neuropathy. No treatment-related deaths occurred. CONCLUSION: Biweekly GnP showed promising antitumor activity in a selected population of patients aged ≥ 75 years with unresectable PC. Because enrollment ended before the planned sample size was reached, the study findings should be interpreted cautiously. TRIAL REGISTRATION: jRCTs051190038.