Data presented at the 2025 ASCO Gastrointestinal Cancers Symposium highlights the impact of baseline geriatric assessment (GA) vulnerabilities and quality of life (QOL) scores on overall survival (OS) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) undergoing chemotherapy. The findings come from the phase 2 ECOG-ACRIN EA2186 (GIANT) trial (NCT04233866).
The GIANT trial, the first elderly-specific clinical trial evaluating chemotherapy in vulnerable adults with metastatic pancreatic cancer, demonstrated that baseline GA and QOL scores significantly affect outcomes. Multivariate analysis revealed a correlation between GA/QOL and OS related to several significant factors:
- Instrumental Activities of Daily Living (IADL) scale (HR, 0.85; P = .073)
- Nutrition (HR, 0.86; P = .0039)
- Depression (HR, 1.07; P = .029)
- Functional Assessment of Cancer Therapy–Hepatobiliary (FACT-HEP; HR, 0.99; P = .026)
Additionally, white blood cell counts (HR, 0.29; P = .0023), depression (HR, 1.27; P = .0077), and BMI (HR, 1.10; P = .012) significantly correlated with grade 3 toxicity incidence in a multi-variate analysis.
Study Design and Patient Population
The study enrolled patients 70 years or older with untreated metastatic PDAC. These patients underwent a screening GA, and those identified as vulnerable or having mild to moderate GA abnormalities received a complete geriatric and QOL assessment. Participants were then randomized to receive either modified gemcitabine plus nab-paclitaxel or 5-flouorouracil (5FU) plus leucovorin and liposomal irinotecan every two weeks. Treatment continued until disease progression or intolerance, with disease evaluation, a modified GA, and a QOL assessment performed every eight weeks.
Patients in the gemcitabine/nab-paclitaxel arm received intravenous gemcitabine and nab-paclitaxel over 30 minutes on day 1 of every 14-day cycle. The alternative arm received intravenous fluorouracil over 46 hours starting day 1, along with intravenous leucovorin over 90 to 120 minutes and intravenous liposomal irinotecan over 90 minutes on day 1 of every 14-day cycle.
Key Findings
For the gemcitabine/nab-paclitaxel (n = 88) and 5FU/liposomal irinotecan arms (n = 88), most patients had an ECOG performance status of 1 (64.8% vs 62.5%; P = .974). Screening vulnerability consisted of 36.4% and 36.4% for age, 28.4% and 36.4% for co-morbidities, 41.4% and 49.4% for cognition, and 20.7% and 18.4% for IADL in the respective arms. Most patients had 1 vulnerability domain (60.9% vs 49.4%), with 6.9% and 11.5% having 3 or more domains.
Pretreatment BMI was 25.6 (range, 15.7-44.1) across cohorts, including 25.9 (range, 17.9-44.1) in the gemcitabine arm and 24.7 (range, 15.7-43.8) in the 5FU arm (P = .046). The median weight loss was 14.0 lbs (range, 0-95), including 14.5 lbs (0-62) in the gemcitabine arm and 12.6 lbs (range, 0-95) in the 5FU arm (P = .812). The median QOL FACT-HEP score was 130.5 (range, 74-175).
The primary endpoint of the study was OS. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR), along with QOL and toxicities of interest for older adults.
The median OS in the gemcitabine arm was 4.7 months (95% CI, 4.1-7.4) vs 4.4 months (95% CI, 3.1-8.9) in the 5FU arm (HR, 1.12; 95% CI, 0.76-1.66; P = .72). Median PFS was 3.0 months (95% CI, 1.9-4.3) and 2.4 months (95% CI, 1.9-3.7) in each arm, respectively (HR, 1.10; 95% CI, 0.79-1.53; P = .58). Patients receiving 4 or more weeks of treatment had a median OS of 8.0 months (95% CI, 5.9-10.0) across cohorts.
Clinical Implications
According to Dr. Efrat Dotan, executive medical director of the Ann B. Barshinger Cancer Institute at Lancaster General Health of the University of Pennsylvania, “The GIANT study was the first elderly-specific clinical trial [evaluating chemotherapy in vulnerable adults with metastatic pancreatic cancer], and it does show us what real outcomes vulnerable patients have with these treatments. Baseline [GA] and [QOL] scores clearly affect outcomes.”
Dr. Dotan emphasized the strong correlation between nutritional status, IADL function, depression, and QOL measures. She expressed hope that supportive care and management of these vulnerabilities will improve patient outcomes and help identify individuals who can benefit from chemotherapy.
