Geriatric Vulnerabilities and QOL Scores Predict OS in Metastatic PDAC
Baseline geriatric assessment vulnerabilities and quality of life scores correlate with overall survival in patients with metastatic pancreatic ductal adenocarcinoma receiving chemotherapy.
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Data presented at the 2025 ASCO Gastrointestinal Cancer Symposium showed that baseline geriatric assessment (GA) vulnerabilities and quality of life (QOL) scores were associated with overall survival (OS) in adults with metastatic pancreatic ductal adenocarcinoma (PDAC) receiving chemotherapy.
Data from the presentation is based on results from the phase 2 ECOG-ACRIN EA2186 (GIANT) trial (NCT04233866), which revealed a correlation between GA/QOL and OS related to 4 significant factors through multivariate analysis: Instrumental Activities of Daily Living (IADL) scale (HR, 0.85; P = .073), nutrition (HR, 0.86; P = .0039), depression (HR, 1.07; P = .029), and Functional Assessment of Cancer Therapy–Hepatobiliary (FACT-HEP; HR, 0.99; P = .026). Furthermore, white blood cell counts (HR, 0.29; P = .0023), depression (HR, 1.27; P = .0077), and BMI (HR, 1.10; P = .012) all significantly correlated with grade 3 toxicity incidence in a multi-variate analysis.
“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,” Efrat Dotan, MD, executive medical director of the Ann B. Barshinger Cancer Institute at Lancaster General Health of the University of Pennsylvania, stated in the presentation.1 “There is a strong correlation based on nutritional status, [IADL] function, depression, and every single one of the [QOL] measures. This is the first prospective study to evaluate [these measures] strongly. We hope that supportive care and management of these vulnerabilities will help improve outcomes of these patients and help us select who can derive benefit [from chemotherapy].”
Patients 70 years or older with untreated metastatic PDAC were selected to undergo a screening GA. Patients who were identified as vulnerable, or having mild to moderate GA abnormalities, were then given a complete geriatric and QOL assessment before being randomly assigned to receive either modified gemcitabine plus nab-paclitaxel or 5-flouorouracil (5FU) plus leucovorin and liposomal irinotecan every 2 weeks. Treatment continued until disease progression or intolerance; disease evaluation, a modified GA, and a QOL assessment were performed every 8 weeks.
Patients in the gemcitabine/nab-paclitaxel arm received intravenous gemcitabine and nab-paclitaxel separately over 30 minutes on day 1 of every 14-day cycle.2 Those in the alternative arm received intravenous fluorouracil over 46 hours starting day 1, as well as intravenous leucovorin over 90 to 120 minutes and intravenous liposomal irinotecan over 90 minutes on day 1 of every 14-day cycle.
For the gemcitabine/nab-paclitaxel (n = 88) and 5FU/liposomal irinotecan arms (n = 88) of the analysis, most patients had an ECOG performance status of 1 (64.8% vs 62.5%; P = .974). Additionally, 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. Furthermore, most patients had 1 vulnerability domain (60.9% vs 49.4%), with 6.9% and 11.5% of the respective arm 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). Additionally, 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). For the QOL FACT-HEP score, with scores ranging from 0 to 180, the median patient score was 130.5 (range, 74-175), including 129.5 (range, 74-172) in the gemcitabine arm and 132.5 (range, 77-175) in the 5FU arm.
The primary end point of the study was OS. Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). Furthermore, additional secondary end points included 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). Additionally, median PFS was 3.0 months (95% CI, 1.9-4.3) and 2.4 months (95% CI, 1.9-3.7) in each respective arm (HR, 1.10; 95% CI, 0.79-1.53; P = .58). An additional OS analysis revealed that patients who received 4 or more weeks of treatment had a median OS of 8.0 months (95% CI, 5.9-10.0) across cohorts.
