Routine prognostic blood tests to compare survival outcomes with low-dose therapy in treatment-naïve and resistant advanced pancreatic cancer.

e16349 Background: Patients with advanced pancreatic cancer (APC) have limited effective treatment options and substantial unmet needs. Prognostic blood tests (PBTs) may identify patients most likely to benefit from specific therapeutic strategies, including low-dose chemotherapy. Methods: Patients with treatment-naïve (NAPC) or resistant (RAPC) stage IV APC and ECOG performance status 0–2 were enrolled. RAPC tumors had progressed after FOLFIRINOX, gemcitabine with nab-paclitaxel, or both. Treatment consisted of one-third standard doses of gemcitabine, irinotecan, 24-hour fluorouracil/leucovorin, and day-2 oxaliplatin. Upon progression, docetaxel and mitomycin C were added on day 2 without discontinuing prior therapy. Written informed consent was obtained, and the study was registered with IRBs, the FDA, and ClinicalTrials.gov in accordance with Helsinki standards. This was a prospective, intent-to-treat analysis. Uni- and multivariate analyses evaluated survival and interactions based on established cut points for PBTs, age, sex, and treatment resistance. Results: Median survival time (MST) was 13.5 months (95% CI, 12–15) for 53 patients with NAPC and 9.4 months (95% CI, 7.1–10.9) for 53 patients with RAPC (p = 0.39). The A.L.A.N. score (AS 0–2), defined by fewer than three unfavorable tests; serum albumin < 3.5 g/dL, neutrophil-to-lymphocyte ratio ≥3, absolute neutrophil count > 8,000/µL, and lymphocyte-to-monocyte ratio < 2.1, was the most powerful prognostic indicator (p < 10⁻⁹). Among favorable NAPC PBT subgroups (77% of patients), MSTs ranged from 13.6 to 17.2 months, with 24-month survival rates of 24–35% (p = 0.03 to 2.3×10⁻⁷). Unfavorable NAPC subgroups had MSTs of 8–12.5 months. Favorable RAPC PBT subgroups (81% of patients) demonstrated MSTs of 12.5–18.2 months, with 12-month survival rates of 50–75% (p = 0.02 to 4.5×10⁻⁴). Unfavorable RAPC subgroups had MSTs exceeding 6–8 months. Treatment was well tolerated, with no hospitalizations, infections, treatment discontinuations, or dose-limiting toxicities. Conclusions: Low-dose chemotherapy may safely prolong survival in a majority of patients with NAPC identified by favorable PBTs, as well as in select patients with RAPC and A.L.A.N. scores of 0–2. Future trials integrating independent PBTs (serum albumin, NLR, ANC, LMR) and interactive biomarkers (platelets, monocytes, hemoglobin) may refine patient selection, expand eligibility for those with unmet needs, support lower-dose strategies, enable timely recombination and rechallenge, and improve understanding of host-cell–associated resistance mechanisms. Clinical trial information: 119005 .