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TPS4590 Background: Only 5%-15% of patients (pts) with advanced bladder cancer attain long-term survival with standard first-line cisplatin-based chemotherapy. Programmed death 1 (PD-1)/PD-L1 inhibitors have proven effective in recurrent, advanced urothelial cancer. Emerging data suggest these agents may also be useful in the first-line setting. In KEYNOTE-052, first-line pembro, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in cisplatin-ineligible pts with advanced urothelial cancer. KEYNOTE-361 (NCT02853305) is a randomized, open-label, phase 3 study of pembro with or without chemotherapy versus chemotherapy alone in pts with advanced urothelial carcinoma. Methods: Key eligibility criteria include age ≥18 years; histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra; measurable disease (RECIST v1.1, investigator review); no prior systemic chemotherapy ([neo]adjuvant platinum-based chemotherapy with recurrence > 12 months after completion is allowed); ECOG PS 0-2; and provision of a tumor sample for biomarker analyses. Pts will be randomly assigned 1:1:1 to receive pembro 200 mg every 3 weeks (Q3W), pembro + investigator’s choice of chemotherapy (gemcitabine [1000 mg/m2 on day 1 and 8 Q3W] + cisplatin [70 mg/m2 Q3W]), or chemotherapy alone. Cisplatin-ineligible pts randomly assigned to chemotherapy will receive gemcitabine + carboplatin [AUC 5 Q3W]. Chemotherapy choice must be selected before randomization. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or 35 cycles of pembro (pembro arms only). Response will be assessed Q9W for the first year and Q12W thereafter. AEs will be evaluated throughout and graded per NCI CTCAE v4.0. Primary end points are progression-free survival (RECIST v1.1 per central review) and overall survival; secondary end points include objective response rate and safety and tolerability. Efficacy outcomes will be compared for pembro vs chemotherapy and pembro + chemotherapy vs chemotherapy. Enrollment is ongoing; ~990 pts will be enrolled. Clinical trial information: NCT02853305.

Purpose The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. Methods A cohort of 193 PDAC patients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. Results All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802-6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). Conclusion Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.