OverviewPancreatic cancer is one of the most common causes of cancer-related death among men and women in the United States. Abstract Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection. J Natl Compr Canc Netw 2017;15(8):1028-1061 doi: 10.6004/jnccn.2017 NCCN Categories of Evidence and Consensus Please NoteThe These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients’ advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

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IMPORTANCE Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1-expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC.OBJECTIVE To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC. DESIGN, SETTING, AND PARTICIPANTSIn this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis.INTERVENTIONS Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. MAIN OUTCOMES AND MEASURESThe primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events.RESULTS A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein-proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51; P < .001). The most common treatment-related grade 3 or 4 toxic effects were hyponatremia (3 of 54 [6%]) and increased alkaline phosphatase (2 of 54 [4%]).CONCLUSIONS AND RELEVANCE This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients.

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.

Although geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown.OBJECTIVE To assess whether specific geriatric assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer. DESIGN, SETTING, AND PARTICIPANTSA randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle.INTERVENTIONS Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration. MAIN OUTCOMES AND MEASURESThe primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation. RESULTS Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, −1.5 to −18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be con...

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

To broaden access to and implementation of precision medicine in the care of patients with pancreatic cancer, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multiomic profiling to determine molecularly rationalized clinical trials and off-label therapies. Tumor samples were obtained for 640 patients from 287 academic and community practices covering 44 states. College of American Pathologists/Clinical Laboratory Improvement Amendments-accredited laboratories were used for genomic, proteomic, and phosphoprotein-based molecular profiling. Tumor samples were adequate for next-generation sequencing in 96% and IHC in 91% of patients. A tumor board reviewed the results for every patient and found actionable genomic alterations in 50% of patients (with 27% highly actionable) and actionable proteomic alterations (excluding chemopredictive markers) in 5%. Actionable alterations commonly found were in DNA repair genes ( or mutations, 8.4%) and cell-cycle genes ( or alterations, 8.1%). A subset of samples was assessed for actionable phosphoprotein markers. Among patients with highly actionable biomarkers, those who received matched therapy ( = 17) had a significantly longer median progression-free survival (PFS) than those who received unmatched therapy [ = 18; PFS = 4.1 vs. 1.9 months; HR, 0.47; 95% confidence interval (CI): 0.24-0.94; = 0.03]. A comprehensive precision medicine system can be implemented in community and academic settings, with highly actionable findings observed in over 25% of pancreatic cancers. Patients whose tumors have highly actionable alterations and receive matched therapy demonstrated significantly increased PFS. Our findings support further prospective evaluation of precision oncology in pancreatic cancer. .