Treatment Of Metastatic Pancreatic Cancer Research Articles

Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer.

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

Treatment of metastatic pancreatic cancer: 25 years of innovation with little progress for patients

Treatment of metastatic pancreatic cancer: 25 years of innovation with little progress for patients

Comparison between different therapeutic sequences in patients affected by metastatic pancreatic ductal adenocarcinoma.

674 Background: The first-line treatment of metastatic pancreatic cancer involves different therapeutic regimens, among them, mFOLFIRINOX and gemcitabine-nabpaclitaxel. However, it remains to be clarified which sequence might correlate with better outcomes. The aim of our work was to evaluate which sequence leads to better overall survival in this setting. Methods: We retrospectively collected data from 358 patients affected by stage IV pancreatic ductal adenocarcinoma from 3 different Italian Institutions. Patients received mFOLFIRINOX or gemcitabine plus nabpaclitaxel as first-line chemotherapy, followed by a second-line non-cross-resistant chemotherapy (gemcitabine or fluoropyrimidine-based combinations). Survival distribution was assessed by Kaplan-Meier curves. The primary endpoint was median overall survival. Statistical analysis was performed with MedCalc package. Results: The median age was 66 (± 9), 195 (54,4%) were male and 163 (45,6%) were female. 292 (81,5%) patients start gemcitabine plus nabpaclitaxel as first line treatment, while 66 (18,5%) patients start mFOLFIRINOX first-line therapy. No statistically significant differences in terms of mOS were observed between the two mFOLFIRINOX and gemcitabine-nabpaclitaxel groups: 16 versus 15 months, respectively, p = 0,2). No significant differences were found in terms of mPFS either: 7 versus 8 months, respectively, p = 0,3). Conclusions: The results of our retrospective study showed no statistically significant survival advantage between the sequences starting with mFOLFIRINOX or with gemcitabine-nabpaclitaxel. Further studies will be necessary to establish the effectiveness of new therapeutic schemes to be introduced into clinical practice in order to define a better therapeutic algorithm.

Alternating application of gemcitabine/nab-paclitaxel (Gem/nab-Pac) and Gem monotherapy or continuous application of Gem/nab-Pac after induction treatment for first-line treatment of metastatic pancreatic cancer (mPC): First results from the randomized phase 2 ALPACA study from the German AIO study group (AIO-PAK-0114).

605 Background: The aim of the ALPACA study was to investigate whether improved overall tolerability accompanied by prolonged treatment duration and increased efficacy can be achieved by alternating treatment cycles of Gem/nab-Pac and Gem monotherapy compared to standard continuous Gem/nab-Pac after a 3-month induction phase in patients with mPC. Methods: The randomized, multicenter phase 2 ALPACA trial of the German AIO study group enrolled patients with confirmed mPC in the first-line setting. After an induction phase with 3 cycles of standard dose Gem/nab-Pac (Gem 1000 mg/m2 and nab-Pac 125 mg/m2 on d1, 8, 15 of each 28-day cycle), patients were randomized (1:1) either to continue treatment with standard Gem/nab-Pac, or to receive alternating cycles of standard dose Gem/nab-Pac combination therapy and Gem monotherapy (Gem 1000 mg/m2 on d1, 8, 15 of each 28-day cycle). Primary study endpoint was overall survival (OS) after randomization. The trial was registered with ClinicalTrials.gov, NCT02564146. Results: Between May 2016 and May 2021, 325 patients were enrolled from 29 German centers. 6 of the enrolled patients did not start treatment within the study. Following 3 cycles of induction treatment, 174 patients (53.5%) could be randomized. Main reasons for premature dropout were death (24.8%), progression of disease (22.8%), and adverse events (15.9%). Median OS after randomization in the alternating treatment arm was comparable to the standard treatment arm (10.5 vs. 10.4 months; HR 0.903, 80% CI 0.723-1.128, p=0.5551). Likewise, median progression-free survival was comparable in both arms (5.5 vs. 5.3 months; HR 0.767, 95% CI 0.556-1.056, p=0.1017). Tolerability was improved for mPC patients treated with alternating cycles compared to standard therapy, especially regarding peripheral neuropathy (all grades, 44.7% vs. 52.5%), and occurrence of infections (all grades, 29.4% vs. 47.5%). Treatment duration after randomization was similar in both arms (3.25 vs. 3.02 months). Fewer patients receiving alternating treatment cycles dropped out of the study due to adverse events compared to patients treated with continuous Gem/nab-Pac (14.9% vs 27.5%). In return, these patients terminated the study slightly more often due to progression of disease (48.3% vs 42.5%). Conclusions: The ALPACA trial suggests that a dose-reduced regimen with alternating cycles of Gem/nab-Pac and Gem monotherapy after 3 induction cycles of standard Gem/nab-Pac is feasible and associated with an OS comparable to standard treatment while resulting in improved tolerability. Clinical trial information: NCT02564146 .

Metastatic Pancreatic Cancer: Where Are We?

Pancreatic cancer is one of the most lethal neoplasms worldwide; it is aggressive in nature and has a poor prognosis. The overall survival rate for pancreatic cancer is low. Most patients present non-specific symptoms in the advanced stages, which generally leads to late diagnosis, at which point there is no option for curative surgery. The treatment of metastatic pancreatic cancer includes systemic therapy, in some cases radiotherapy, and more recently, molecular targeted therapies, which can positively impact cancer control and improve quality of life. This review provides an overview of the molecular landscape of pancreatic cancer based on the most recent literature, as well as current treatment options for patients with metastatic pancreatic cancer.

Abstract C084: iExplore: A phase I study of mesenchymal stem cell derived exosomes with KrasG12D siRNA for metastatic pancreas cancer patients harboring the KrasG12D mutation

Abstract Introduction The safety, target engagement, and benefit of iExosomes, short interfering RNA targeting KrasG12D encapsulated within exosomes and intravenously administered, were explored in patients with advanced pancreatic cancer harboring a KrasG12D mutation. Methods The initial phase I protocol was a conventional 3+3 design with three escalating dose levels (levels 1-3) of iExosomes, defined as exosomal protein levels and containing equal amounts of siRNA. Lack of toxicity at the highest dose level subsequently guided protocol amendment to an adaptive design exploring further dose escalation, with one patient treated at each additional dose level (levels 4-6). The highest dose level safely tolerated would be considered the optimal biological dose (OBD). Treatments were administered over three consecutive 14-day cycles. Blood was collected from all patients to assess changes in KrasG12D circulating DNA in response to treatment. Pre and post treatment biopsies were obtained from patients treated at dose levels 4-6 to evaluate target engagement, including changes in phosphorylated ERK levels by immunohistochemistry. Results Twelve patients received multiple iExosome treatments at specified dose levels, and none experienced any related adverse events of any grade. No dose limiting toxicities were observed, and the OBD was determined to be 28.8 mg of iExosome protein, administered in 6 infusions. Levels of circulating KrasG12D DNA decreased over the course of therapy. Levels of phosphorylated ERK in tumor biopsies decreased while on treatment, dropping to undetectable levels in higher dose levels. Clinically, the best response observed was stable disease as per RECISTv1.1 criteria in three patients, one each at dose levels 1-3. Conclusions iExosome therapy targeting KrasG12D is a safe and well-tolerated treatment for metastatic pancreatic cancer. Decrease in levels of circulating KrasG12D DNA and suppression of downstream Kras signaling phosphorylated ERK in tissue biopsies support effective target engagement of iExosomes in patients. Considering preclinical studies that indicate iExosome treatment enhances immune mediated anti-tumor responses, a future trial design will explore iExosomes at the OBD in combination with immune checkpoint inhibition for the treatment of pancreatic cancer. Citation Format: Brandon G. Smaglo, Valerie S. LeBleu, J. Jack Lee, Anirban Maitra, Raghu Kalluri, Katy Rezvani, Luisa M. Solis Soto, Mark Hurd, Indreshpal Kaur, Mayela C. Mendt Vilchez, Michelle L. Kirtley, Stacy L. Shaftoe, Maria Pia Morelli, Michael J. Overman, Dan Zhou, Robert A. Wolff, Janet Tu, Jason A. Willis, Ryan W. Huey, Michael S. Lee, Priya R. Bhosale, Suzanne W. Dworsky, Li Xu, Shubham Pant, Elizabeth J. Shpall. iExplore: A phase I study of mesenchymal stem cell derived exosomes with KrasG12D siRNA for metastatic pancreas cancer patients harboring the KrasG12D mutation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C084.

SY14-2 Current status of first-line treatment of metastatic pancreatic cancer

SY14-2 Current status of first-line treatment of metastatic pancreatic cancer

Systemic therapy for metastatic pancreatic cancer

Pancreatic cancer is an aggressive disease with an extremely unfavorable prognosis. The only effective method of treatment for this cancer is chemotherapy. The introduction of combined chemotherapy regimens and the development of molecular oncology in recent years have changed approaches to the treatment of this tumor. This review presents current literature data, as well as the data from the N. N. Blokhin National Medical Research Center of Oncology, concerning modern aspects of the treatment for metastatic pancreatic cancer.

Third-line treatment options in metastatic pancreatic cancer patients: a real-world study.

There are currently no standard therapy regimens for the third-line treatment of metastatic pancreatic cancer (mPC) patients. The aim of the present study was to compare the efficacy and safety of different third-line therapy regimens for mPC in the real-world. This study retrospectively analyzed mPC patients admitted to Zhejiang Provincial People's Hospital between June 2013 and January 2023. All patients' diagnoses were pathologically confirmed and their treatment was continued after the second-line therapy failed. The primary study endpoints included median overall survival (mOS), median progression-free survival (mPFS), and disease control rate (DCR). A total of 72 patients were enrolled in the study. Of these, 36 patients received chemotherapy alone, 16 received chemotherapy combined with targeted therapy or immunotherapy, 14 received chemotherapy-free antitumor therapy, and six received palliative care. The mPFS value for these groups was 4.40 months, 5.20 months, 2.33 months, and 0.80 months, respectively. The mOS value was 6.90 months, 5.90 months, 3.33 months, and 0.80 months, respectively. The DCR was 33.4%, 31.3%, 21.4%, and 0.0%, respectively. Overall, there were significant differences in prognosis between the palliative care group and the other treatment groups (mOS, P < 0.001; mPFS P < 0.001; DCR, P < 0.001). The differences among the mPFS, mOS, and DCR for different antitumor therapy regimens were not statistically significant. Compared to the chemotherapy alone group, the chemotherapy combined with targeted therapy or immunotherapy group experienced more adverse events (100% vs. 75.0%; P = 0.002). Chemotherapy combined with targeted therapy or immunotherapy was associated with a higher risk of grade 3/4 hyperaminotransferemia compared to chemotherapy alone (31.3% vs. 0.0%; P = 0.020) and chemotherapy-free antitumor therapy (31.3% vs. 0.0%; P = 0.020). Third-line antitumor therapy can prolong the survival time of patients with mPC. Targeted therapy or immunotherapy failed to further improve survival benefits based on chemotherapy results. Patients who underwent the third-line treatment with good physical status and family history of cancer were independent prognostic factors for longer mOS. The sequencing of fluorouracil and gemcitabine in the front-line therapy did not affect third-line mOS.

Management of Metastatic Pancreatic Cancer-Comparison of Global Guidelines over the Last 5 Years.

Pancreatic cancer (PC) is usually diagnosed at an advanced stage of its development, which results in lower overall survival (OS). Prognosis is also poor even with curative-intent surgery. Approximately 80% of patients with localized PDAC have micrometastases at the time of diagnosis, which leads to a worse prognosis than in other cancers. The objective of this study is to present the progress in the treatment of metastatic pancreatic cancer based on the recommendations of oncological scientific societies, such as ESMO, NCCN, ASCO, NICE and SEOM, over the last 5 years. Combined FOLFIRINOX therapy is mostly a recommended therapy among patients with good performance statuses, while gemcitabine is recommended for more fragile patients as a first-line treatment. The newest guidelines suggest that molecular profiling of the tumor should be the first step in determining the course of treatment. The use of modern molecular therapies in patients with specific gene mutations should extend the survival of patients with this disease.

Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan as First-line Treatment for Metastatic Pancreatic Cancer.

Treatment of advanced pancreatic cancer with a single therapeutic at a maximal dose has been largely ineffective at increasing survival. Combination therapies are commonly studied but often limited by toxicity. We previously showed that low-dose multiagent therapy with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), and cisplatin (GTX-C) was safe, well tolerated, and effective (NCT01459614). Here, we hypothesize that adding irinotecan to GTX-C may improve survival with minimal toxicity. Patients with treatment-naïve metastatic pancreatic adenocarcinoma were treated with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), cisplatin, and irinotecan (GTX-CI). Treatment consisted of capecitabine 500 mg twice daily on days 1-14 and gemcitabine 300 to 500 mg/m2, docetaxel 20 mg/m2, cisplatin 15 to 20 mg/m2, and irinotecan 20 to 60 mg/m2 on days 4 and 11 of a 21-day cycle. The primary objective was 9-month overall survival (OS). Secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and OS. The regimen was well tolerated. The recommended phase II dose was gemcitabine 500 mg/m2, docetaxel 20 mg/m2, capecitabine 500 mg po bid, cisplatin 20 mg/m2, and irinotecan 20 mg/m2. Median follow-up in phase II was 11.02 months (2.37-45.17). Nine-month OS rate was 57% [95% confidence interval (CI): (41-77)]. RR was 57% [95% CI: (37-75) 50% PR and 7% CR]. DCR was 87% [95% CI: (69-96)]. Median OS and PFS were 11.02 [95% CI: (8.54-21.09)] and 8.34 [95% CI: (6.34-NA)] months, respectively. The addition of irinotecan to GTX-C was safe and well tolerated. While the study did not meet its primary objective, the responses were clinically meaningful using a well-tolerated regimen. We aimed to optimize the previously reported efficacious regimen of low-dose multiagent therapy with GTX-C for the treatment of metastatic pancreatic ductal adenocarcinoma by adding irinotecan. The primary objective was not met, but GTX-CI was well tolerated. The RR of 57%, median PFS of 8.3 months, median OS of 11 months, and 36-month OS rate of 19% suggest clinical benefit. Further optimization of this regimen is warranted.

Maintenance Treatment for Metastatic Pancreatic Cancer: Balancing Therapeutic Intensity with Tolerable Toxicity.

Metastatic pancreatic ductal adenocarcinoma is typically treated with multi-agent chemotherapy until disease progression or intolerable cumulative toxicity. For patients whose disease shows ongoing control or response beyond a certain timeframe (≥3-4 months), options include pausing chemotherapy with close monitoring or de-escalating to maintenance therapy with the goal of prolonging progression-free and overall survival while preserving quality of life. There is currently no universally accepted standard of care and a relative dearth of randomized clinical trials in the maintenance setting. Conceptually, such therapy can entail continuing the least toxic components of a first-line regimen and/or introducing novel agent(s) such as the poly(ADP-ribose) polymerase inhibitor olaparib, which is presently the only approved drug for maintenance treatment and is limited to a genetically defined subset of patients. In addition to identifying new therapeutic candidates and combinations in the maintenance setting, including targeted agents and immunotherapies, future research should focus on better understanding this unique biologic niche and how treatment in the maintenance setting may be distinct from resistant/refractory disease; identifying molecular predictors for more effective pairing of specific treatments with patients most likely to benefit; and establishing patient-reported outcomes in clinical trials to ensure accurate capture of quality of life metrics.

Comparison of different second line treatments for metastatic pancreatic cancer: a systematic review and network meta-analysis

BackgroundIn metastatic pancreatic ductal adenocarcinoma (mPDAC), first line treatment options usually include combination regimens of folinic acid, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX or mFOLFIRINOX) or gemcitabine based regimens such as in combination with albumin-bound paclitaxel (GEM + nab-PTX). After progression, multiple regimens including NALIRI + 5-FU and folinic acid, FOLFIRINOX, 5-FU-based oxaliplatin doublets (OFF, FOLFOX, or XELOX), or 5-FU-based monotherapy (FL, capecitabine, or S-1) are considered appropriate by major guidelines. This network meta-analysis (NMA) aimed to compare the efficacy of different treatment strategies tested as second-line regimens for patients with mPDAC after first-line gemcitabine-based systemic treatment.MethodsRandomized phase II and III clinical trials (RCTs) were included if they were published or presented in English. Trials of interest compared two active systemic treatments as second-line regimens until disease progression or unacceptable toxicity. We performed a Bayesian NMA with published hazard ratios (HRs) and 95%confidence intervals (CIs) to evaluate the comparative effectiveness of different second-line therapies for mPDAC. The main outcomes of interest were overall survival (OS) and progression free survival (PFS), secondary endpoints were grade 3–4 toxicities. We calculated the relative ranking of agents for each outcome as their surface under the cumulative ranking (SUCRA). A higher SUCRA score meant a higher ranking for efficacy outcomes.ResultsA NMA of 9 treatments was performed for OS (n = 2521 patients enrolled). Compared with 5-FU + folinic acid both irinotecan or NALIRI + fluoropyrimidines had a trend to better OS (HR = 0.76, 95%CI 0.21–2.75 and HR = 0.74, 95%CI 0.31–1.85). Fluoropyrimidines + folinic acid + oxaliplatin were no better than the combination without oxaliplatin. The analysis of treatment ranking showed that the combination of NALIRI + 5-FU + folinic acid was most likely to yield the highest OS results (SUCRA = 0.7). Furthermore, the NMA results indicated that with the highest SUCRA score (SUCRA = 0.91), NALIRI + 5-FU + folinic acid may be the optimal choice for improved PFS amongst all regimens studied.ConclusionsAccording to the NMA results, NALIRI + 5-FU, and folinic acid may represent the best second-line treatment for improved survival outcomes in mPDAC. Further evidence from prospective trials is needed to determine the best treatment option for this group of patients.

Racial disparities in the treatment of metastatic pancreatic cancer using 5-fluorouracil (5-FU) vs. gemcitabine-based combination chemotherapy: A single-institutional analysis.

e16292 Background: Metastatic pancreatic adenocarcinoma is very aggressive with poor prognosis for which 5-FU or gemcitabine-based combination chemotherapy remains the first-line treatment. In a meta-analysis by Rong Tang et al., gemcitabine-based treatment was non-inferior to 5-FU. Treatments are usually selected based on the patient's tolerability and side effect profile. This study aims at studying the outcomes after treatment of metastatic pancreatic adenocarcinoma with 5-FU versus gemcitabine-based therapy in the Caucasian and African American (AA) population. Methods: All patients &gt; 18 years of age with metastatic pancreatic adenocarcinoma who received palliative chemotherapy at the LCMC health system between January 2015- January 2021 were extracted from EPIC EMR through Slicer Dicer. Information was obtained about the type of treatment, progression, and associated comorbidities. Multivariable Cox regression was performed to determine whether 5-FU or Gemcitabine-based treatment was superior in terms of progression-free survival and overall survival from the start of treatment after adjusting for covariates like race, gender, age, and comorbidities. Patients who stopped treatment for any reason other than progression/death were considered censored at that time. Deviance-based tests were used to determine whether there was a race/treatment interaction. Results: 116 patients were included in the analysis, of which 52.9% used Gemcitabine, 54.3% were AA, and 50% identified as male. The average age, BMI, and number of comorbidities were 65.7, 25.3, and 1.8, respectively. AA patients were slightly more likely to receive first-line gemcitabine (62.2% vs. 44.4%, p = .064) and cox regression showed no relationship between treatment and PFS (p = .25) nor race (p = .507). When adding an interaction term between race/treatment, there was some evidence that an interaction was needed (p = .065). In this model, 5FU showed a decreased hazard of PFS in Caucasian patients compared to gemcitabine (adjusted Hazard Ratio = .43, 95% CI = .2-.95, p = .036), however the treatment effect in AA patients was non-significant (aHR = 1.19, 95% CI = .87-1.63, p = .28). In the subset of patients with at least 1 month of treatment (n = 94), patients who received 5-FU based treatment first had a significant increase in overall survival (aHR = .57, 95% CI = .34-.96), while AA patients had increased but not significant survival (aHR = .64, p = .075). There was no interaction between treatment and race (p = .66). Conclusions: Our study showed an increase in PFS in 5-FU-based treatment in Caucasian patients compared to Gemcitabine. AA patients were more likely to receive Gemcitabine-based therapy first, but no difference was noted in the PFS. 5-FU-based treatment significantly increased the overall survival when compared to gemcitabine in the whole cohort.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer

ObjectiveDNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC. Patients and MethodsPatients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. Results130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48–9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04–3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13–5.48, p = 0.023) and high post-operative CA 19–9 level (>100 IU/ml) (HR:2.61 95% CI 1.40–4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53. ConclusionContrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

The efficacy and safety of Nab-paclitaxel plus gemcitabine versus mFOLFIRINOX in the first-line treatment of metastatic pancreatic cancer: a retrospective study

BackgroundNab-paclitaxel plus gemcitabine (AG) and modified FOLFIRINOX (FFX) are two systemic therapies that have been widely used as standard first-line chemotherapy regimens in metastatic pancreatic cancer. However, since there is no clinical trial to directly compare the efficacy and safety of the two regimens, it is not clear which regimen is more effective. In this study, we aim to examine and compare the efficacy and safety of AG and FFX as first-line chemotherapy regimens in Chinese patients with metastatic pancreatic cancer in a real-world setting.MethodsWe retrospectively evaluated the outcomes of 44 patients who were diagnosed with metastatic pancreatic cancer and were treated with either AG (n = 24) or FFX (n = 20) as first-line chemotherapy between March 2017 and February 2022 at Zhongnan Hospital of Wuhan University. Prognostic nutrition index (PNI) was calculated based on the serum albumin level and peripheral lymphocyte count. According to the optimal cutoff value of PNI, patients were divided into low PNI group (PNI < 43.70) and high PNI group (PNI ≥ 43.70).ResultsOf 44 patients in this study, 24 were treated with AG, and 20 were treated with FFX as first-line chemotherapy. No significant differences in baseline characteristics were found between the two groups. The objective response rate (ORR) was 16.7% in the AG group and 20.0% in the FFX group. The disease control rate (DCR) was 70.8% in the AG group and 60.0% in the FFX group. There was no significant difference in PFS or OS between the AG group and the FFX group. The median progression-free survival (PFS) was 4.67 months (95% confidence interval [CI], 2.91–6.42) in the AG group and 3.33 months (95% CI, 1.87–4.79, p = 0.106) in the FFX group. The median overall survival (OS) was 9.00 months (95% CI, 7.86–12.19) in the AG group and 10.00 months (95% CI, 7.70–12.27, p = 0.608) in the FFX group. The second-line treatment rate was 62.5% in the AG group and 55.0% in the FFX group. Immune checkpoint inhibitors (ICIs) based regimens are common second-line treatment options whether in AG or FFX group. Significantly more grade 3–4 peripheral neuropathy occurred in the AG than FFX groups (4 (20.8%) vs 0 (0.0%), p = 0.030*). The patients in the PNI (Prognostic nutrition index) ≥ 43.7 group had a significant longer median OS (PNI ≥ 43.7 vs PNI < 43.7: 10.33 vs 8.00 months, p = 0.019).ConclusionAG and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer. Pancreatic cancer patients receiving first-line chemotherapy with good nutritional status are likely to have a better prognosis.

Addition and timing of surgery in multiagent chemotherapy treatment of metastatic pancreatic cancer

Background: Most pancreatic cancer patients have metastasis at diagnosis and even limited metastatic burden is considered a contraindication to surgery. Modern multiagent chemotherapy regimens have challenged the dogma of unresectable disease in locally advanced pancreatic cancer. We aimed to evaluate survival in surgically treated metastatic pancreatic cancer with preoperative versus postoperative multiagent chemotherapy using data from the National Cancer Database.

Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects

Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.

The effectiveness of nab-paclitaxel plus gemcitabine and gemcitabine monotherapy in first-line metastatic pancreatic cancer treatment: A real-world evidence.

Pancreatic cancer is one of the most lethal malignancies with a rise in mortality rates. FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. Both protocols are now considered the standard of first-line treatment with no significant difference between them, primarily based on observational studies. Although new therapeutic options have emerged recently, the prognosis remains poor. We conducted a retrospective single-center study on 139 patients treated for metastatic pancreatic adenocarcinoma (mPDAC) with gemcitabine monotherapy (Gem) or nab-paclitaxel + gemcitabine (Nab-P/Gem) in the first line. The aim of our study was to evaluate the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) as well as the influence of patient and disease characteristics on outcomes. Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 months, respectively, but without reaching statistical significance. Furthermore, the 6-month survival in the Nab-P/Gem group was also higher, 78.1% versus 47.8%. In terms of survival, the group of elderly patients, patients of poorer performance, with higher metastatic burden and liver involvement, benefited the most from combination therapy. In our analysis ECOG performance status (p.s.), previous primary tumor surgery, and liver involvement were found to be independent prognostic factors. The addition of nab-paclitaxel to gemcitabine resulted in a significant improvement in the OS of patients with mPDAC. Subgroup analysis demonstrated that patients with some unfavorable prognostic factors benefited the most.

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer.

BACKGROUNDGemcitabine plus nab-paclitaxel (GA) is a commonly used first-line treatment regimen for metastatic pancreatic cancer, and many studies will add a novel targeted agent to this regimen for improving patient survival rate. However, the clinical effectiveness of GA is the most controversial issue. AIMTo compare the efficacy and safety of GA regimen with a targeted agent and GA regimen.METHODSUp to 1 December 2021, the eligible randomized controlled trials (RCTs) relating to GA and GA with a targeted agent were searched on PubMed, EMBASE and Cochrane Library for eligible data. We screened out appropriate studies for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity, which had been pooled and finally analyzed by using Stata version 15.1. In addition, we use Reference Citation Analysis (https://www.referencecitationanalysis.com/) to collect the latest related literature to improve the latest cutting-edge research results.RESULTSSeven RCTs involving 1544 patients (848 men and 696 women) were included. There were no significant differences between GA with a targeted agent and GA in PFS [hazard ratio (HR): 1.18 95% confidence interval (CI): 0.91-1.53], OS (HR: 1.12 95%CI: 0.99-1.27), and ORR (HR: 0.96 95%CI: 0.71-1.29). There was no notable difference in the two groups in grade 3/4 toxicity (fatigue, anemia, vomiting and neutropenia), whereas the incidence of grade 3/4 diarrhea considerably increased in GA with a targeted drug.CONCLUSIONAdding a novel targeted agent to the GA regimen did not improve survival rate of patients with metastatic pancreatic cancer.