Nab-Paclitaxel (Nab-P) Plus Gemcitabine (Gem) Vs Gem Alone for Patients (Pts) with Metastatic Pancreatic Cancer (Pc): Subgroup Analyses of the Mpact Trial Based on the Presence of Liver Metastases (Lms) and Number of Metastatic Sites

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

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The impact of modified Glasgow Prognostic Scale as a predictor of survival advantage by FOLFIRINOX in metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.440 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 440-440

Author(s):

Ikuhiro Yamada ◽

Masato Ozaka ◽

Ryo Kanata ◽

Kei Saito ◽

Takashi Sasaki ◽

...

Keyword(s):

Pancreatic Cancer ◽

Survival Time ◽

Survival Data ◽

Selection Criteria ◽

Response To Therapy ◽

Metastatic Pancreatic Cancer ◽

Lymphocyte Ratio ◽

Metastatic Sites ◽

The Impact ◽

Worse Prognosis

440 Background: The superiority of FOLFIRINOX (FFX) therapy over gemcitabine (Gem) alone in patients with metastatic pancreatic cancer (mPC) has been demonstrated in ACCORD11. However, this combination regimen is associated with relevant toxicity and predictors for response to therapy are warranted. The aim of this study is to determine the prognostic factors associated with an indication for FFX therapy in patients with mPC. Methods: The current study included data from all consecutive patients who were diagnosed as mPC at our hospital between September 2007 and December 2014. Selection criteria were as follows: patients who 1) had histologically confirmed pancreatic adenocarcinoma, 2) were diagnosed as having metastatic disease, and 3) received first-line chemotherapy with Gem alone or FFX. We examined the prognostic markers, such as derived neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, modified Glasgow prognostic scale (mGPS), ECOG Performance Status (PS), CA19-9 level and number of metastatic sites from the medical records and analyzed their survival data by chemotherapy regimen subgroups. Results: There were 187 patients who met the selection criteria. 159 (85%) received Gem alone, 28 (15%) received FFX. Univariate and multivariate regression analyses revealed that mGPS (1≦), number of metastatic sites (2≦) and high level of CA19-9 level (1000 U/ml≦) were significantly associated with worse prognosis in Gem group. PS (1≦) and mGPS (1≦) were significantly associated with worse prognosis in FFX group. Since mGPS was the only significant prognostic marker in both groups, we analyzed survival data stratified by regimen in both mGPS 0 or 1≦ cohort. In mGPS 0 cohort, the median survival time was 17.9 months in the FFX group as compared with 8.5 months in the Gem group (hazard ratio, 0.27; 95% CI, 0.11 to 0.55; P = 0.004). However there was no significant difference in mGPS 1≦ cohort (P = 0.4). Conclusions: This data suggests that mGPS 0 is associated with better survival time, and suggests it may also be predictive of benefit for FFX in Japanese patients with mPC. Incorporating mGPS into the clinical context may better inform prognosis and chemotherapy decisions in mPC patients.

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Immunohistochemical pattern of liver metastases and paired sample analysis in patients with metastatic pancreatic cancer: Pronounced CDX2 expression and loss of SMAD4 indicate poor survival

Pancreatology ◽

10.1016/j.pan.2019.05.284 ◽

2019 ◽

Vol 19 ◽

pp. S107

Author(s):

Thomas Held ◽

Caroline S. Verbeke ◽

Oliver Strobel ◽

Wiktor Rutkowski ◽

Christina Villard ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastases ◽

Metastatic Pancreatic Cancer ◽

Sample Analysis ◽

Poor Survival ◽

Paired Sample ◽

Cdx2 Expression

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The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16272 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16272-e16272

Author(s):

Jonathan O Hackett ◽

Rebecca S Crothers ◽

Emma Shaughnessy ◽

Giuseppe Cardaci ◽

Alaar Kaard ◽

...

Keyword(s):

Pancreatic Cancer ◽

Radiation Therapy ◽

Liver Metastases ◽

Metastatic Pancreatic Cancer ◽

Selective Internal Radiation Therapy ◽

Internal Radiation ◽

Prior Chemotherapy ◽

Selective Internal Radiation ◽

Internal Radiation Therapy ◽

Adenocarcinoma Of The Pancreas

e16272 Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.

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Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis

Gut ◽

10.1136/gutjnl-2021-325272 ◽

2022 ◽

pp. gutjnl-2021-325272

Author(s):

Gaia Bellomo ◽

Carolyn Rainer ◽

Valeria Quaranta ◽

Yuliana Astuti ◽

Meirion Raymant ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastases ◽

Disease Progression ◽

Metastatic Disease ◽

Ex Vivo ◽

Receptor Activation ◽

Tumour Cells ◽

Metastatic Pancreatic Cancer ◽

Metastatic Tumour ◽

Metastatic Liver

ObjectivePancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease and cytotoxic chemotherapy is the standard of care treatment for patients with advanced disease. Here, we investigate how the microenvironment in PDAC liver metastases reacts to chemotherapy and its role in metastatic disease progression post-treatment, an area which is poorly understood.DesignThe impact of chemotherapy on metastatic disease progression and immune cell infiltrates was characterised using flow and mass cytometry combined with transcriptional and histopathological analysis in experimental PDAC liver metastases mouse models. Findings were validated in patient derived liver metastases and in an autochthonous PDAC mouse model. Human and murine primary cell cocultures and ex vivo patient-derived liver explants were deployed to gain mechanistical insights on whether and how chemotherapy affects the metastatic tumour microenvironment.ResultsWe show that in vivo, chemotherapy induces an initial infiltration of proinflammatory macrophages into the liver and activates cytotoxic T cells, leading only to a temporary restraining of metastatic disease progression. However, after stopping treatment, neutrophils are recruited to the metastatic liver via CXCL1 and 2 secretion by metastatic tumour cells. These neutrophils express growth arrest specific 6 (Gas6) which leads to AXL receptor activation on tumour cells enabling their regrowth. Disruption of neutrophil infiltration or inhibition of the Gas6/AXL signalling axis in combination with chemotherapy inhibits metastatic growth. Chemotherapy increases Gas6 expression in circulating neutrophils from patients with metastatic pancreatic cancer and recombinant Gas6 is sufficient to promote tumour cell proliferation ex vivo, in patient-derived metastatic liver explants.ConclusionCombining chemotherapy with Gas6/AXL or neutrophil targeted therapy could provide a therapeutic benefit for patients with metastatic pancreatic cancer.

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