Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System

Patel, Timil; Miccio, Joseph A.; Cecchini, Michael; Srikumar, Thejal; Stein, Stacey; Kortmanksy, Jeremy; Johung, Kimberly L.; Lacy, Jill

doi:10.21037/jgo-21-202

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…Here, the FFX group exhibited a median survival of 15.00 months, surpassing the previously recorded survival of 11.1 months [ 3 ], whereas the GnP group demonstrated a median survival of 11.04 months, also exceeding the previously recorded survival of 8.5 months [ 4 ]. In particular, FFX outperformed GnP significantly, which is consistent with many previous studies [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, some studies did not consider performance status at all [ 11 , 12 , 13 ], and others had very small numbers of patients included [ 11 , 13 , 15 ].…”

Section: Discussionsupporting

confidence: 92%

“…In particular, FFX outperformed GnP significantly, which is consistent with many previous studies [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, some studies did not consider performance status at all [ 11 , 12 , 13 ], and others had very small numbers of patients included [ 11 , 13 , 15 ]. Performance status is a factor that must be considered, as it has a significant impact on the selection of initial chemotherapy regimens.…”

Section: Discussionsupporting

confidence: 92%

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The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data

Jang,

Kim,

Lee

et al. 2024

JCM

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Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206–1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612–0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597–0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data

Jang,

Kim,

Lee

et al. 2024

JCM

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“… 11 , 12 No randomized phase III study neither compared FOLFIRINOX versus GEM-NAB directly, but retrospective studies showed a trend toward greater OS in patients treated with FOLFIRINOX. 13 , 14 Recently, the first results of NALIRIFOX versus GEM-NAB, presented during ASCO congress, reported OS in favor of NALIRIFOX. 15 These data are opposed to other phase III recent trial, stopped for futility, showing a signal in favor of GEM-NAB over FOLFIRINOX regimen.…”

Section: Introductionmentioning

confidence: 99%

French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel versus gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients

Demaziere,

Mourgues,

Lambert

et al. 2024

Ther Adv Med Oncol

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Context: In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions. Objectives: GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB versus gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients. Design: All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened. Methods: This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals. Results: The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38–0.77, p = 0.001), with a median OS of 6.2 months ( versus 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration. Conclusion: The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.

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Enhanced Glutaminolysis Drives Hypoxia-Induced Chemoresistance in Pancreatic Cancer

et al. 2023

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Pancreatic ductal adenocarcinoma (PDAC) exhibits severe hypoxia, which is associated with chemoresistance and worse patient outcome. It has been reported that hypoxia induces metabolic reprogramming in cancer cells. However, it is not well known whether metabolic reprogramming contributes to hypoxia. Here, we established that increased glutamine catabolism is a fundamental mechanism inducing hypoxia, and thus chemoresistance, in PDAC cells. An extracellular matrix (ECM) component-based in vitro 3D cell printing model with patient-derived PDAC cells that recapitulates the hypoxic status in PDAC tumors showed that chemoresistant PDAC cells exhibit markedly enhanced glutamine catabolism compared to chemoresponsive PDAC cells. The augmented glutamine metabolic flux increased the oxygen consumption rate via mitochondrial oxidative phosphorylation (OXPHOS), promoting hypoxia and hypoxia-induced chemoresistance. Targeting glutaminolysis relieved hypoxia and improved chemotherapy efficacy in vitro and in vivo. This work suggests that targeting the glutaminolysis–OXPHOS–hypoxia axis is a novel therapeutic target for treating patients with chemoresistant PDAC.

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Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System

Cited by 3 publications

References 24 publications

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data

French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel versus gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients

Enhanced Glutaminolysis Drives Hypoxia-Induced Chemoresistance in Pancreatic Cancer

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