A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study

Otsuka, Taiga; Shirakawa, Tsuyoshi; Shimokawa, Mototsugu; Koga, Futa; Kawaguchi, Yasunori; Ueda, Yujiro; Nakazawa, Junichi; Komori, Azusa; Otsu, Satoshi; Arima, Shiho; Fukahori, Masaru; Okabe, Yoshinobu; Makiyama, Akitaka; Taguchi, Hiroki; Honda, Takeshi; Shibuki, Taro; Nio, Kenta; Ide, Yasushi; Mizuta, Toshihiko; Mitsudo, Kenji; Ureshino, Norio

doi:10.1007/s10147-021-01859-2

Cited by 21 publications

(22 citation statements)

References 30 publications

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“…A different toxicity spectrum for the two schedules is well-known. The higher gastrointestinal toxicity of FFX is consistent with other reports [ 19 , 25 , 28 ], and a higher rate of anemia with GN has also been shown [ 25 ]. On the other hand, higher rates of febrile neutropenia are usually reported with FFX [ 12 , 20 , 22 , 25 ], but the use of granulocyte colony-stimulating factors (G-CSF), that is very heterogeneous among different centers, should be considered.…”

Section: Discussionsupporting

confidence: 91%

“…On the other hand, higher rates of febrile neutropenia are usually reported with FFX [ 12 , 20 , 22 , 25 ], but the use of granulocyte colony-stimulating factors (G-CSF), that is very heterogeneous among different centers, should be considered. As for peripheral neuropathy, higher rates are often reported with GN [ 22 , 25 , 28 ], but we have only reported grade 3/4 events; moreover, the assessment of peripheral neuropathy, specifically concerning grade 2 or 3 events, is based on self-reported functional impairment, thus some inconsistencies cannot be ruled out.…”

Section: Discussionmentioning

confidence: 86%

“…This bias is common when treating metastatic PC patients in real-world: several studies have shown a different treatment allocation based on patient’s age and PS. More specifically, younger age and better PS are associated with an increased use of FFX [ 10 , 11 , 13 , 27 , 28 ], while more comorbidities are associated with an increased use of GN [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Given the above considerations (different inclusion criteria from trials, population imbalance between treatments), more reliable data come from studies that take into account these differences and perform an appropriate matching of cohorts. A propensity score-adjusted analysis did not report any difference, neither in OS nor in PFS, in 255 patients with metastatic disease, while showed a different toxicity spectrum [ 28 ]. On the other hand, in a series of 216 patients with metastatic disease where a higher survival was reported with FFX, the application of a comparative propensity score analysis (based on age, gender, PS, and presence of liver metastases), showed only a trend toward greater OS with FFX [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

et al. 2021

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FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81–1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82–1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

et al. 2021

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“…Despite advances in surgical techniques, radiation, and chemotherapy, the 5-year survival rate is one of the lowest at just 10% (2). Current therapeutic options for advanced disease include fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel, however these therapies are limited by a generally short duration of response and cumulative toxicities (3,4). Activation of the DNA damage response (DDR) pathway in cancer cells with chemotherapy can lead to treatment resistance (5).…”

Section: Introductionmentioning

confidence: 99%

WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA damaging therapies commonly used in PDAC treatment. The purpose of this study was to identify combination partners for AZD1775, including standard chemotherapy or targeted agents, in PDAC preclinical models. Low powered preliminary screens demonstrated that two of the four PDX models responded better to the combinations of AZD1775 with irinotecan or capecitabine than to either single agent. Following the screens, two full powered PDAC PDX models of differing p53 status were tested with the combinations of AZD1775 and irinotecan or capecitabine. The combinations of AZD1775 and SN38 or 5-FU were also tested on PDAC cell lines. Cellular proliferation was measured using an IncuCyte Live Cell Imager and apoptosis was measured using a Caspase-Glo 3/7 assay. Flow cytometry was conducted to measure alterations in cell cycle distribution. Western blot analysis was used to determine the effects of the drug combinations on downstream effectors. In PDX models with mutated p53 status, there was significant tumor growth inhibition from the combination of AZD1775 with irinotecan or capecitabine (P ≤ 0.03), while PDX models with wild type p53 did not show anti-tumor synergy from the same combinations (P ≥ 0.08). The combination of AZD1775 with SN38 or 5-FU significantly decreased proliferation in all PDAC cell lines, and enhanced apoptosis in multiple cell lines. Cell cycle distribution was disrupted from the combination of AZD1775 with SN38 or 5-FU which was recorded as G2M arrest and decreased G1 phase. AZD1775 inhibited phospho-CDC2 and increased the expression of γH2AX that was either maintained or enhanced after combination with SN38 or 5-FU. The combination of AZD1775 with irinotecan/SN38 or capecitabine/5-FU showed anti-tumor effects in vivo and in vitro in PDAC models. These results support further investigation for these combination strategies to enhance outcomes for PDAC patients.

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Analysis of the cost‐effectiveness of proton beam therapy for unresectable pancreatic cancer in Japan

Hiroshima,

Kondo,

Sawada

et al. 2023

Cancer Medicine

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BackgroundProton beam therapy (PBT) has recently been included in Japan's social health insurance benefits package. This study aimed to determine the cost‐effectiveness of PBT for unresectable, locally advanced pancreatic cancer (LAPC) as a replacement for conventional photon radiotherapy (RT).MethodsWe estimated the incremental cost‐effectiveness ratio (ICER) of PBT as a replacement for three‐dimensional conformal RT (3DCRT), a conventional photon RT, using clinical evidence in the literature and expense complemented by expert opinions. We used a decision tree and an economic and Markov model to illustrate the disease courses followed by LAPC patients. Effectiveness was estimated as quality‐adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as the costs. The stability of the ICER against the assumptions made was appraised using sensitivity analyses.ResultsThe effectiveness of PBT and 3DCRT was 1.67610615 and 0.97181271 QALY, respectively. The ICER was estimated to be ¥5,376,915 (US$46,756) per QALY. According to the suggested threshold for anti‐cancer therapy from the Japanese authority of ¥7,500,000 (US$65,217) per QALY gain, such a replacement would be considered cost‐effective. The one‐way and probabilistic sensitivity analyses demonstrated stability of the base‐case ICER.ConclusionPBT, as a replacement for conventional photon radiotherapy, is cost‐effective and justifiable as an efficient use of finite healthcare resources. Making it a standard treatment option and available to every patient in Japan is socially acceptable from the perspective of health economics.

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A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study

Cited by 21 publications

References 30 publications

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma

Analysis of the cost‐effectiveness of proton beam therapy for unresectable pancreatic cancer in Japan

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