NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors

Wang‐Gillam, Andrea; Hubner, Richard A; Siveke, Jens T.; Hoff, Daniel D. Von; Belanger, Bruce; Jong, Floris A. de; Mirakhur, Beloo; Chen, Li Tzong

doi:10.1016/j.ejca.2018.12.007

Cited by 198 publications

(169 citation statements)

References 21 publications

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“…The modified FOLFIRINOX regimen consisted of oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , irinotecan 150 mg/m 2 , and continuous fluorouracil 2400 mg/m 2 , without bolus fluorouracil. However, mFOLFIRINOX remains a protocol with many side effects, so it could be administered especially to fit patients [22,23], since in the adjuvant setting there are no serological alterations (such as an increase in bilirubin) which may affect the use of irinotecan [24]. Certainly, the choice of adjuvant treatment can also affect the choice of first-line treatment, since the appearance of oxaliplatin neuropathy makes it difficult to subsequently use a combination with nab-paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Galvano

Castiglia

Rizzo

et al. 2020

Cancers

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Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52–0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50–0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03–1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.

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Section: Discussionmentioning

confidence: 99%

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Galvano

Castiglia

Rizzo

et al. 2020

Cancers

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“…In 2015, the FDA approved Onivyde (liposomal irinotecan) for the use in metastatic pancreatic cancer, a disease with a dismal prognosis for affected patients. The phase 3 trial showed an (albeit moderate) extension of overall survival (Wang-Gillam et al, 2016) that was confirmed in a recent follow-up study (Wang-Gillam et al, 2019). In 2017, Vyxeos (liposomal synergistic combination of daunorubicin and cytarabin) was approved for acute myeloid leukemia (Lancet et al, 2018).…”

Section: Introductionmentioning

confidence: 87%

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

Thomas

Weber

2019

Front. Bioeng. Biotechnol.

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The exploitation of nanosized materials for the delivery of therapeutic agents is already a clinical reality and still holds unrealized potential for the treatment of a variety of diseases. This review discusses physiological barriers a nanocarrier must overcome in order to reach its target, with an emphasis on cancer nanomedicine. Stages of delivery include residence in the blood stream, passive accumulation by virtue of the enhanced permeability and retention effect, diffusion within the tumor lesion, cellular uptake, and arrival at the site of action. We also briefly outline strategies for engineering nanoparticles to more efficiently overcome these challenges: Increasing circulation half-life by shielding with hydrophilic polymers, such as PEG, the limitations of PEG and potential alternatives, targeting and controlled activation approaches. Future developments in these areas will allow us to harness the full potential of nanomedicine.

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“…A subgroup analysis showed that the benefit was maintained in patients that had received 5-FU but not in those previously treated with irinotecan. A recent update of this trial showed an estimated 1-year survival of 26% for nanoliposomal irinotecan plus 5-FU combination versus 16% for 5 FU alone [40].…”

Section: Second-line Systemic Therapy For Metastatic or Local Advancementioning

confidence: 99%

Current Systemic Treatment Options for Metastatic and Unresectable Pancreatic Cancer

Caglevic¹,

Mahave²,

Sanhueza³

et al. 2021

Challenges in Pancreatic Cancer

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Metastatic and local advanced unresectable pancreatic cancers are lethal conditions that always carry a poor prognosis with rare exceptions. Currently, the mainstay of therapy is cytotoxic chemotherapy plus best supportive care. First-line therapy for patients with a good performance status includes FOLFIRINOX or gemcitabine plus nab-paclitaxel regimens. Patients carrying a deleterious germline BRCA mutation can be treated with maintenance olaparib after FOLFIRINOX. Patients with a poor performance status, but still fit enough for chemotherapy, may be treated with single agent gemcitabine. Second-line therapy will depend on previous therapy and current performance status. Options for patients treated with gemcitabine-based regimens are 5-fluorouracil plus leucovorin plus either nanoliposomal irinotecan, irinotecan or oxaliplatin. Patients that were treated with first line FOLFIRINOX may benefit from a gemcitabine-based chemotherapy, but evidence from randomized trials is lacking. Other options like immunotherapy and targeted therapies yield benefit only in very selected cases, and it is still an area of research.

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NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors

Cited by 198 publications

References 21 publications

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

Current Systemic Treatment Options for Metastatic and Unresectable Pancreatic Cancer

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