A Bayesian Meta-Analysis of Multiple Treatment Comparisons of Systemic Regimens for Advanced Pancreatic Cancer

Chan, Kelvin K.; Shah, Keya; Lien, Kelly; Coyle, Doug; Lam, Henry; Ko, Yoo‐Joung

doi:10.1371/journal.pone.0108749

Cited by 40 publications

(27 citation statements)

References 32 publications

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“…This overall response rate (ORR) compares favorably with that reported historically across a number of studies in patients treated with Gem alone (7%-13%). A recent Bayesian meta-analysis comparing nine treatment regimens suggested that FOLFIRINOX provided the best treatment response for advanced PDA (21). The FOLFIRINOX regimen achieved a 32% ORR in metastatic PDA; however, it was accompanied by a high toxicity rate, effectively limiting its use to patients with excellent performance status (5).…”

Section: Discussionmentioning

confidence: 99%

Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer

Hingorani

Harris

Beck

et al. 2016

Clinical Cancer Research

290

205

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Purpose: This phase Ib study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a phase II dose for patients with untreated stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated.Experimental Design: Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3þ3 dose-escalation design. In cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre-and post-PEGPH20 administration. Several safety parameters were evaluated.Results: Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n ¼ 4), 1.6 (n ¼ 4), or 3.0 mg/kg (n ¼ 20), respectively. The most common PEGPH20-related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression-free survival (PFS) and overall survival (OS) rates were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pretreatment tissue hyaluronan (HA) levels, median PFS and OS rates were 7.2 and 13

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Section: Discussionmentioning

confidence: 99%

Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer

Hingorani

Harris

Beck

et al. 2016

Clinical Cancer Research

290

205

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“…A recent indirect comparison study found that FFX was associated with improved OS compared to nab -P + G, and had a comparable safety profile, suggesting FFX as the more cost-effective option for 1L therapy [14]. A Bayesian mixed treatment comparison similarly found an 83% probability that FFX was the best regimen versus 11% for nab -P + G, with OS hazard ratio (HR) favoring FFX versus nab -P + G (although not statistically significant), and no obvious difference in toxicities [15]. Another recent indirect comparison of the efficacy and safety of these two regimens found, however, that the OS for nab -P + G was larger than that of FFX, although the survival benefit was not statistically significant [16].…”

Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States

et al. 2018

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Introductionnab-Paclitaxel plus gemcitabine (nab-P + G) and FOLFIRINOX (FFX) are among the most common first-line (1L) therapies for metastatic adenocarcinoma of the pancreas (MPAC), but real-world data on their comparative effectiveness are limited.MethodsThis retrospective cohort study compared the efficacy and safety of 1L nab-P + G versus FFX, overall and under specific treatment sequences. Medical records were reviewed by 215 US physicians who provided information on MPAC patients who initiated 1L therapy with nab-P + G or FFX between April 1, 2015 and December 31, 2015. Study outcomes were overall survival (OS) and tolerability. OS was compared using Kaplan–Meier curves and adjusted Cox proportional hazards models.ResultsIn total, 654 medical records were reviewed, including those of 337 and 317 patients initiated on nab-P + G and FFX as 1L MPAC therapy, respectively. nab-P + G-initiated patients were older, less likely to have ECOG ≤ 1, and had more comorbidities than FFX-initiated patients. Median OS (mOS) was 12.1 and 13.8 months for nab-P + G- and FFX-initiated patients, respectively (HR = 0.99, P = 0.96). Among patients with ECOG ≤ 1, mOS was 14.1 and 13.7 months, respectively (HR = 1.00, P = 0.99). Among patients with 1L nab-P + G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of 16.3 and 16.6 months, respectively (HR = 1.04, P = 0.76). The rates of diarrhea, fatigue, mucositis, and nausea and vomiting were significantly higher in the FFX than nab-P + G cohort.ConclusionThe real-world survival was similar between patients receiving 1L nab-P + G or FFX both overall and among patients who received active 2L treatments. In addition, nab-P + G was associated with significantly lower rates of common AEs compared with FFX.FundingCelgene.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0784-z) contains supplementary material, which is available to authorized users.

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“…Indirect comparisons using the ESMO magnitude of clinical benefit scale show a higher score for the FOLFIRINOX regimen when compared to GNP (5/5 vs 2/5, with a higher score indicating a better regimen in terms of survival benefit and quality of life)[14]. In addition, a Bayesian meta-analysis comparing multiple systemic protocols in advanced pancreatic cancer showed a trend toward better survival with FOLFIRINOX compared to GNP[15]. In view of this debate, we conducted this review to discuss the main comparison points between FOLFIRINOX and GNP, including the design of the two pivotal trials, toxicity profiles, quality of life, real life experiences, choice of second-line therapy and cost effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

Ghosn¹,

Ibrahim²,

Assi³

et al. 2016

WJG

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Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness.

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A Bayesian Meta-Analysis of Multiple Treatment Comparisons of Systemic Regimens for Advanced Pancreatic Cancer

Cited by 40 publications

References 32 publications

Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer

Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer

Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States

Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

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