Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis

Pusceddu, Sara; Ghidini, Michele; Torchio, Martina; Corti, Francesca; Tomasello, Gianluca; Niger, Monica; Prinzi, Natalie; Nichetti, Federico; Coinu, Andrea; Bartolomeo, Maria Di; Cabiddu, Mary; Passalacqua, Rodolfo; Braud, Filippo de; Petrelli, Fausto

doi:10.3390/cancers11040484

Cited by 89 publications

(87 citation statements)

References 34 publications

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“…Although our analysis is limited to discuss the overall outcomes of 1L nab-P+ GEM, because we included only 2L population, current findings may indicate that subsequent 2L and 3L chemotherapy may prolong the survival of patients with mPDAC who started 1L nab-P+GEM. Although there is no head-to-head comparative trial, FOLFIRINOX showed numerically better survival outcomes compared to nab-P+GEM in 1L setting [2,3], recent retrospective analyses and meta-analysis in realworld setting have revealed that survival outcomes with these regimens may be similar in mPDAC patients [4,20]. The efficacy of subsequent 2L and 3L chemotherapy after progression on 1L nab-P+GEM shown in our study may contribute to these results.…”

Section: Discussionsupporting

confidence: 48%

Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

et al. 2020

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Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM. Materials and Methods Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors. Results Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy. Conclusion 2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

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Section: Discussionsupporting

confidence: 48%

Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

et al. 2020

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“…Based on 16 retrospective studies that included 2123 gemcitabine plus nab-paclitaxel treated patients and 1690 FOLFIRINOX treated patients, no statistical significantly differences were found in terms of overall risk of death, PFS and RR. Toxicity was in line of the pivotal trials [36]. These results may help to conclude that despite of the numerically superiority in OS of the phase 3 FOLFIRINOX trial when it is compared with MPACT trial, and in the absence of a comparative head to head phase 3 trial for these 2 regimens, clinicians may use any of those according with their experience but also taking account of the medical conditions and biography of each patient to be treated.…”

Section: : Current First-line Options For the Treatment Of Metastmentioning

confidence: 60%

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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“…Thus, the therapeutic bene ts of FOLFIRINOX were better than GEM-NAB in this cohort. However, previous meta-analysis based on 16 retrospective studies from Italy reported that the survival outcomes were similar between FOLFIRINOX and GEM-NAB [44], with HR for PFS of 0.88 (95% CI 0.71-1.1, p = 0.26) and HR for OS of 0.99 (95% CI 0.84-1.16, p = 0.9). In our meta-analysis, the treatment e cacy was also similar between FOLFIRINOX and GEM-NAB, which was same with previous studies.…”

Section: Discussionmentioning

confidence: 89%

“…Modi ed FOLFIRINOX and GEM-NAB are the most frequently used rst-line treatments for advanced PC. Previous studies have conducted e cacy comparisons between modi ed FOLFIRINOX and FOLFIRINOX [9] or between GEM-NAB and FOLFIRINOX [44], and the outcomes were similar in these comparisons. However, until now, relative effects of modi ed FOLFIRINOX and GEM-NAB treatments are unknown as no direct comparisons have been conducted.…”

Section: Discussionmentioning

confidence: 93%

Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

Chen

Hua

Wang

et al. 2020

Preprint

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Background: Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC) at present. Due to the lack of direct comparison, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. Methods: The eligible retrospective studies of treatments related to modified FOLFIRINOX and GEM-NAB were searched up to 4 April 2020. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study.Results: Twenty-two studies including 6351 patients were involved in this network meta-analysis. The comparisons based on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy. But GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 0.70; 95% CI: 0.51-0.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. Conclusions: Based on current evidence, modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity comparisons. Many factors should be considered for the optimal treatment formulation and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

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Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis

Cited by 89 publications

References 34 publications

Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Current Systemic Treatment Options for Metastatic and Unresectable Pancreatic Cancer

Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

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