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

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiayuan Chen ◽  
Qingling Hua ◽  
Haihong Wang ◽  
Dejun Zhang ◽  
Lei Zhao ◽  
...  

Abstract Background Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. Methods The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. 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 were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78–1.63; PFS: HR: 1.19; 95% CI: 0.85–1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04–1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. Conclusions The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

2020 ◽  
Author(s):  
Jiayuan Chen ◽  
Qingling Hua ◽  
Haihong Wang ◽  
Dejun Zhang ◽  
Lei Zhao ◽  
...  

Abstract 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.


Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1746 ◽  
Author(s):  
Kun-I Lin ◽  
Jia-Lian Yang ◽  
Yu-Chao Lin ◽  
Che-Yi Chou ◽  
Jin-Hua Chen ◽  
...  

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).


2009 ◽  
Vol 27 (33) ◽  
pp. 5513-5518 ◽  
Author(s):  
David Cunningham ◽  
Ian Chau ◽  
Deborah D. Stocken ◽  
Juan W. Valle ◽  
David Smith ◽  
...  

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.


2019 ◽  
Vol 11 ◽  
pp. 175883591986190 ◽  
Author(s):  
Giandomenico Roviello ◽  
Silvia Paola Corona ◽  
Gabriella Nesi ◽  
Enrico Mini

Background: The aim of this study was to perform a literature-based meta-analysis to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in first-line metastatic renal cell carcinoma (RCC), focusing on the predictive role of PD-L1 expression. Methods: The primary outcome was overall survival, and secondary outcomes were progression-free survival (PFS) and objective response. We planned a subgroup analysis for overall survival according to PD-L1 status. Results: Five studies were included in the analysis for a total of 4063 cases. Overall survival was greater in PD-L1 positive tumours (HR = 0.49, 95% CI: 0.36–0.67; p < 0.001). The pooled analysis of the unselected cases showed a statistically significative improvement in PFS with the use of ICIs (HR = 0.85, 95% CI: 0.72–0.99; p = 0.04) and we found a greater PFS benefit (HR = 0.65, 95% CI: 0.57–0.74; p < 0.001) in patients with PD-L1 positive tumours. Conclusions: This study supports the efficacy of ICIs and, although a significant clinical benefit has been reported in PD-L1 negative patients, a greater efficacy of ICIs was observed in PD-L1 positive patients. More prospective randomized studies are needed to clarify the role of PDL-1 status in metastatic RCC treated with ICIs.


2019 ◽  
Vol 11 ◽  
pp. 175883591985036 ◽  
Author(s):  
Elena Gabriela Chiorean ◽  
Winson Y. Cheung ◽  
Guido Giordano ◽  
George Kim ◽  
Salah-Eddin Al-Batran

Background: No clinical trial has directly compared nab-paclitaxel/gemcitabine (nab-P/G) with FOLFIRINOX (fluorouracil/leucovorin/oxaliplatin/irinotecan) in metastatic or advanced pancreatic cancer (mPC or aPC). We conducted a systematic review of real-world studies comparing these regimens in the first-line setting. Methods: Embase and MEDLINE databases through 22 January 2019, and Gastrointestinal Cancers Symposium 2019 abstracts were searched for real-world, retrospective studies comparing first-line nab-P/G versus FOLFIRINOX in mPC or aPC that met specific parameters. Studies with radiotherapy were excluded. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Of 818 records initially identified, 35 were duplicates and 749 did not meet the eligibility criteria, mostly because they were either not comparative ( n = 356) or not first line ( n = 245). The remaining 34 studies (21 mPC; 13 aPC) assessed >6915 patients who received nab-P/G or FOLFIRINOX. In the studies identified, the median overall survival (OS) reached 14.4 and 15.9 months with nab-P/G and FOLFIRINOX, respectively, and median progression-free survival reached 8.5 and 11.7 months, respectively. Safety data were reported in 14 studies (2205 patients), including 8 single-institutional studies. In most single-institutional studies that reported safety data, rates were higher with FOLFIRINOX versus nab-P/G for grade 3/4 neutropenia (five of six studies) and febrile neutropenia (all three studies), while rates of grade 3/4 peripheral neuropathy were higher with nab-P/G in four of seven studies. Conclusions: Although FOLFIRINOX was associated with slightly longer median OS in more studies, the differences, when available, were not statistically significant. Therefore, a randomized, controlled trial is warranted. Toxicity profile differences represent key considerations for treatment decisions.


2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.


2020 ◽  
Vol 12 ◽  
pp. 175883592090540 ◽  
Author(s):  
Victor H. F. de Jesus ◽  
Marcos P. G. Camandaroba ◽  
Vinicius F. Calsavara ◽  
Rachel P. Riechelmann

Background: There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity. Methods: We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions. Results: Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel. Conclusions: Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).


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