Efficacy of frontline treatment regimens in follicular lymphoma: A network meta-analysis of phase III randomized controlled trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7556-7556
Author(s):  
Yucai Wang ◽  
Shouhao Zhou ◽  
Fang Yang ◽  
Grzegorz S. Nowakowski ◽  
Thomas Matthew Habermann ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Pairwise Comparison ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Trials ◽  
Treatment Regimens ◽  
Randomized Controlled ◽  
Frontline Treatment

7556 Background: The frontline treatment for advanced follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a network meta-analysis of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Methods: Data were extracted from 7 RCTs (FOLL05, StiL NHL1, BRIGHT, PRIMA, GALLIUM, StiL NHL7, and RELEVANCE). Progression-free survival (PFS) was compared between 11 regimens with different immunochemotherapy and maintenance strategies. To incorporate direct and indirect comparisons, random-effects Bayesian network meta-analyses were conducted after adjusting for study-wise variation. The posterior inference was derived based on Markov chain Monte Carlo methods and implemented using JAGS v4.3.0. Pairwise comparison of hazard ratios (HRs) and 95% credible intervals (CIs) were calculated. Results: PFS HRs of other regimens compared to the reference regimen are summarized in the Table. Compared to Rituximab(R)-Benda, R-CHOP had inferior PFS, R-CHOP-R, G-CHOP-G, and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. Compared to R-CHOP-R, G-CHOP-G and R-Len-R had similar PFS, while R-Benda-R, R-Benda-R4 and G-Benda-G had better PFS. In addition, the PFS for G-Benda-G was similar to R-Benda-R4 (HR 0.94, 95% CI 0.78-1.09) but better than R-Benda-R (HR 0.82, 95% CI 0.75-0.97). Conclusions: Compared with the commonly used R-Benda and R-CHOP-R regimens, G-CHOP-G, R-Benda-R and R-Benda-R4 had better PFS, while the chemotherapy-free regimen R-Len-R had similar PFS. [Table: see text]

scholarly journals Efficacy of front-line immunochemotherapy for follicular lymphoma: a network meta-analysis of randomized controlled trials

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Yucai Wang ◽  
Shouhao Zhou ◽  
Xinyue Qi ◽  
Fang Yang ◽  
Matthew J. Maurer ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Controlled Trials ◽  
Front Line ◽  
Free Survival ◽  
Randomized Controlled

Abstract Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.

scholarly journals Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 358
Author(s):  
Claudio Ricci ◽  
Giuseppe Lamberti ◽  
Carlo Ingaldi ◽  
Cristina Mosconi ◽  
Nico Pagano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neuroendocrine Neoplasms ◽  
Controlled Trials ◽  
Endocrine Tumors ◽  
Randomized Controlled ◽  
Grade 3

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP–NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3–4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate.

scholarly journals Outcomes of older patients with follicular lymphoma using individual data from 5922 patients in 18 randomized controlled trials

2021 ◽  
Vol 5 (6) ◽  
pp. 1737-1745
Author(s):  
Carla Casulo ◽  
Jesse G. Dixon ◽  
Fang-Shu Ou ◽  
Eva Hoster ◽  
Bruce A. Peterson ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Follicular Lymphoma ◽  
Randomized Controlled Trials ◽  
Age Groups ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Early Disease ◽  
End Points ◽  
Randomized Controlled ◽  
Disease Outcomes

Abstract Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years). Primary end points were early disease outcomes, CR24 and CR30, and progression-free survival (PFS) at 24 months (PFS24). Secondary end points were PFS and overall survival (OS). We identified 5922 previously untreated FL patients from 18 RCTs. Patients age >70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin <12 g/dL, ECOG PS ≥2, and elevated β2-microglobulin. Median follow-up was 5.6 years. Patients >70 years did not differ from patients ≤70 years in rates of CR24, CR30, or PFS24. With a median OS of 14.6 years for all patients, median OS was 7.4 and 15.7 years for patients >70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P < .001). Age >70 years was a significant predictor of OS and PFS due to higher rates of death without progression, but not PFS24, CR24, or CR30. FL patients >70 years treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs.

Efficacy of Hypo-Methylating Agents in the Treatment of Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3632-3632
Author(s):  
Ambuj Kumar ◽  
Alan F. List ◽  
Rahul Mhaskar ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Supportive Care ◽  
Randomized Controlled Trials ◽  
Confidence Intervals ◽  
Meta Analysis ◽  
Phase Iii ◽  
P Value ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Methylating Agents

Abstract Background: With the FDA approval of two hypomethylating agents (HA) for the treatment of myelodysplastic syndromes (MDS), both azacitidine (AZA-C) and decitabine have shown widespread usage. These agents improved response rates (RR) in phase III registration trials, however, overall survival (OS) was not significantly improved. Furthermore, head to head comparison of AZA-C versus decitabine is lacking. We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of AZA-C and decitabine versus supportive care (SC), and AZA-C versus decitabine for the treatment of MDS. Methods: A comprehensive literature search of MEDLINE, EMBASE and Cochrane library database was undertaken to identify all phase III randomized controlled trials (RCT) published through July 2008. Meetings abstracts from ASCO, ASH and European Society for Hematology were searched for the years 2006–2007. Data extraction and meta-analysis on benefits and harms of HA for MDS was performed as per the methods recommended by the Cochrane Collaboration. Indirect comparison of AZA-C versus decitabine was conducted according to the methods developed by Bucher et al and Glenny et al and were extended to calculate hazard ratios (HR). We created the following chain of inference: we first pooled RCTs that compared AZA-C with SC, and decitabine versus SC. We then compared the pooled estimates to obtain the unbiased estimate in treatment differences between decitabine and AZA-C. Results: We found 4 RCTs assessing the efficacy of HA for the treatment of MDS. Two RCTs compared AZA-C versus SC, and 2 compared decitabine versus SC. The results from 1 trial describing the effects of decitabine versus SC were reported as a press release stating that OS was not significant between two arms, however, data were not available for this analysis. The results for all comparisons are summarized in the table below. Meta-analysis of RCTs comparing HA versus SC showed significantly better OS, EFS, and RR in favor of HA without a significant increase in treatment-related mortality (TRM). Comparison of AZA-C versus SC also showed significantly better OS, EFS and RR favoring AZA-C without significant risk of TRM. In one RCT comparing decitabine versus SC, RR was significantly superior in the decitabine arm. However, there was no difference in OS, EFS and TRM between decitabine and SC. Evaluation of decitabine versus AZA-C showed significantly better OS and RR favoring AZA-C, whereas EFS and TRM were similar. Conclusion: This first systematic review on the efficacy of HA versus SC shows that OS, EFS and RR are superior with HA without significant TRM. Additionally, use of AZA-C is associated with significantly improved OS and RR compared to decitabine. In order to definitively confirm these findings, a prospective RCT comparing AZA-C and decitabine is warranted. Results from this systematic review on the efficacy of AZA-C and decitabine should be considered the threshold against which efficacy of future agents in MDS should be tested. Outcome Comparisons Hypo-methylating agents versus supportive care (3 RCTs; N=719) Conclusion Azacitidine versus supportive care (2 RCTs; N= 549) Conclusion Decitabine versus supportive care (1 RCT; N=170) Conclusion Azacitadine versus Decitabine (Indirect comparison) Conclusion Overall Survival Hazard ratio (HR)(95% Confidence Intervals) P-value HR=0.79 (0.67, 0.95) p=0.01 Hypo- methylating agents better HR=0.62 (0.48, 0.78) p=0.00 Azacitidine better HR=1.064 (0.82, 1.38) p=0.636 No difference HR=0.579 (0.41, 0.82) p=0.002 Azacitidine better Event-free survival Hazard ratio (HR) (95% Confidence Intervals) P-value HR=0.59 (0.46, 0.75) p=0.00 Hypo- methylating agents better HR=0.58 (0.44, 0.76) p=0.00 Azacitidine better HR=0.64 (0.35, 1.19) p=0.16 No difference HR=0.89 (0.46, 1.80) p=0.753 No difference Response rate Risk ratio (RR) (95% Confidence Intervals) P-value RR=1.28 (1.19, 1.37) p=0.00 Hypo- methylating agents better RR=1.37 (1.25, 1.52) p=0.00 Azacitidine better RR=1.2 (1.08, 1.31) p=0.00 Decitabine better RR=1.15 (1.0, 1.314) p=0.05 Azacitidine better Treatment-related mortality Risk ratio (RR) (95% Confidence Intervals) P-value RR=0.69 (0.36, 1.32) p=0.264 No difference RR=2.79 (0.12, 67.64) p=0.528 No difference RR=0.65 (0.34, 1.26) p=0.203 No difference RR=4.29 (0.16, 111.1) p=0.381 No difference

Maintenance Therapies for Multiple Myeloma (MM): A Network Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 236-236
Author(s):  
Helen Mahony ◽  
Ambuj Kumar ◽  
Rahul Mhaskar ◽  
Branko Miladinovic ◽  
Keith Wheatley ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Phase Iii ◽  
Novel Agents ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
American Society ◽  
Novel Agent

Abstract Abstract 236 Background: There is little consensus on which maintenance therapy clinicians should choose for their patients. Since 1999, the three novel agents of bortezomib, lenalidomide, and thalidomide have been approved for use among patients with MM. These agents have been increasingly used as maintenance therapy. To date, only two randomized controlled trials of maintenance therapy have examined the efficacy of these novel agents head-to-head. Here, we conduct a network meta-analysis of bortezomib, lenalidomide, and thalidomide to determine which of these novel agents could potentially increase overall survival (OS) and progression-free survival (PFS). Methods: A comprehensive literature search of MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and meetings abstracts from American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology and European Hematology Association was undertaken to identify all phase III randomized controlled trials (RCTs) of maintenance therapy published until July 2012. We applied the Bayesian mixed treatment comparison (MTC) method under the random-effects model. The indirect comparisons were constructed from trials that have one treatment in common. For each included RCT, we calculated the hazard ratio (HR) and its corresponding standard error and used this to calculate the indirect estimates of HR and corresponding credible intervals (CrI). We also ranked the treatments according to the probability of best treatment and calculated the surface underneath the cumulative ranking curve (SUCRA). All analyses were conducted in WinBUGS 1.4.3 and Stata 11.2. Results: The network, number of trials for each comparison, and number of patients enrolled is shown in Figure 1. The network for OS was based on 12 RCTs enrolling 5542 patients and the network for PFS was constructed from 13 RCTs and 5784 patients. The MTC networks were consistent for both OS and PFS. For both OS and PFS, two comparisons were produced (Figure 2). For OS, the analysis showed that none of the treatments were superior. For PFS, lenalidomide was superior to thalidomide (HR = 0.58, 95% CrI [0.37, 0.94]). The estimates of SUCRA and rank probabilities (Figure 3) suggested that for OS bortezomib was best followed by lenalidomide and thalidomide. For PFS, lenalidomide was best followed by bortezomib and thalidomide. Conclusion: Using the MTC method, we found no evidence that any of the novel agents are superior to one another in terms of OS. Lenalidomide was the only novel agent which was superior to another active therapy (thalidomide). While these results provide preliminary evidence to which novel agent may be more beneficial as maintenance therapy, definitive conclusions cannot be reached until large, well designed RCTs evaluating these therapies head-to-head are conducted. Disclosures: No relevant conflicts of interest to declare.

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