scholarly journals Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis

2018 ◽  
Vol 10 ◽  
pp. 175883591878850 ◽  
Author(s):  
Katrin M. Sjoquist ◽  
Sarah J. Lord ◽  
Michael L. Friedlander ◽  
Robert John Simes ◽  
Ian C. Marschner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Controlled Trials ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
The Difference

Background: Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. Methods: In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Results: Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest ( r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2 = 0.66; platinum/paclitaxel, r2 = 0.44; triplet combinations, r2 = 0.22; biologicals, r2 = 0.30. The median PPS increased over time for the experimental ( Ptrend = 0.03) and control arms ( Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS ( r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger ( r2 = 0.64) than where the median PPS was longer ( r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies.

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.

Ibrutinib for Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: A Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5596-5596
Author(s):  
Shijia Zhang ◽  
Larysa Sanchez ◽  
Jieqi Liu ◽  
Victor Chang ◽  
Stuart L. Goldberg
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Controlled Trials ◽  
Small Lymphocytic Lymphoma ◽  
Bulky Disease ◽  
Free Survival ◽  
Randomized Controlled

Background: Ibrutinib, a Bruton's tyrosine kinase inhibitor, was approved by FDA for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This study aims to evaluate the efficacy and safety data from randomized controlled trials (RCT) of ibrutinib-based therapy in patients with CLL or SLL. Methods: PubMed, ASH, and ASCO databases (2008-2016) were searched for randomized control trials of ibrutinib therapy (either single-agent or combination) for chronic lymphocytic leukemia or small lymphocytic lymphoma through June 30, 2016. Study endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AE). Pooled hazard ratios (HR) for survival outcomes and relative risks (RR) for dichotomous data with 95% confidence interval (CI) were calculated with a random effect model using MedCalc. Results: Four randomized controlled trials (RESONATE-1, RESONATE-2, HELIOS, and CLL12) were identified, but CLL12 trial was excluded from this study since the efficacy data were not available at the time of this meta-analysis. Pooled data from the 3 RCTs (1238 patients) showed that ibrutinib-based therapy improved overall survival (HR 0.419; 95% CI 0.242-0.725, P = 0.002) and progression-free survival (HR 0.201; 95% CI 0.162-0.251, P < 0.001) compared to regimens without ibrutinib. Subgroup analysis showed that the PFS benefits were independent of sex (male: HR 0.188, 95% CI 0.143-0.249, P < 0.001; female: HR 0.225, 95% CI 0.154-0.331, P < 0.001), Rai stage (0-II: HR 0.154, 95% CI 0.109-0.217, P < 0.001; III-IV: HR 0.235, 95% CI 0.167-0.333, P < 0.001), bulky disease (<5 cm: HR 0.219, 95% CI 0.155-0.309, P < 0.001; ≥5 cm: HR 0.179, 95% CI 0.135-0.238, P < 0.001) or chromosome 11q deletion (positive: HR 0.099, 95% CI 0.060-0.163, P < 0.001; negative: HR 0.261, 95% CI 0.212-0.322, P < 0.001). Ibrutinib-based therapy significantly increased the risk of developing all-grade diarrhea (RR = 2.135, 95% CI = 1.437-3.174, p < 0.001), pyrexia (RR = 1.265, 95% CI = 1.011-1.583, p = 0.040), and arthralgia (RR = 1.863, 95% CI = 1.101-3.152, p = 0.020), but not anemia (RR = 0.955, 95% CI = 0.694-1.313, p = 0.777), neutropenia (RR = 1.048, 95% CI = 0.760-1.446, p = 0.774), fatigue (RR = 0.897, 95% CI = 0.746-1.078, p = 0.247), or nausea (RR = 0.951, 95% CI = 0.600-1.506, p = 0.829). Conclusions: Ibrutinib-based therapy significantly improves OS and PFS (independent of sex, Rai stage, bulky disease or chromosome 11q deletion) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, but increases the risks of all-grade adverse events including diarrhea, pyrexia, and arthralgia. Disclosures Chang: Johnson and Johnson: Other: Stock; Amgen: Other: Research; Boehringer Ingelheim: Other: Research. Goldberg:Neostem: Equity Ownership; Bristol Myers Squibb, Novartis: Speakers Bureau; COTA Inc: Employment; Pfizer: Honoraria; Novartis: Consultancy.

scholarly journals Different Chemotherapy Regimens in the Management of Advanced or Metastatic Urothelial Cancer: a Bayesian Network Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 50 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Yi Wang ◽  
Lingyan Xu ◽  
Xianghu Meng ◽  
Zhiqiang Qin ◽  
Yamin Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Urothelial Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Controlled Trials ◽  
First Line ◽  
Randomized Controlled ◽  
Metastatic Urothelial Cancer

Background/Aims: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has achieved remarkable progresses in therapeutic paradigm, particularly in the advanced/metastatic stages. However, both clinicians and patients are confused when it comes to choosing the optimal chemotherapy. Hence, this article was aimed to conduct a comprehensive comparison of different chemotherapy regimens for advanced or metastatic UC in terms of survival benefits or adverse events. Methods: The online databases PubMed, EMBASE and Web of Science were searched systematically and comprehensively for randomized controlled trials (RCTs) up to September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The effectiveness and safety of included regimens were conducted to provide a hierarchy by means of rank probabilities with the help of “R-3.4.0” software and the “gemtc-0.8.2” package. The surface under the cumulative ranking curve (SUCRA) was also incorporated in our analysis for ranking the corresponding chemotherapy regimens. Results: Ten different chemotherapy regimens involved in this article were predominantly of trials in a first-line setting, and eight clinical outcomes were ultimately analyzed in this study. In terms of Overall response rate (ORR), Overall survival (OS) or Progression-free survival (PFS)/Time to progression (TTP), the rank probabilities and SUCRA indicated that Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first-line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP, GC+sorafenib also displayed its superiority in comparison with GC or MVAC. Despite their survival benefits, PCG or GC+sorafenib presented a relatively higher incidence of adverse events. Conclusion: Our results revealed that by adding a paclitaxel or sorafenib into the first-line GC, it could yield a better survival benefit, but also worsen adverse events for advanced/ metastatic UC. Clinically, physicians should weigh the merits of these approaches to maximize the survival benefits of eligible patients.

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