Sex Is an Independent Prognostic Indicator for Survival and Relapse/Progression-Free Survival in Metastasized Stage III to IV Melanoma: A Pooled Analysis of Five European Organisation for Research and Treatment of Cancer Randomized Controlled Trials

2013 ◽  
Vol 31 (18) ◽  
pp. 2337-2346 ◽  
Author(s):  
Arjen Joosse ◽  
Sandra Collette ◽  
Stefan Suciu ◽  
Tamar Nijsten ◽  
Poulam M. Patel ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Metastatic Tumor ◽  
Stage Iii ◽  
Controlled Trials ◽  
Free Survival ◽  
European Organisation ◽  
Randomized Controlled ◽  
Female Advantage

Purpose To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature. Patients and Methods Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively. Results In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load. Conclusion The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.

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 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.

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 Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials

Blood ◽  
2020 ◽  
Vol 136 (9) ◽  
pp. 1091-1104 ◽  
Author(s):  
Charlotte A. Bradbury ◽  
Zoe Craig ◽  
Gordon Cook ◽  
Charlotte Pawlyn ◽  
David A. Cairns ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Controlled Trials ◽  
Phase 3 ◽  
Free Survival ◽  
Randomized Controlled ◽  
Before And After ◽  
Prospective Cohorts ◽  
Prevention Guidelines

Abstract Newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulatory drugs are at high risk of venous thromboembolism (VTE), but data are lacking from large prospective cohorts. We present thrombosis outcome data from Myeloma IX (n = 1936) and Myeloma XI (n = 4358) phase 3 randomized controlled trials for NDMM that treated transplant-eligible and transplant-ineligible patients before and after publication of thrombosis prevention guidelines. In Myeloma IX, transplant-eligible patients randomly assigned to cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) induction had higher risk of VTE compared with patients treated with cyclophosphamide, thalidomide, and dexamethasone (CTD) (22.5% [n = 121 of 538] vs 16.1% [n = 89 of 554]; adjusted hazard ratio [aHR],1.46; 95% confidence interval [95% CI], 1.11-1.93). For transplant-ineligible patients, those randomly assigned to attenuated CTD (CTDa) induction had a higher risk of VTE compared with those treated with melphalan and prednisolone (MP) (16.0% [n = 68 of 425] vs 4.1% [n = 17 of 419]; aHR, 4.25; 95% CI, 2.50-7.20). In Myeloma XI, there was no difference in risk of VTE (12.2% [n = 124 of 1014] vs 13.2% [n = 133 of 1008]; aHR, 0.92; 95% CI, 0.72-1.18) or arterial thrombosis (1.2% [n = 12 of 1014] vs 1.5% [n = 15 of 1008]; aHR, 0.80; 95% CI, 0.37-1.70) between transplant-eligible pathways for patients treated with cyclophosphamide, lenalidomide, and dexamethasone (CRD) or CTD. For transplant-ineligible patients, there was no difference in VTEs between attenuated CRD (CRDa) and CTDa (10.4% [n = 95 of 916] vs 10.7% [n = 97 of 910]; aHR, 0.97; 95% CI, 0.73-1.29). However, arterial risk was higher with CRDa than with CTDa (3.1% [n = 28 of 916] vs 1.6% [n = 15 of 910]; aHR, 1.91; 95% CI, 1.02-3.57). Thrombotic events occurred almost entirely within 6 months of treatment initiation. Thrombosis was not associated with inferior progression-free survival (PFS) or overall survival (OS), apart from inferior OS for patients with arterial events (aHR, 1.53; 95% CI, 1.12-2.08) in Myeloma XI. The Myeloma XI trial protocol incorporated International Myeloma Working Group (IMWG) thrombosis prevention recommendations and compared with Myeloma IX, more patients received thromboprophylaxis (80.5% vs 22.3%) with lower rates of VTE for identical regimens (CTD, 13.2% vs 16.1%; CTDa, 10.7% vs 16.0%). However, thrombosis remained frequent in spite of IMWG-guided thromboprophylaxis, suggesting that new approaches are needed.

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 &gt;70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (&gt;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 &gt;70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin &lt;12 g/dL, ECOG PS ≥2, and elevated β2-microglobulin. Median follow-up was 5.6 years. Patients &gt;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 &gt;70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P &lt; .001). Age &gt;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 &gt;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.

Postoperative adjuvant therapy with tamoxifen, tegafur-uracil (UFT), or both in women with node-negative breast cancer: A pooled analysis of six randomized controlled trials (relapse-free survival data)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
S. Nakamura ◽  
O. Abe
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Randomized Controlled Trials ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Randomized Controlled ◽  
Node Negative Breast Cancer

633 Background: In Japan, 6 randomized controlled trials of the oral 5-fluorouracil derivative tegafur-uracil (UFT) and tamoxifen (TAM), given alone or in combination, have been simultaneously performed in women with node-negative breast cancer. We performed a pooled analysis, based on the intention to treat, of individual patient data from these 6 trials (involving 2934 patients). Data on overall survival, the primary endpoint, have been reported previously (Noguchi et al., Journal of Clinical Oncology, 2005). We now report data on relapse-free survival (median follow-up, 6.2 years). Methods: Three 3-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT) and three 4-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT vs. surgery plus TAM and UFT) were performed in women with node-negative breast cancer. The results underwent a pooled analysis. Results: The 5-year relapse-free survival rate was 87.9% with surgery alone (n = 860; risk ratio [RR], 1), 90.5% with surgery plus TAM (n = 865; RR, 0.81; confidential interval [CI], 0.60–1.11; P = 0.21), 89.9% with surgery plus UFT (n = 860; RR, 0.83; CI, 0.66–1.21; P = 0.46), and 92.7% with surgery plus UFT and TAM (n = 349; RR, 0.63; CI, 0.39–0.99; P = 0.046). Subset analysis showed that combination therapy with UFT and TAM was not effective for women with estrogen-receptor-negative breast cancer (RR, 0.90; CI, 0.46–1.75; P = 0.75), but was very effective for women with estrogen-receptor-positive breast cancer (RR, 0.39; CI, 0.19–0.79; P = 0.009). Conclusions: Our results suggest that the effectiveness of oral fluoropyrimidine derivatives is enhanced by concurrent treatment with TAM in women with node-negative breast cancer. This contrasts with the results of previous studies showing that the response to anthracycline-based chemotherapy is attenuated in patients concurrently receiving TAM. No significant financial relationships to disclose.

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