Comparative efficacy and safety of dabrafenib in combination with trametinib versus competing adjuvant therapies for high-risk melanoma

2019 ◽  
Vol 8 (16) ◽  
pp. 1349-1363 ◽  
Author(s):  
Rohini Sharma ◽  
Roy Koruth ◽  
Steve Kanters ◽  
Eric Druyts ◽  
Ahmad Tarhini
Keyword(s):  
High Risk ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Distant Metastasis ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Comparable Efficacy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival

Aim To conduct a systematic literature review of high-risk resectable cutaneous melanoma adjuvant therapeutics and compare safety and efficacy. Methods: The systematic literature review included randomized controlled trials investigating: dabrafenib plus trametinib (DAB + TRAM), nivolumab, pembrolizumab, ipilimumab, vemurafenib, chemotherapy and interferons. Outcomes included overall survival (OS), relapse-free survival, distant metastasis-free survival and safety. All outcomes were synthesized using Bayesian network meta-analysis. Results: Across relapse-free survival, distant metastasis-free survival and OS, DAB + TRAM had the lowest estimated hazards of respective events relative to all other treatments (exception relative to nivolumab in OS). Differences were significant relative to placebo, chemotherapy, interferons and ipilimumab. Conclusion: DAB + TRAM has improved efficacy over historical treatment options (ipilimumab, interferons and chemotherapy) and comparable efficacy with other targeted and immune checkpoint inhibitors.

scholarly journals Myasthenia Gravis Is Not an Independent Prognostic Factor of Thymoma: Results of a Propensity Score Matching Trial of 470 Patients

2020 ◽  
Vol 10 ◽  
Author(s):  
Yirui Zhai ◽  
Yong Wei ◽  
Zhouguang Hui ◽  
Yushun Gao ◽  
Yang Luo ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Distant Metastasis ◽  
Progression Free Survival ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival ◽  
Matching Trial ◽  
Pathological Subtypes

ObjectiveThe association between the prognosis of thymoma and MG remains controversial. Differences in clinical characteristics and treatments between patients with and without MG may affect the findings of those studies. We designed this propensity score matching trial to investigate whether MG is an independent prognostic predictor in thymoma.MethodsPatients with pathologically diagnosed thymoma and MG were enrolled in the MG group. Moreover, the propensity score matching method was used to select patients who were diagnosed with thymoma without MG from the database of two participating centers. Matched factors included sex, age, Masaoka stage, pathological subtypes, and treatments. Matched patients were enrolled in the non-MG group. Chi-squared test was used to compare the characteristics of the two groups. Overall survival, local-regional relapse-free survival, distant metastasis-free survival, progression-free survival, and cancer-specific survival were calculated from the diagnosis of thymoma using the Kaplan–Meier method.ResultsBetween April 1992 and October 2018, 235 patients each were enrolled in the MG and non-MG groups (1:1 ratio). The median ages of patients in the MG and non-MG groups were 46 years old. The World Health Organization pathological subtypes were well balanced between the two groups (B2 + B3: MG vs. non-MG group, 63.0 vs. 63.4%, p = 0.924). Most patients in both groups had Masaoka stages I–III (MG vs. non-MG group, 90.2 vs. 91.5%, p = 0.631). R0 resections were performed in 86.8 and 90.2% of the MG and non-MG groups, respectively (p = 0.247). The median follow-up time of the two groups was 70.00 months (MG vs. non-MG group, 73.63 months vs. 68.00 months). Five-year overall survivals were 92.5 and 90.3%, 8-year overall survivals were 84.2 and 84.2%, and 10-year overall survivals were 80.2 and 81.4% (p = 0.632) in the MG and non-MG groups, respectively. No differences were found in the progression-free survival, distant metastasis-free survival, and local-regional relapse-free survival between the two groups.ConclusionMG is not an independent or direct prognostic factor of thymoma, although it might be helpful in diagnosis thymoma at an early stage, leading indirectly to better prognosis.

scholarly journals Clinical Study of Nasopharyngeal Carcinoma Treated by Helical Tomotherapy in China: 5-Year Outcomes

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lei Du ◽  
Xin-Xin Zhang ◽  
Lin Ma ◽  
Lin-Chun Feng ◽  
Fang Li ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Distant Metastasis ◽  
Helical Tomotherapy ◽  
Antibody Therapy ◽  
Monoclonal Antibody Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival

Background.To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT).Methods.Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy.Results.Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3–38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS.Conclusions.Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

scholarly journals Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kabirraaj Toor ◽  
Mark R. Middleton ◽  
Keith Chan ◽  
Adenike Amadi ◽  
Andriy Moshyk ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Efficacy And Safety ◽  
Effective Treatment Option ◽  
Free Survival ◽  
Risk Of Recurrence

Abstract Background Immune checkpoint inhibitors and targeted therapies are approved for adjuvant treatment of patients with resected melanoma; however, they have not been compared in randomized controlled trials (RCTs). We compared the efficacy and safety of adjuvant nivolumab with other approved treatments using available evidence from RCTs in a Bayesian network meta-analysis (NMA). Methods A systematic literature review was conducted through May 2019 to identify relevant RCTs evaluating approved adjuvant treatments. Outcomes of interest included recurrence-free survival (RFS)/disease-free survival (DFS), distant metastasis-free survival (DMFS), all-cause grade 3/4 adverse events (AEs), discontinuations, and discontinuations due to AEs. Time-to-event outcomes (RFS/DFS and DMFS) were analyzed both assuming that hazard ratios (HRs) are constant over time and that they vary. Results Of 26 identified RCTs, 19 were included in the NMA following a feasibility assessment. Based on HRs for RFS/DFS, the risk of recurrence with nivolumab was similar to that of pembrolizumab and lower than that of ipilimumab 3 mg/kg, ipilimumab 10 mg/kg, or interferon. Risk of recurrence with nivolumab was similar to that of dabrafenib plus trametinib at 12 months, however, was lower beyond 12 months (HR [95% credible interval] at 24 months, 0.46 [0.27–0.78]; at 36 months, 0.28 [0.14–0.59]). Based on HRs for DMFS, the risk of developing distant metastases was lower with nivolumab than with ipilimumab 10 mg/kg or interferon and was similar to dabrafenib plus trametinib. Conclusion Adjuvant therapy with nivolumab provides an effective treatment option with a promising risk–benefit profile.

Prognostic Significance of Radiologic Extranodal Extension in Nasopharyngeal Cancer

2021 ◽  
pp. 019459982110088
Author(s):  
Melek Karakurt Eryılmaz ◽  
Cengiz Kadıyoran
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Distant Metastasis ◽  
Prognostic Significance ◽  
Nasopharyngeal Cancer ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Extranodal Extension ◽  
Distant Metastasis Free Survival

Objective The aim of the present study was to evaluate the prognostic value of radiologic extranodal extension (rENE) in patients with nasopharyngeal cancer. Study Design Retrospective review. Setting Tertiary university hospital. Methods We identified patients with nasopharyngeal cancer and lymph node metastasis who underwent pretreatment neck computed tomography or magnetic resonance imaging and evaluated rENE from the involved lymph node. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to compare rENE+ and rENE– groups for local regional relapse–free survival, distant metastasis–free survival, and overall survival. Results Of 61 cases, 24 (39.3%) were rENE+ and 37 (60.7%) were rENE–. The median follow-up was 65.5 months. The 5-year distant metastasis–free survival and overall survival rates were lower in the rENE+ group than the rENE– group (70.8% vs 89.2%, P = .016; 66.7% vs 89.2%, P = .01, respectively). Differences in locoregional control between the groups were not significant ( P = .18). The 5-year rates for local regional relapse–free survival were 87.5% for rENE+ and 91.9% for rENE–. In multivariate analysis, the presence of rENE was a significant independent adverse prognostic factor for distant metastasis–free survival and overall survival. Conclusions We showed that rENE is an independent prognostic factor for poor distant control and survival in patients with nasopharyngeal cancer.

scholarly journals Diffusion-weighted MRI for predicting treatment response in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min Kyoung Lee ◽  
Yangsean Choi ◽  
So-Lyung Jung
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Treatment Response ◽  
Distant Metastasis ◽  
Meta Analysis ◽  
Local Relapse ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival ◽  
Hazard Ratios

AbstractEarly prediction of treatment response in nasopharyngeal carcinoma is clinically relevant for optimizing treatment strategies. This meta-analysis was performed to evaluate whether apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can predict treatment response of patients with nasopharyngeal carcinoma. A systematic search of PubMed-MEDLINE and Embase was performed to identify relevant original articles until July 22, 2021. We included studies which performed DWI for predicting locoregional treatment response in nasopharyngeal carcinoma treated with neoadjuvant chemotherapy, definitive chemoradiation, or radiation therapy. Hazard ratios were meta-analytically pooled using a random-effects model for the pooled estimates of overall survival, local relapse-free survival, distant metastasis-free survival and their 95% CIs. ADC showed a pooled sensitivity of 87% (95% CI 72–94%) and specificity of 70% (95% CI 56–80%) for predicting treatment response. Significant between-study heterogeneity was observed for both pooled sensitivity (I2 = 68.5%) and specificity (I2 = 92.2%) (P < 0.01). The pooled hazard ratios of low pretreatment ADC for assessing overall survival, local relapse-free survival, and distant metastasis-free survival were 1.42 (95% CI 1.09–1.85), 2.31 (95% CI 1.42–3.74), and 1.35 (95% CI 1.05–1.74), respectively. In patients with nasopharyngeal carcinoma, pretreatment ADC demonstrated good predictive performance for treatment response.

Intermittent High-Dose Intravenous Interferon Alfa-2b for Adjuvant Treatment of Stage III Melanoma: Final Analysis of a Randomized Phase III Dermatologic Cooperative Oncology Group Trial

2015 ◽  
Vol 33 (34) ◽  
pp. 4077-4084 ◽  
Author(s):  
Peter Mohr ◽  
Axel Hauschild ◽  
Uwe Trefzer ◽  
Alexander Enk ◽  
Wolfgang Tilgen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Adjuvant Treatment ◽  
Distant Metastasis ◽  
Interferon Alfa ◽  
Stage Iii ◽  
High Dose ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival

Purpose To evaluate the efficacy, safety, tolerability, and quality of life (QoL) in patients receiving intravenous, intermittent high-dose interferon alfa-2b (IFN-α-2b [iHDI]) compared with standard high-dose IFN-α-2b (HDI). Patient and Methods Patients with stage III resected lymph node or in-transit metastasis from cutaneous malignant melanoma were randomly assigned to receive either a standard HDI regimen or three courses of IFN-α-2b 20 MIU/m2 administered intravenously 5 days a week for 4 weeks then repeated every 4 months. Distant metastasis-free survival was the primary end point for efficacy analysis. In addition, relapse-free survival, overall survival, safety as determined by Common Terminology Criteria for Adverse Events criteria, and QoL were secondary end points. Results Of 649 patients enrolled, 22 patients were excluded from the intent-to-treat analysis. The remaining 627 patients were well balanced between the arms according to sex, age, and stage. After a median follow-up of 55 months, a multivariable Cox model revealed no significant differences for distant metastasis-free survival (hazard ratio [HR], 1.21; P = .12) or overall survival (HR, 1.01; P = .85). In contrast, the difference for relapse-free survival was significant (HR, 1.27; P = .03), favoring standard HDI. Early termination of treatment because of adverse events or QoL occurred significantly more often with HDI than with iHDI (26.0% v 14.8%; P < .001). Conclusion Although the safety and QoL profiles for the intermittent regimen were favorable, no significant difference was observed for survival while the HR for relapse with iHDI was increased. Therefore, an iHDI regimen, as tested here, cannot be recommended as adjuvant treatment for high-risk melanoma.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

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