scholarly journals Advanced melanoma, a pharmacological evaluation

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Anabela Andrade ◽  
Jorge Balteiro
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Advanced Melanoma ◽  
New Drugs ◽  
High Rate ◽  
Free Survival ◽  
Dismal Prognosis

Abstract Background Cutaneous melanoma is an aggressive cancer that occurs in melanocytes, located in the epidermis. Historically it has a high rate of morbidity and mortality, due to the resistance and toxicity of traditional therapies. Its incidence has increased annually by 4% to 8%. Until 2011 it was still considered a devastating and almost always fatal disease in a few months. Advances in therapies have significantly improved the results of most patients with advanced melanoma, especially those with a BRAFV600 mutation, which account for almost 50% of tumors. Before the recent evolution in treatment, the prognosis and overall survival were considered very bad. The introduction of new drugs has improved progression-free survival and overall survival, as well as producing faster clinical responses. Methods Comparison of endpoints such as progression-free survival and overall melanoma survival from the Summary of Product Characteristics (SPC) studies of each drug in the therapeutic groups under assessment used in the disease. The variables used were the Endpoints Global Survival at various times (12 months, 24 months, 36 months and the median) and Progression-Free Survival. Results Combined immunotherapy (Nivolumab and Ipilimumab) improves overall survival and progression-free survival, achieving better results than targeted therapy. In this, the combination of a BRAF inhibitor and a MEK inhibitor, presents better results with the combination of Encorafenib and Binimetinib. Conclusions Both targeted therapy and immunotherapy transform melanoma with a dismal prognosis into a life-threatening illness.

Clinical outcomes of postoperative intraperitoneal chemotherapy for patients with early-stage high-grade serous ovarian cancer (HGSC) treated at British Columbia cancer agency.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17105-e17105
Author(s):  
Joohyun Lee ◽  
Anna Tinker
Keyword(s):  
Ovarian Cancer ◽  
British Columbia ◽  
Overall Survival ◽  
Clinical Outcomes ◽  
Early Stage ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Stage I ◽  
High Rate ◽  
Free Survival

e17105 Background: Intraperitoneal (IP) chemotherapy has been shown to prolong overall survival in optimally debulked stage III ovarian cancer in randomized trials. In British Columbia, we extrapolated this benefit of IP chemotherapy to early stage HGSC patients for the last 10 years, as these patients are optimally debulked at surgery but still have a high rate of recurrence. We conducted a retrospective study of clinical outcomes associated with IP/IV chemotherapy compared to IV chemotherapy for optimally debulked stage I HGSC cases. Methods: This was a retrospective cohort study of women with stages IA-IC HGSC who had primary surgery between 2007-2015, and received either IV or IP/IV chemotherapy post-operatively. We compared progression-free survival (PFS) and overall survival (OS) outcomes between these 2 groups. Kaplan-Meier method evaluated chemotherapy delivery route with progression free survival (PFS) and overall survival (OS), using the statistical program R. Results: We identified 99 patients; 80 (81%) received IV chemotherapy and 19 (19%) received IP/IV chemotherapy. Among IP/IV cohort, 2/19 (11%) discontinued IP therapy during treatment due to abdominal pain at IP port site or hypersensitivity reaction to IV paclitaxel. 5-year PFS was 88.4% (74.5-100%) and 69.7% (58.7-82.7%) among the IP/IV and IV cohorts, respectively (p = 0.549). There was a trend for higher 5-year OS for the IP/IV group; however, this did not reach statistical significance (100% vs. 71.4%; p = 0.182). Conclusions: In our study, IP/IV chemotherapy for stage I HGSC patients was associated with a trend for higher 5-year PFS and OS compared to IV chemotherapy. This observation warrants further prospective investigation.

scholarly journals Progression-Free Survival and Overall Survival Among a Patient Cohort of Relapsed/Refractory Mycosis Fungoides in France, Germany, Italy, Spain and the United Kingdom

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5879-5879
Author(s):  
Martine Bagot ◽  
Timothy Illidge ◽  
Nicola Pimpinelli ◽  
Mehul Dalal ◽  
Athanasios Zomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Mycosis Fungoides ◽  
Systemic Therapy ◽  
Research Funding ◽  
Index Date ◽  
Progression Free Survival ◽  
High Rate ◽  
Advisory Committees ◽  
Free Survival

Background and Aim: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL) wherein those with advanced stage have a poor prognosis. The objective of this study was to describe clinical characteristics and survival in MF patients who were refractory or had relapsed after a first systemic therapy. Methods: A retrospective chart review study was conducted at 27 sites in Europe. Patients enrolled had a diagnosis of MF and proved to be relapsed/refractory (R/R) prior to 1-Jan-2016 after a first systemic therapy. Overall survival (OS) and progression-free survival (PFS) were estimated from the date of R/R event (defined as the index date) using Kaplan-Meier estimates. PFS was defined as death, progression, second relapse or refractory, or presence of subsequent treatment after index date. Results: This study included 104 advanced R/R MF patients with a median age of 54.5 years (range: 21-82). The median follow-up was 3.5 years (range: 0-20.7) after index date. In total 80% of patients experienced a second R/R, with a median time to second R/R of 15.8 months (range: 0.6-174.6). The median age at death was 65 years (range: 42-85). In total 39 deaths (37.5%) were observed. Among those patients who had a known cause of death (N=35), 18 died of CTCL progression, 11 of CTCL complication or drug toxicity and 7 of other causes. The estimated median OS was 11.5 years (95% CI: 6.5 - not reached). The median PFS was 1.3 years (95% CI: 1.0-2.1). Conclusions: The high rate of R/R and low PFS suggest that the clinical burden of R/R MF is significant in five European countries, and recently approved targeted therapies have the potential of improving outcomes. Disclosures Bagot: Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Illidge:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics, Inc.: Research Funding; Div of Cancer Sciences, Faculty of Biology, Medicine and Health, Univ of Manchester, National Institutes of Health and Research Biomedical Research Center, Manchester Academic Health Sciences, Christie Hospital National Health Service Foundation Trust: Employment. Dalal:Takeda: Employment. Zomas:Takeda: Employment. Trinchese:Takeda: Employment. Little:Takeda: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Ortiz-Romero:Actelion: Consultancy, Membership on an entity's Board of Directors or advisory committees; 4SC: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; miRagen: Membership on an entity's Board of Directors or advisory committees; PLCG1: Patents & Royalties; Kyowa: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; MEDA: Research Funding.

scholarly journals Focus on the dabrafenib, vemurafenib, and trametinib in clinical outcome of melanoma: a systematic review and meta-analysis

2020 ◽  
Vol 3 (2) ◽  
Author(s):  
Ida Ayu Widya Anjani ◽  
Anak Agung Bagus Putra Indrakusuma ◽  
I Gede Krisna Arim Sadeva ◽  
Putri Ayu Wulandari ◽  
Luh Made Mas Rusyati ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Clinical Outcome ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Good Prognosis ◽  
Braf Gene ◽  
Free Survival ◽  
Review Manager ◽  
Ottawa Scale

Background: Melanoma is the most serious lethal skin cancer, affects the melanin producer cells (melanocytes). Surgery is the most common treatment, whereas for the advance stage the development of a treatment is recommended. BRAF (Dabrafenib and Vemurafenib) inhibitor or MEK inhibitor (Trametinib) is used as the most frequently targeted therapy of melanoma due to more than 80% patient with positive BRAF mutation. In this review, those treatments will be investigated systematically to identify their clinical outcome.Method: This systematic literature review (SLR) was performed from Cochrane, Science Direct, Google Scholar, and Pubmed. Cochrane Risk-of-Bias Tool RoB2 is used to assess RCT studies and New-castle Ottawa Scale Assessment to assess cohort studies by 3 different assessors. Data analysis was carried out by using Review Manager (RevMan 5.4). Heterogenicity test was assessed by I2  and Chi2 statisticResult: There are 20 studies used in this article (13 RCT and 7 cohorts). The overall survival (OS) and progression-free survival (PFS) of study that using targeted therapy (vemurafenib, trametinib, or dabrafenib) compare other therapies (chemotherapy, immunotherapy,etc) showed risk ratio (RR) was 1.12 (95%CI 1.07,1.17;  I2=100%; p<0,00001). The OS and PFS with monotherapy compare of vemurafenib, trametinib, or dabrafenib with combination therapy showed RR was 1.09 (95%CI.06,1.13;I2=99%; p<0,00001). Conclusion: BRAF and MEK targeted therapy has a good prognosis for a patient with a positive BRAF gene mutation and could be combined with other therapy for a better clinical outcome rather than monotherapy.Keyword: melanoma, dabrafenib, vemurafenib, and trametinib

scholarly journals Analysis of BRAF and NRAS mutation status in advanced melanoma patients treated with anti-CTLA-4 antibodies: Association with overall survival?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9025-9025 ◽  
Author(s):  
Joanna Mangana ◽  
Simone M. Goldinger ◽  
Katja Schindler ◽  
Sima Rozati ◽  
Anna L. Frauchiger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Advanced Melanoma ◽  
Braf V600e ◽  
Wild Type ◽  
Nras Mutation ◽  
Mutation Status ◽  
Mutational Status ◽  
Melanoma Patients

9025 Background: Ipilimumab and tremelimumab are human monoclonal antibodies against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival with durable-long-term responses for advanced melanoma patients both in first-and second-line setting. Up to date, there is no proven association between the BRAF-V600E mutation and the disease control rate (DCR) in response to Ipilimumab. Moreover, significantly shorter survival rates have been reported in patients harboring an NRAS mutation than in those without. This retrospective analysis was carried out to assess if BRAF (V600) and NRAS mutation status affects the clinical outcome of Ipilimumab-treated melanoma patients. Methods: This is a retrospective multi-center analysisof 71 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The cut-off for the estimation of overall survival was end of November 2012. Results: The median overall survival of BRAFV600/NRAS mutant patients (n=44) was 1,41 years compared with 2.67 years in BRAF/NRAS wild-type patients (n=27). Although this difference was not statistically significant there was a trend for improved survival in wild-type patients. Of the 71 patients analyzed, 56 received chemotherapy prior to Ipilimumab. In the BRAF/NRAS mutant cohort, 12 patients received Ipilimumab following either a BRAF- or a MEK- inhibitor. Of those 12 patients, 8 progressed and were unable to complete Ipilimumab. Of the 4 patients who completed 4 cycles of Ipilimumab, 2 were subsequently treated with a BRAF inhibitor. Furthermore out of the 71 patients, 8 patients received a BRAF or a MEK inhibitor after progression; 5 of them are still alive. Conclusions: This is the first retrospective study to evaluate the association of both BRAF and NRAS mutational status with the overall survival of Ipilimumab-treated patients. There was a trend towards an improved survival in the BRAF/NRAS wild-type subpopulation. Additional patients will be examined to foster these preliminary results.

Efficacy of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6023-6023 ◽  
Author(s):  
Vivek Subbiah ◽  
Robert J. Kreitman ◽  
Zev A. Wainberg ◽  
Jae Yong Cho ◽  
Jan H.M. Schellens ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Treatment Options ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Open Label ◽  
Dismal Prognosis

6023 Background: ATC is a rare, aggressive malignancy with a dismal prognosis. Median overall survival (OS) is < 6 mo. Combined BRAF and MEK inhibition is efficacious in BRAF V600–mutated melanoma and lung cancer. One-fourth of ATCs harbor activating BRAF V600E mutations; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated ATC. Methods: In this phase 2, open-label trial (NCT02034110), pts with BRAF V600E mutations in 9 rare tumor types, including ATC, received continuous D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer with no standard-of-care treatment options. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), OS, and safety. We report data from the ATC cohort. Results: 16 pts with BRAF V600E–mutated ATC had evaluable data with a median follow-up time of 47 wk (range 4-120 wk). BRAF V600E mutations were centrally confirmed in 15/16 pts. Median age was 72 y; all 16 pts had undergone prior tumor radiation and/or surgery and 6/16 pts (38%) had received ≥1 prior line of systemic therapy. Investigator-assessed confirmed ORR was 69% (11/16; 95% CI, 41%-89%), with 7/11 responses ongoing at the time of data cut. The Bayesian estimate of ORR was 69% (95% credible interval, 47%-87%) with a 100% probability that this ORR exceeded the 15% historical RR. Median DOR, PFS, and OS were not estimable due to insufficient progression and death events. Kaplan-Meier estimates of DOR, PFS, and OS at 12 mo were 90%, 79%, and 80%, respectively. The safety population comprised 100 pts enrolled in 7/9 histologies. Among all pts, 92% had an AE. Common AEs of any grade for all histologies were fatigue (38%), pyrexia (37%), and nausea (35%). In the ATC cohort, the most common grade 3/4 events were hyponatremia (19%), pneumonia (13%), and anemia (13%). Conclusions: D+T combination therapy significantly improved outcomes in ATC with a favorable safety profile. This regimen represents a clinically meaningful therapeutic advance for pts with advanced/metastatic BRAF V600–mutated ATC. Clinical trial information: NCT02034110.

Innovative approach to determine overall survival (OS) benefit for orphan diseases using case match control analyses (CMCA): The PROPEL experience of pralatrexate in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7521-7521
Author(s):  
Owen A. O'Connor
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Complete Response ◽  
Original Data ◽  
New Drugs ◽  
Orphan Diseases ◽  
Free Survival ◽  
Randomized Studies ◽  
Significant Difference ◽  
Two Populations

7521 Background: The challenges in conducting randomized studies in orphan diseases poses limitations on our ability to identify the most promising treatments. Randomized studies in this setting can take protracted periods of time to complete, can be very expensive while not offering the promise of significant commercial return, and could become irrelevant as the pace of scientific advancement continues. The majority of drugs approved in this setting are often approved on surrogate end-points like progression free survival (PFS) or complete response (CR) rates in single arm studies. CMCA are statistically stronger than single arm studies, and can be highly informative in this setting. Methods: We established an integrated international database of patients with R/R PTCL to clarify the OS advantage of pralatrexate using original data from the PROPEL study, an international, multicenter phase II study in patients with R/R PTCL. The propensity score was used to match cases and controls. Cases were matched based on histology, number of previous treatments received, age at diagnosis and sex. Results: With 1:1 ratio match, we identified 83 cases and 83 controls. In total, 83 patients out of 109 treated on the PROPEL study were successfully matched. OS was plotted for each of the two study populations. The survival curves for the control population were found to be nearly identical to that reported for this population from other datasets. The overall survival was 4.04 months (95% CI 2.83, 5.78), which is consistent with historical controls describing this population. The median OS in for the pralatrexate treated cohort in this analysis was 16.6 months (95% CI: 11.99-25.56). The OS was a highly statistically significant difference between these two populations, with a hazard ratio of 0.426 (95% CI: 0.296-0/61). This difference held up for each of the major histologic subsets, including PTCL-NO and angioimmunoblastic PTCL. Conclusions: This approach can be used to better understand how new drugs in orphan diseases perform in heterogeneous patient populations. Clinical trial information: NCT00364923.

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