scholarly journals Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1994 ◽  
Author(s):  
Alessandro A. E. Testori ◽  
Silvia Chiellino ◽  
Alexander C.J. van Akkooi
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Adjuvant Therapy ◽  
Target Therapy ◽  
Survival Rates ◽  
Immune Checkpoint Blockade ◽  
Severe Toxicity ◽  
Toxic Side Effect ◽  
The Past ◽  
Melanoma Patients

This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years—anti-PD-1 or BRAF-directed therapy is the new standard of care.

EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi91-vi91
Author(s):  
Yeonju Kim ◽  
Terri Armstrong ◽  
Mark Gilbert ◽  
Orieta Celiku
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Tumor ◽  
Objective Response ◽  
Survival Rates ◽  
Maximum Tolerated Dose ◽  
Secondary Outcome ◽  
Patient Reported

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.

scholarly journals The management of Hodgkin lymphoma in adolescents and young adults: burden of disease or burden of choice?

Blood ◽  
2018 ◽  
Vol 132 (4) ◽  
pp. 376-384 ◽  
Author(s):  
Jamie E. Flerlage ◽  
Monika L. Metzger ◽  
Nickhill Bhakta
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Young Adults ◽  
Hodgkin Lymphoma ◽  
Burden Of Disease ◽  
Health Care Services ◽  
Survival Rates ◽  
Adolescents And Young Adults ◽  
Adult Health ◽  
Treatment Regimens

Abstract Adolescents and young adults (AYAs) comprise the largest age group affected by Hodgkin lymphoma (HL). Despite excellent overall survival of AYA patients with HL due to advances in treatment regimens, therapy-associated late effects continue to be a concern in HL survivors, especially for younger patients who have decades of life remaining. Since the first clinical trial for HL with chemotherapy in 1964, subsequent protocols have attempted to reduce chemotherapy-induced toxicities and yet maintain high overall survival rates. Today, new analytic methods applied to data from survivorship cohorts, such as the recently described cumulative burden of disease metric, can be used to inform changes for future protocols. Although pediatric and adult trial consortia have followed this process, the AYA population, an age cohort split between pediatric and adult health care services, faces many barriers to care and is the least likely to be enrolled in clinical trials. AYA patients with HL theoretically have a choice to be treated in pediatric or adult protocols when presented with these options. Recent efforts by the National Clinical Trials Network, the Children’s Oncology Group, and others have been made to ensure that the burden of choice for the AYA population is not greater than the burden of disease.

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival over Five Decades

2016 ◽  
Vol 82 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Daniel D. Kirchoff ◽  
Gary B. Deutsch ◽  
Leland J. Foshag ◽  
Ji Hey Lee ◽  
Myung-Shin Sim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Mucosal Melanoma ◽  
Surgical Interventions ◽  
Entire Cohort ◽  
The Past ◽  
Survival Difference ◽  
Disease Site ◽  
The Ideal

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neo-adjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

The current role of systemic therapy in the management of Malignant Melanoma of the skin: a literature review

2004 ◽  
Vol 4 (4) ◽  
pp. 161-175 ◽  
Author(s):  
Elizabeth Reeves ◽  
P. Bridge ◽  
R. M. Appleyard
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Survival Rates ◽  
Success Rates ◽  
Systemic Treatments ◽  
Melanoma Patients ◽  
Disease Free

Melanoma patients can be split into two main categories that have different aims for treatment; localised disease with either intermediate or high-risk of recurrence after surgery, and metastatic disease. Over the past decade, there have been many clinical trials looking at improving the success rates for localised and metastatic melanoma with alternative systemic treatments, namely immunotherapy, biochemotherapy and vaccines. This literature review summarises the clinical trials for each form of systemic treatment in localised and metastatic melanoma and assesses the effectiveness of each by an evaluation and comparison of relevant clinical trials for each systemic modality. The main objective was to assess whether alternative forms of systemic therapy have improved the disease free and overall survival rates achieved with chemotherapy.

scholarly journals The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Antonio Faiella ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì ◽  
Martina Chiurazzi ◽  
Livia Onofrio
Keyword(s):  
Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Response To Treatment ◽  
Tyrosine Kinase Receptor ◽  
Mesenchymal Transition ◽  
Surface Receptors ◽  
Clinical Consequences

Background. c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. Conclusion. The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

scholarly journals Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials

2020 ◽  
Vol 50 (12) ◽  
pp. 1353-1363 ◽  
Author(s):  
Satoshi Nara ◽  
Minoru Esaki ◽  
Daisuke Ban ◽  
Takeshi Takamoto ◽  
Kazuaki Shimada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Bile Duct ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer ◽  
Adjuvant And Neoadjuvant Therapy ◽  
Duct Cancer

Abstract Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. However, because of the rarity of each disease, the efficacy of new drugs has been tested in groups of patients with different biliary tract cancers. In patients with metastatic or recurrent biliary tract cancer, recent randomized clinical trials revealed the non-inferiority of gemcitabine + S-1 and the superiority of gemcitabine + cisplatin + S-1 compared with gemcitabine + cisplatin in terms of overall survival, thereby establishing a new standard treatment. In the field of adjuvant therapy for biliary tract cancer, the British BILCAP (capecitabine compared with observation in resected biliary tract cancer) study revealed longer median overall survival in the capecitabine group than in the observation group in the per-protocol analysis (but not in the intention-to-treat analysis), bringing a shift toward postoperative management. Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.

CTONG1103: Final overall survival analysis of the randomized phase 2 trial of erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non–small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8502-8502
Author(s):  
Yi-Long Wu ◽  
Wenzhao Zhong ◽  
Ke-Neng Chen ◽  
Chun Chen ◽  
Fan Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Target Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stage Iiia

8502 Background: Median Overall survival (mOS) of stage IIIA resected NSCLC was 59.4 months (m) in CTONG 1104 adj gefitinib and 26.2m in SAKK neoadjuvant chemo trial. EMERGING-CTONG1103 showed neo-adjuvant/adjuvant erlotinib treatment significantly improved progression-free survival (PFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor ( EGFR) mutation-positive resectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Here, we present the final overall survival (OS) results from the study. Methods: This was a multicenter (17 centers in China) phase II randomized controlled trial of erlotinib（E）versus gemcitabine plus cisplatin (GC) as neoadjuvant/adjuvant therapy in pts with stage IIIA-N2 NSCLC with EGFR mutations in exon 19 or 21. From Dec 2011 to Dec. 2017, 386 pts sites were screened and 72 pts were randomly assigned to neoadjuvant/adjuvant E arm (N = 37) or GC arm(N = 35). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postoperative. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, downstaging rates of pathological lymph nodes, PFS, OS, safety, and tolerability. Data cut-off date was January, 29 2021. Results: With a median follow-up of 62.5 months, the median OS was 42.2months based on 47 (65.3%) events in ITT whole population. The mOS was 42.2m in E and 36.9m in GC (HR 0.83, 95%CI 0.47-1.47, p = 0.513). The 3-,5-year OS rate were 58.6%, 40.8% in E and 55.9%, 27.6% in GC respectively (p3-y = 0.819, p5-y = 0.252). All predefined subgroups including age, gender, EGFR mutation type had no significant difference in statistics between two arms. Subsequent treatments (ST) especially targeted therapy contributed most to OS (HR = 0.35,95% CI 0.18- 0.70). Median OS of pts receiving ST was 45.8m (n = 38), 34.6m in other treatment (n = 12), 24.6m in without ST (n = 15). For E mOS were 46.4 (n = 15; target therapy), 42.2m (n = 8; other) and 24.6m (n = 9; without, p = 0.021), for GC 42.6 (n = 23; target therapy), 30.1m (n = 4;other) and 24.6m(n = 6; without, p = 0.130). The RR was 53.3%, DCR 93.3%, mPFS 10.9m and mPPS 21.9m for patients with rechallenged EGFR TKI in E arm (n = 15). No novel unexpected SAE was observed during follow up. Conclusion: Erlotinib as neoadjuvant/adjuvant therapy for resected N2 NSCLC was feasibility and had a promising OS. The PFS survival advantage of E did not translate to OS difference in EMERGING trial (NCT01407822). Clinical trial information: NCT01407822.

scholarly journals Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients

2018 ◽  
Vol 10 ◽  
pp. 175883401774974 ◽  
Author(s):  
Niki Karachaliou ◽  
Maria Gonzalez-Cao ◽  
Guillermo Crespo ◽  
Ana Drozdowskyj ◽  
Erika Aldeguer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Free Survival ◽  
Melanoma Patients ◽  
Ifn Γ ◽  
Nsclc Patients ◽  
Important Marker

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.

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