Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay

2020 ◽  
Vol 21 (16) ◽  
pp. 1664-1671 ◽  
Author(s):  
Alessia Cimadamore ◽  
Francesco Massari ◽  
Matteo Santoni ◽  
Antonio Lopez-Beltran ◽  
Liang Cheng ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Response To Therapy ◽  
Primary Tumors ◽  
Biological Variables ◽  
Programmed Death ◽  
Metastatic Sites

Background: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. Objective: In this review, we focused on trials that investigated the administration of a PD-1 and PDL1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker. Conclusion: So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.

scholarly journals Current Treatments of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitors—2020 Update

2020 ◽  
Vol 9 (11) ◽  
pp. 3520
Author(s):  
Gerhard Jung ◽  
Daniel Benítez-Ribas ◽  
Ariadna Sánchez ◽  
Francesc Balaguer
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Host Immune System ◽  
Systemic Treatments

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the immune contexture of the tumor microenvironment (TME) have enabled the development of new systemic treatments that boost the host immune system against the tumor—the immune checkpoint inhibitors (ICI). These promising drugs have already shown astonishing efficacies in other cancer types and have raised new hope for the treatment of metastatic CRC (mCRC). In this review, we will summarize the results of the clinical trials that led to their accelerated approval by the U.S. Food and Drug Administration (FDA) in 2017, as well as all relevant recent studies conducted since then—some of which are not published yet. We will focus on therapeutic efficacy, but also discuss the available data for drug safety and security, changes in quality of life indicators and predictive biomarkers for treatment response. The burgeoning evidence for a potential use of ICIs in other settings than mCRC will also be mentioned. For each trial, we have made a preliminary assessment of the quality of clinical trial design and of the “European Society of Medical Oncology (ESMO) magnitude of clinical benefit” (ESMO-MCBS) in order to provide the first evidence-based recommendation to the reader.

Immunotherapy discontinuation and outcome: A multicenter real-life experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14075-e14075
Author(s):  
Maria Bassanelli ◽  
Diana Giannarelli ◽  
Maria RITA Migliorino ◽  
Marco Russano ◽  
Alain Gelibter ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Progressive Disease ◽  
Life Experience ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Best Response ◽  
Programmed Death

e14075 Background: Unlike chemotherapy, the optimum treatment duration with Immune checkpoint inhibitors (ICIs) is not clearly established. The aim of this study was to assess the outcome of patients (pts) who discontinued immune-based therapies for any reason except progressive disease. Methods: We conducted an observational, retrospective analysis of 46 consecutive pts with advanced cancer who received ICIs as clinically indicated, at eight Italian institutions. Tumor response to treatment was defined according to RECIST. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method. Results: 46 pts (median age 68 years [range 41-86]; male: 65.2%) with advanced cancer (n.39 non-small-cell lung cancer, n.15 renal cell carcinoma and n.2 melanoma) were treated with ICIs: 44 pts received programmed death 1 (PD-1) inhibitors (n.31 nivolumab, n.13 pembrolizumab) and 2 pts programmed death ligand 1 (PD-L1) (n.1 durvalumab, n.1 atezolizumab). A median of 8 cycles were administered [range 1 to 52]. 36 pts discontinued ICIs due to toxicities (diarrhoea, pneumonitis, hepatotoxicity) and 10 pts for reasons non immune-related. The median progression free survival (PFS) from the beginning of ICIs was 12.4 months (mo) [95% CI: 8.2-16.6] and the median OS was 20.0 mo (95% CI: 11.8-28.2). Median PFS from discontinuation of therapy was 5.0 mo [95% CI: 2.7-7.3] and median OS was 16.1 mo (95% CI: 5.4-26.8). Best response achieved according RECIST criteria were: 1 complete response (CR), 18 partial response, 21 stable disease (SD), 2 progressive disease (PR) and 3 non evaluable (NE). During interruption of ICIs 1 pts achieved a PR. Conclusions: This study shows the activity of ICIs, in terms of outcome and durable immune-response, in pts with advanced cancer even after treatment discontinuation.

scholarly journals Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 109
Author(s):  
Fang Yang ◽  
Jacqueline F. Wang ◽  
Yucai Wang ◽  
Baorui Liu ◽  
Julian R. Molina
Keyword(s):  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Small Cell Lung ◽  
Genomic Signatures ◽  
Programmed Death ◽  
Life Threatening ◽  
Clinical Responses ◽  
Novel Biomarkers ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.

scholarly journals Understanding Inflammasomes and PD-1/PD-L1 Crosstalk to Improve Cancer Treatment Efficiency

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3550
Author(s):  
Anaïs Perrichet ◽  
François Ghiringhelli ◽  
Cédric Rébé
Keyword(s):  
Cancer Treatment ◽  
Checkpoint Inhibitors ◽  
Response To Treatment ◽  
Immune Checkpoints ◽  
Cancer Growth ◽  
Inflammasome Activation ◽  
Treatment Efficiency ◽  
Programmed Death ◽  
Number Of Patients ◽  
Programmed Death 1

Inflammasomes and immune checkpoints have been shown to participate in carcinogenesis, cancer growth and response to treatment. Thus, targeting cytokines resulting from inflammasome activation, such as interleukin (IL)-1β, has emerged as a new tool in the therapeutic arsenal. Moreover, the use of checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 has revolutionized the treatment of some cancer patients. However, inflammasome activation and consecutive cytokine release only occurs in some chemotherapeutic treatments and immune checkpoint inhibitors only work for a restricted number of patients, thus limiting the use of therapies targeting these pathways. Expanding knowledge about the inefficiency of these therapies recently brought forward the hypothesis of targeting both pathways. In this review, we provide an overview of the crosstalk between inflammasomes and programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) that might explain how these two pathways are mutually dependent, and perhaps why targeting only one of them leads to inefficiency of cancer treatment in some patients.

scholarly journals Predictive biomarkers of inhibitors immune checkpoints therapy in malignant tumors

2021 ◽  
Vol 8 (2) ◽  
pp. 73-83
Author(s):  
M. V. Kiselevsky ◽  
I. V. Samoylenko ◽  
O. V. Zharkova ◽  
N. V. Ziganshina ◽  
A. A. Petkevich ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Predictive Biomarkers ◽  
Peripheral Blood Lymphocytes ◽  
Immune Checkpoints ◽  
Russian Science ◽  
Programmed Death ◽  
Number Of Patients ◽  
Russian Science Citation Index

Immune checkpoint inhibitors (ICT) therapy is a successful immunotherapy (IT) strategy that is quite effective in a number of patients with non-small cell lung cancer, melanoma, bladder cancer, breast cancer and others. Nevertheless, there is a need in predictive markers for ICT therapy for personalized IT as far as there is a large group of patients, the proportion of which varies depending on the tumor, who do not have a clinical response to such therapy. The review summarizes the theoretical aspects and results of clinical trials dedicated to various clinical efficiency predictor using modern databases. As a result of the analysis it is established that the main candidates for the role of such markers are tumor infiltrating lymphocytes and their subpopulations, peripheral blood lymphocytes (PBL) and their subpopulations. PD1 (programmed death receptor 1) and PDL1 (programmed death receptor ligand 1) expression in tumor tissue can also be important for predicting IT efficiency. The most promising predictive biomarker meaning the most clinically relevant is a combination of the PBL subpopulations study and PD1 and PDL1 expression on the tumor cells.PubMed, Scopus, Web of Science, eLibrary, Russian Science Citation Index databases were searched for the available appropriate literature reports. The authors included 82 in the given review.

Human chorionic gonadotropin (HCG) as a biomarker in sarcoma: A systematic review.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22503-e22503
Author(s):  
Martin W. Schoen ◽  
Ahmad Al-Taee ◽  
Bassel Jallad
Keyword(s):  
Systematic Review ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Low Cost ◽  
Elevated Serum ◽  
Germ Cell Tumors ◽  
Response To Therapy ◽  
Response To Treatment ◽  
High Grade ◽  
Poorly Differentiated

e22503 Background: Human chorionic gonadotropin (HCG) has been reported in soft tissue sarcoma and osteosarcoma. In some patients, the ectopic production of HCG can lead to delays in diagnosis due to concern for pregnancy or germ cell tumors. Methods: We performed a systematic review of the scientific literature in English using PubMed to categorize cases of sarcoma search terms were HCG, sarcoma, human chorionic gonadotropin and osteosarcoma. Cases of sarcoma associated with HCG production were identified and further categorized by type and grade of tumor. Initial HCG, Peak HCG, response to therapy and case outcome were collected when available. We also included a case seen at our institution of osteosarcoma with ectopic HCG production. Results: We identified 21 manuscripts and 23 cases of patients with both sarcoma and elevated serum HCG. 10/23 patients were male (43%).The most frequent type of sarcoma was osteosarcoma with 9/23 (39%) of cases, leiomyosarcoma was identified in 7/23 (30%) and liposarcoma in 3/23 (13%) of cases. When described, all tumors were high grade or poorly differentiated. 20/23 tumors (87%) had HCG expression of the tumor by immunohistochemistry. Mean initial HCG was 3607 with a peak value of 6188. In 19 cases, HCG was used to monitor disease after treatment and 14/19 (74%) responded with a decrease in HCG after treatment. Of responders, 3 patients were considered cured and 2 were put into remission, while none of the patients without response survived. Overall, outcomes were poor with 16/23 (70%) deaths within one year. Conclusions: Sarcomas that secrete HCG tend to be high grade, poorly differentiated and appear to portend a poor prognosis. When expressed, HCG can be used as a marker of disease and response to therapy. Oncologists should consider checking HCG as a potentially low-cost marker of prognosis and response to treatment in patients with sarcoma. [Table: see text]

Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study.

1989 ◽  
Vol 7 (5) ◽  
pp. 638-647 ◽  
Author(s):  
P Grundy ◽  
N Breslow ◽  
D M Green ◽  
K Sharples ◽  
A Evans ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Wilms Tumor ◽  
Survival Rates ◽  
Initial Therapy ◽  
Chemotherapeutic Agents ◽  
Stage I ◽  
Prognostic Features ◽  
Favorable Histology ◽  
Tumor Study ◽  
Unilateral Disease

The characteristics of 367 stage I-IV National Wilms' Tumor Study (NWTS) children who relapsed after initial treatment for unilateral disease in the second and third NWTS trials (NWTS-2 and -3) were analyzed to identify features predictive of survival. Although modifications in initial therapy resulted in a lower rate of first relapse in these two studies compared with NWTS-1, all previously identified prognostic factors after relapse remained statistically significant predictors of survival. Tumor histology, length of initial remission, initial therapy with two v three drugs, and site of relapse each were independently predictive of postrelapse survival. The 3-year postrelapse survival for all 367 patients was 30% +/- 3%; however, subgroups classified by these prognostic factors were identified that had 3-year postrelapse survival rates of greater than 40%. These subgroups included patients who had tumors of favorable histology (FH) that recurred (1) only in the lungs, (2) in the abdomen when radiotherapy (RT) was not initially given, or (3) that were originally stage I, (4) that were originally treated with only two drugs, or (5) that recurred 12 months or more after diagnosis. These results were achieved with the use of standard treatments, ie, surgery, RT, and chemotherapy using dactinomycin (AMD), vincristine (VCR), and Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH). It is suggested that patients in these groups might be managed with aggressive use of conventional therapies until newer chemotherapeutic agents and drug combinations are shown to be more effective. Patients with adverse prognostic features at relapse have a poor survival expectancy with standard measures. Salvage attempts for these patients are better based on experimental approaches.

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