scholarly journals The therapeutic landscape of advanced melanoma

2020 ◽  
Vol 13 (3) ◽  
pp. 306-308 ◽  
Author(s):  
Erika Richtig
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Short Review ◽  
Advanced Melanoma ◽  
Oncolytic Viruses ◽  
Therapeutic Landscape ◽  
The World ◽  
Melanoma Treatment ◽  
Tumor Entities

Summary The therapeutic landscape of advanced and metastatic melanoma has changed dramatically in the last ten years. Targeted therapies as well as checkpoint inhibitors and oncolytic viruses have launched a broad revolution within this field. First presented at ASCO 2011, changes in melanoma treatment giving “light at the end of the tunnel” have also changed the treatment of many other tumor entities. So oncologists all over the world can offer their patients these treatment options with higher efficacy than we ever had. But despite all optimism we are still losing about half of our patients with metastatic melanoma along the way. In this short review the therapeutic landscape of advanced melanoma is described.

scholarly journals Novel immune checkpoints beyond PD-1 in advanced melanoma

2021 ◽  
Author(s):  
Nina Zila ◽  
Christoph Hoeller ◽  
Verena Paulitschke
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Short Review ◽  
Therapy Resistance ◽  
Advanced Melanoma ◽  
Immune Checkpoints ◽  
Malignant Diseases ◽  
Foreseeable Future ◽  
Cell Responses ◽  
Therapeutic Landscape

SummaryIn malignant diseases, targeting of immune checkpoints successfully changed the therapeutic landscape and helped to unleash anti-tumor T cell responses, resulting in durable clinical outcomes, but only in up to 50% of patients. The success of these therapies and the need to overcome intrinsic and acquired therapy resistance stimulated research to identify new pathways and targets. Numerous clinical trials are currently evaluating novel checkpoint inhibitors or recently developed strategies like modulating the tumor microenvironment, mostly in combination with approved therapies. This short review briefly discusses promising therapeutic targets, currently still under investigation, with the chance to realize clinical application in the foreseeable future.

scholarly journals Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives

2020 ◽  
Vol 123 (6) ◽  
pp. 885-897
Author(s):  
Mark R. Middleton ◽  
Christoph Hoeller ◽  
Olivier Michielin ◽  
Caroline Robert ◽  
Caroline Caramella ◽  
...  
Keyword(s):  
Immune Response ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Unmet Need ◽  
Systemic Exposure ◽  
Oncolytic Viruses ◽  
Current Status ◽  
Local Concentration ◽  
Major Step

Abstract The emergence of human intratumoural immunotherapy (HIT-IT) is a major step forward in the management of unresectable melanoma. The direct injection of treatments into melanoma lesions can cause cell lysis and induce a local immune response, and might be associated with a systemic immune response. Directly injecting immunotherapies into tumours achieves a high local concentration of immunostimulatory agent while minimising systemic exposure and, as such, HIT-IT agents are associated with lower toxicity than systemic immune checkpoint inhibitors (CPIs), enabling their potential use in combination with other therapies. Consequently, multiple HIT-IT agents, including oncolytic viruses, pattern-recognition receptor agonists, injected CPIs, cytokines and immune glycolipids, are under investigation. This review considers the current clinical development status of HIT-IT agents as monotherapy and in combination with systemic CPIs, and the practical aspects of administering and assessing the response to these agents. The future of HIT-IT probably lies in its use in combination with systemic CPIs; data from Phase 2 trials indicate a synergy between HIT-IT and CPIs. Data also suggest that the addition of HIT-IT to a CPI might generate responses in CPI-refractory tumours, thereby overcoming resistance and addressing a current unmet need in unresectable and metastatic melanoma for treatment options following progression after CPI treatment.

A patient with melanoma that became sensitized to immunotherapy after treatment with a CDK4/6 inhibitor

Immunotherapy ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 861-867
Author(s):  
Jacob Zaemes ◽  
Ali Alzeer ◽  
Kathryn Villa ◽  
Michael Atkins
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Poor Response ◽  
Sustained Response ◽  
Mek Inhibitors ◽  
Preclinical Data ◽  
Melanoma Treatment

Background: Despite the profound effect that checkpoint inhibitors and BRAF/MEK inhibitors have had on survival in patients with metastatic melanoma, treatment options remain limited for those who demonstrate poor response or develop resistance to these modalities. The prospect of tumor sensitization to these treatments is therefore an attractive one. Results: We describe the case of a patient who developed a sustained response to trametinib and pembrolizumab, despite prior resistance to both these therapies, after receiving treatment with a CDK4/6 inhibitor. Discussion: We further outline the preclinical data supporting a possible role for the use of CDK4/6 inhibitors in tumor sensitization to immunotherapy.

scholarly journals The Emerging Therapeutic Landscape of Advanced Melanoma

2018 ◽  
Vol 24 (5) ◽  
pp. 549-558 ◽  
Author(s):  
Vanessa Henriques ◽  
Teresa Martins ◽  
Wolfgang Link ◽  
Bibiana I. Ferreira
Keyword(s):  
Skin Cancer ◽  
Metastatic Melanoma ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Treatment Modalities ◽  
Specific Therapy ◽  
Novel Treatments ◽  
The Past ◽  
Therapeutic Landscape ◽  
Paradigm Shifting

Melanoma is the deadliest form of skin cancer being responsible for 80% of skin cancer deaths. Furthermore, the incidence of metastatic melanoma has increased over the past three decades with a mortality rate that continues to rise faster than most of all other cancers. The last few years have witnessed an unparalleled change in treatment options for patients with metastatic melanoma by the development of new therapeutic strategies like targeted therapies and immunotherapies that highly improved the patient’s prognosis. Despite the paradigm- shifting success of these novel treatments, their effectiveness is still limited by intrinsic or acquired resistance. The objective of this review is to provide an overview of the new available treatment modalities, criteria to select patients who might benefit from a specific therapy, mechanisms of innate and acquired resistance to these treatments and to discuss strategies to overcome drug resistance.

scholarly journals Immuno-Oncotherapeutic Approaches in Advanced Hepatocellular Carcinoma

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 447
Author(s):  
Robin Park ◽  
Fariha Eshrat ◽  
Mohammed Al-Jumayli ◽  
Azhar Saeed ◽  
Anwaar Saeed
Keyword(s):  
Hepatocellular Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Oncolytic Viruses ◽  
Advanced Hepatocellular Carcinoma ◽  
T Cell Therapy ◽  
Fda Approval ◽  
Car T Cell Therapy ◽  
Pivotal Study ◽  
Extensive Growth

Advanced hepatocellular carcinoma has limited treatment options, but there has been extensive growth recently with cabozantinib, regorafenib, lenvatinib, nivolumab, atezolizumab, and bevacizumab, which are some of the treatments that have received FDA approval just over the last three years. Because HCC tumor microenvironment is potentially immunogenic and typically characterized by inflammation, immunotherapy has been proposed as a potential novel therapeutic approach, which has prompted studies in advanced HCC patients investigating various immune-therapeutic strategies such as CAR-T cell therapy, checkpoint inhibitors, and onco-vaccines. The anti-PD-1 checkpoint inhibitors nivolumab and pembrolizumab have been FDA approved as a second line treatment in patients who progressed or are intolerant to Sorafenib. To build up on the success of PD-1 monotherapy, combinatorial regimens with PD-1/PD-L1 inhibitors plus VEGF targeted agents have shown positive results in various malignancies including HCC. The combination of atezolizumab plus bevacizumab is the new addition to the HCC treatment armamentarium following a pivotal study that demonstrated an improvement in OS over frontline sorafenib. Other novel immune-based approaches and oncolytic viruses are in the early phases of clinical evaluation. These innovative approaches enhance the intensity of cancer-directed immune responses and will potentially impact the outlook of this aggressive disease.

scholarly journals Current Advances in the Treatment of BRAF-Mutant Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 482 ◽  
Author(s):  
Hima Patel ◽  
Nour Yacoub ◽  
Rosalin Mishra ◽  
Aaron White ◽  
Long Yuan ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Individual Response ◽  
Term Survival ◽  
Mek Inhibitors ◽  
Development Of Resistance ◽  
Patient Responses ◽  
Braf Mutant

Melanoma is the most lethal form of skin cancer. Melanoma is usually curable with surgery if detected early, however, treatment options for patients with metastatic melanoma are limited and the five-year survival rate for metastatic melanoma had been 15–20% before the advent of immunotherapy. Treatment with immune checkpoint inhibitors has increased long-term survival outcomes in patients with advanced melanoma to as high as 50% although individual response can vary greatly. A mutation within the MAPK pathway leads to uncontrollable growth and ultimately develops into cancer. The most common driver mutation that leads to this characteristic overactivation in the MAPK pathway is the B-RAF mutation. Current combinations of BRAF and MEK inhibitors that have demonstrated improved patient outcomes include dabrafenib with trametinib, vemurafenib with cobimetinib or encorafenib with binimetinib. Treatment with BRAF and MEK inhibitors has met challenges as patient responses began to drop due to the development of resistance to these inhibitors which paved the way for development of immunotherapies and other small molecule inhibitor approaches to address this. Resistance to these inhibitors continues to push the need to expand our understanding of novel mechanisms of resistance associated with treatment therapies. This review focuses on the current landscape of how resistance occurs with the chronic use of BRAF and MEK inhibitors in BRAF-mutant melanoma and progress made in the fields of immunotherapies and other small molecules when used alone or in combination with BRAF and MEK inhibitors to delay or circumvent the onset of resistance for patients with stage III/IV BRAF mutant melanoma.

Immunotherapy for advanced melanoma: current situation in Japan

2020 ◽  
Vol 51 (1) ◽  
pp. 3-9
Author(s):  
Junji Kato ◽  
Hisashi Uhara
Keyword(s):  
Uveal Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Advanced Melanoma ◽  
Current Evidence ◽  
Clinical Effects ◽  
Durable Response ◽  
Term Survival

Abstract Treatment with immune checkpoint inhibitors provides long-term survival for patients with advanced melanoma. Improvements in the overall survival of advanced melanoma patients have been achieved with anti-PD-1 monotherapy and anti-PD-1+ CTLA4 combination therapy, but there are still many issues to resolve. Acral, mucosal and uveal melanoma have been less responsive to immune checkpoint inhibitors than cutaneous melanoma. For patients who have achieved a good response, it is still not known how long the anti-PD-1 therapy should be administered. Moreover, there is limited treatment for patients who relapse during or after adjuvant anti-PD-1 therapy. Here, we review the current evidence regarding the clinical effects of immunotherapy for advanced melanoma. Moreover, we review previous studies of acral, mucosal and uveal melanoma, and we discuss the recent findings regarding durable response after the cessation of anti-PD-1 therapy, and treatment options for recurrence after adjuvant therapy.

scholarly journals Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1532 ◽  
Author(s):  
Malfitano ◽  
Somma ◽  
Prevete ◽  
Portella
Keyword(s):  
Thyroid Carcinoma ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Oncolytic Viruses ◽  
Cancer Models ◽  
Poorly Differentiated ◽  
Immunosuppressive Microenvironment

Virotherapy is a novel cancer treatment based on oncolytic viruses (OVs), which selectively infect and lyse cancer cells, without harming normal cells or tissues. Several viruses, either naturally occurring or developed through genetic engineering, are currently under investigation in clinical studies. Emerging reports suggesting the immune-stimulatory property of OVs against tumor cells further support the clinical use of OVs for the treatment of lesions lacking effective therapies. Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), have a poor prognosis and limited treatment options. Therefore, several groups investigated the therapeutic potential of OVs in PDTC/ATC models producing experimental data sustaining the potential clinical efficacy of OVs in these cancer models. Moreover, the presence of an immunosuppressive microenvironment further supports the potential use of OVs in ATC. In this review, we present the results of the studies evaluating the efficacy of OVs alone or in combination with other treatment options. In particular, their potential therapeutic combination with multiple kinases inhibitors (MKIs) or immune checkpoint inhibitors are discussed.

scholarly journals Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma

2021 ◽  
pp. JCO.21.00612
Author(s):  
Amod A. Sarnaik ◽  
Omid Hamid ◽  
Nikhil I. Khushalani ◽  
Karl D. Lewis ◽  
Theresa Medina ◽  
...  
Keyword(s):  
Disease Control ◽  
Metastatic Melanoma ◽  
Treatment Options ◽  
Objective Response ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
Disease Control Rate ◽  
High Dose ◽  
Tumor Infiltrating Lymphocyte ◽  
Programmed Death

PURPOSE Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product. METHODS We conducted a phase II open-label, single-arm, multicenter study in patients with advanced melanoma who had been previously treated with checkpoint inhibitor(s) and BRAF ± MEK targeted agents. Lifileucel was produced from harvested tumor specimens in central Good Manufacturing Practice facilities using a streamlined 22-day process. Patients received a nonmyeloablative lymphodepletion regimen, a single infusion of lifileucel, and up to six doses of high-dose interleukin-2. The primary end point was investigator-assessed objective response rate (ORR) per RECIST, version 1.1. RESULTS Sixty-six patients received a mean of 3.3 prior therapies (anti–programmed death 1 [PD-1] or programmed death ligand 1 [PD-L1]: 100%; anticytotoxic T-lymphocyte-associated protein-4: 80%; BRAF ± MEK inhibitor: 23%). The ORR was 36% (95% CI, 25 to 49), with two complete responses and 22 partial responses. Disease control rate was 80% (95% CI, 69 to 89). Median duration of response was not reached after 18.7-month median study follow-up (range, 0.2-34.1 months). In the primary refractory to anti–PD-1 or PD-L1 therapy subset, the ORR and disease control rate were 41% (95% CI, 26 to 57) and 81% (95% CI, 66 to 91), respectively. Safety profile was consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2. CONCLUSION Lifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy, including the primary refractory to anti–PD-1 or PD-L1 therapy subset.

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