Targeting LAG-3 and PD-1 With Relatlimab and Nivolumab: A New Option Under Study in Advanced Melanoma
Immune checkpoint inhibition has been established as an effective treatment for patients with metastatic melanoma. A novel immunotherapeutic combination—this one targeting the LAG-3 (lymphocyte-activation gene 3) and PD-1 immune checkpoints—delayed time to disease progression significantly more...
High-Dose Interferon or Ipilimumab vs Pembrolizumab for High-Risk Resected Melanoma
Patients with high-risk melanoma who had a course of pembrolizumab had longer recurrence-free survival than patients who received either ipilimumab or high-dose interferon after surgery. These findings of a large SWOG Cancer Research Network clinical trial, S1404, were presented by Grossmann et al...
Extended Follow-up of Nivolumab/Ipilimumab for Metastatic Melanoma
In the longest follow-up results from a clinical trial of combination immunotherapy for metastatic melanoma, investigators report that nearly half the patients who received the drugs nivolumab and ipilimumab were alive at a median of 6.5 years after treatment. These long-term results from the...
Evan J. Lipson, MD, on Melanoma: Relatlimab and Nivolumab in First-Line Treatment of Advanced Disease
Evan J. Lipson, MD, of Johns Hopkins University, discusses primary phase III results from the RELATIVITY-047 study, which showed that relatlimab plus nivolumab as a fixed-dose combination may improve progression-free survival compared with nivolumab monotherapy in patients with advanced melanoma. This is the first study to demonstrate a benefit from dual inhibition of the LAG-3 and PD-1 pathways.
Cemiplimab-rwlc for Patients With Locally Advanced Basal Cell Carcinoma After Hedgehog Inhibitor Therapy
As reported in The Lancet Oncology by Stratigos et al, findings in a subgroup of a phase II trial have shown that the PD-1 antibody cemiplimab-rwlc produces enduring responses in patients with locally advanced basal cell carcinoma who had progressive disease on or intolerance to prior hedgehog...
Ipilimumab Plus Anti–PD-1 Therapy vs Ipilimumab Alone for Patients With Advanced Melanoma Resistant to Anti–PD-1/PD-L1 Monotherapy
In a retrospective cohort study reported in The Lancet Oncology, da Silva et al found that better outcomes were achieved with the combination of an anti–PD-1 agent plus ipilimumab vs ipilimumab alone in patients with advanced melanoma who were resistant to prior anti–PD-1 or anti–PD-L1 ...
First-Line Nivolumab/Relatlimab vs Nivolumab Alone for Advanced Melanoma
Treatment with the anti–PD-1 therapy nivolumab plus the LAG-3–blocking antibody relatlimab extended time to disease progression for patients with previously untreated, unresectable, or metastatic melanoma. Findings from the RELATIVITY-047 trial were presented by Evan J. Lipson, MD, and colleagues...
Expert Point of View: Stefania Scala, MD
Formal discussant Stefania Scala, MD, of the Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, was impressed by the findings of KEYNOTE-629. “The second interim analysis for the locally advanced disease cohort and updated data for the recurrent/metastatic disease cohort of KEYNOTE-629 had ...
Single-Agent Pembrolizumab Yields High Response Rates in Patients With Cutaneous Squamous Cell Carcinoma
Single-agent pembrolizumab achieved durable responses and promising survival in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, according to the second interim analysis of the phase II KEYNOTE-629 study, which was presented at the virtual American...
Lifileucel for Patients With Previously Treated Metastatic Melanoma
In a cohort of a phase II study reported in the Journal of Clinical Oncology, Amod A. Sarnaik, MD, and colleagues found that the tumor-infiltrating lymphocyte therapy lifileucel produced durable responses in patients with metastatic melanoma previously treated with checkpoint inhibitors and BRAF-...
Mutational Profile of Acral Nevi May Differ From Acral Melanoma
Melanocytic nevi are nonmalignant growths that arise from pigment-producing cells of the skin. They are mostly found in sun-exposed areas; however, they also can be found in sun-protected areas, such as the palms, soles of the feet, and nail beds, where they are known as acral nevi. While the...
Pembrolizumab/Ipilimumab After Disease Progression on PD-1/PD-L1 Inhibitor Therapy in Advanced Melanoma
In a phase II trial reported in the Journal of Clinical Oncology, Olson et al found that pembrolizumab plus low-dose ipilimumab produced durable responses in patients with advanced melanoma whose disease had progressed on immediate prior PD-1 or PD-L1 inhibitor therapy. Study Details In the U.S....
Study Finds Adjuvant Immunotherapy of Benefit to Patients With Stage IIB/C Melanoma
A significant survival advantage accrued to patients with stage IIB and IIC cutaneous melanoma who received adjuvant immunotherapy, a large retrospective cohort study reported at the Society of Surgical Oncology (SSO) 2021 International Conference on Surgical Cancer Care.1 The 3-year overall...
Expert Point of View: Alexander Eggermont, MD, PhD
Formal discussant of CheckMate 915, Alexander Eggermont, MD, PhD, Chief Scientific Officer at the Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands, suggested that the lower doses of ipilimumab used in the current study may explain the lack of effect on relapse-free survival. The...
Comparing Nivolumab Plus Ipilimumab vs Nivolumab Alone in Resected Stage III to IV Melanoma
The addition of ipilimumab to nivolumab failed to improve outcomes compared with nivolumab alone as adjuvant therapy for resected melanoma, according to the results of the CheckMate 915 trial, presented at the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting...
Expert Point of View: Caroline Robert, MD
This is the first randomized trial that is positive for overall survival in uveal melanoma, and I’m very excited about the results, which I consider seminal and practice-changing,” said formal discussant Caroline Robert, MD, of Gustave Roussy, Villejuif, France. “This is such a rare tumor, but it...
Tebentafusp Shows Overall Survival Benefit in First-Line Treatment of Metastatic Uveal Melanoma
Treatment with tebentafusp—a novel bispecific fusion protein—reduced the risk of death from metastatic uveal melanoma by half, compared with available treatments, in a phase III study presented at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.1 This is the first...
Health-Related Quality of Life With Adjuvant Pembrolizumab vs Placebo in Resected Stage III Melanoma
As reported in The Lancet Oncology by Andrew Bottomley, PhD, and colleagues, an analysis of the phase III EORTC 1325-MG/KEYNOTE-054 trial showed no clinically significant decline in health-related quality of life (HRQoL) with adjuvant pembrolizumab vs placebo in resected high-risk stage III...
Cemiplimab-rwlc for Locally Advanced and Metastatic Basal Cell Carcinoma
On February 9, 2021, cemiplimab-rwlc was granted regular approval for the treatment of patients with locally advanced basal cell carcinoma (BCC) who were previously treated with a Hedgehog pathway inhibitor or for whom this type of therapy is not appropriate and granted accelerated approval for...
Improvement in Survival With Adjuvant Pembrolizumab for Resected Stage III Melanoma
As reported in The Lancet Oncology by Alexander M.M. Eggermont, MD, and colleagues, the pivotal phase III EORTC 1325/KEYNOTE-054 trial has shown significant improvement in the secondary endpoint of distant metastasis–free survival—as well as continued benefit in the primary endpoint of...
Georgina V. Long, MD, PhD, on Melanoma: Nivolumab Plus Ipilimumab vs Nivolumab Alone
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, University of Sydney, discusses results of the CheckMate 915 trial, which may reinforce nivolumab as an adjuvant standard of care in patients with stage IIIB–D/IV melanoma, with or without complete lymphadenectomy (Abstract CT004).
Estimated Shifts in Cancer Incidence and Death Over Next 2 Decades
In the next 2 decades, rankings of incidence and death across cancer types in the United States will undergo important changes, according to new research published by Lola Rahib, PhD, and colleagues in JAMA Network Open. The study estimates that pancreatic cancer is on course to become the...
Tumor Mutational Burden as Predictor of Immune Response: Variance Between Female and Male Patients With Melanoma
Tumor mutational burden (TMB) was an accurate predictor of response to treatment with immune checkpoint inhibitors for female patients with melanoma, but not for male patients, according to results of a study presented by Sinha et al during the virtual American Association for Cancer Research...
Samra Turajlic, MBBS, PhD, on Understanding Metastatic Disease in Renal Cancer and Melanoma
Samra Turajlic, MBBS, PhD, of The Francis Crick Institute, discusses our limited understanding of metastases in terms of the timing of dissemination, the many metastatic phenotypes and varieties of seeding, as well as how the spread of cancer evades the immune system and resists treatment. Expanding this knowledge base is critical to better managing malignant disease.
Jessica C. Hassel, MD, on Uveal Melanoma: Comparing Tebentafusp With Standard Therapies
Jessica C. Hassel, MD, of University Hospital Heidelberg, discusses phase III results of a study that compared tebentafusp, a bispecific fusion protein, with investigator’s choice in patients with metastatic uveal melanoma. Tebentafusp nearly halved the risk of death among patients in the trial with this rare eye cancer (Abstract CT002).
Tebentafusp: First Treatment to Improve Overall Survival in Metastatic Uveal Melanoma
Treatment with tebentafusp, a novel bispecific fusion protein, reduced the risk of death from metastatic uveal melanoma at 14 months by half, compared with available treatments, in a phase III study presented by Piperno-Neumann et al at the virtual American Association for Cancer Research (AACR)...
Unselected Autologous Tumor-Infiltrating Lymphocyte Therapy for Metastatic Cutaneous Melanoma
Treatment with unselected autologous tumor-infiltrating lymphocytes (TILs) showed early clinical efficacy among patients with advanced melanoma, according to results presented by Hawkins et al during week 1 of the virtual American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract ...
Adverse Events in Patients With Melanoma Treated With Ipilimumab: Results of a Toxicity Monitoring Program
In a single-institution study reported in JCO Oncology Practice, Menjak et al found that a nurse-led telephone surveillance program for toxicity associated with ipilimumab in patients with metastatic melanoma led to earlier identification of toxicities and earlier intervention, with an apparent...
April K. Salama, MD, on Managing Melanoma Brain Metastases
April K. Salama, MD, of Duke Cancer Institute, discusses the shift in recent years, as more effective therapies have become available, toward integrating systemic upfront treatment of patients with brain metastases from cutaneous melanoma; pivotal studies that have provided key data; and the need for a multidisciplinary approach incorporating medical, surgical, and radiation oncology.
Screening and Education in Melanoma-Prone Families May Improve Early Detection of Disease
Among patients at high risk of melanoma, those who received routine skin cancer screening and education about skin self-exams were significantly more likely to be diagnosed with thinner and earlier-stage melanomas, according to results published by Michael Sargen, MD, and colleagues in Cancer...
Chronic Immune-Related Adverse Events Associated With Adjuvant Immunotherapy for Advanced Melanoma
In a retrospective cohort study reported in JAMA Oncology, Patrinely et al found that chronic immune-related adverse events occurred in a high proportion of patients receiving adjuvant PD-1–targeted therapy for high-risk resected melanoma and frequently persisted even during prolonged follow-up....
Surgical Management of Melanoma With the Advent of Adjuvant Systemic Therapy
The results of a large cohort study suggest that a proportion of patients with cutaneous melanoma could potentially avoid sentinel node biopsy, according to data presented by Moncrieff et al at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care (Abstract 59)....
Susan M. Swetter, MD, on Molecular Testing for Cutaneous Melanoma
Susan M. Swetter, MD, of Stanford Cancer Institute, discusses molecular prognostic tests for cutaneous melanoma, which may improve staging accuracy, reduce unnecessary sentinel lymph node biopsies, and inform decisions on surveillance imaging and/or adjuvant therapy.
Utilization and Survival Benefit of Adjuvant Immunotherapy for Resected High-Risk Stage II Melanoma
An observational study of 10,592 patients from the National Cancer Database with stage IIB/IIC melanoma who had undergone surgical resection demonstrated a significant survival advantage with immunotherapy. The research was presented by Wong et al at the Society of Surgical Oncology 2021...
Nomograms to Predict Local, Regional, and Distant Recurrence in Patients With Thin Melanomas
As reported in the Journal of Clinical Oncology, El Sharouni et al have developed nomograms to predict local, regional, and distant recurrence in patients with T1 melanomas. Study Details The study used data from a Dutch population-based cohort of 25,930 patients to develop the nomograms. The...
Study Identifies Mechanisms Tied to Immunotherapy Resistance Among Patients With Melanoma
Researchers have created a new technique that may help to uncover mechanisms cancer cells use to evade immunotherapies, which could lead to the development of more effective treatments. Investigators tested their new technique with cancer cells and matching immune cells from patients with melanoma...
Association of BRAF V600–Mutant ctDNA With Outcomes in Patients With Advanced Melanoma Receiving Dabrafenib or Dabrafenib/Trametinib
In a study reported in The Lancet Oncology, Syeda et al found that higher BRAF V600–mutant cell-free circulating tumor DNA (ctDNA) levels prior to and during treatment with dabrafenib or dabrafenib/trametinib were associated with poorer outcomes among patients with advanced melanoma. Study Details...
Fecal Microbiota Transplants May Help Patients With Advanced Melanoma Respond to Immunotherapy
For patients with melanoma who do not respond to treatment with immunotherapy, adjusting the composition of microorganisms in the intestines through the use of fecal transplants may aid in overcoming resistance to therapy. These findings were published by Davar et al in Science. In the study, some...
FDA Approves Cemiplimab-rwlc for Locally Advanced and Metastatic Basal Cell Carcinoma
On February 9, the U.S. Food and Drug Administration (FDA) granted regular approval to cemiplimab-rwlc (Libtayo) for patients with locally advanced basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate. The FDA also granted...
High-Risk Cutaneous Squamous Cell Carcinomas: The Present and Future
Cutaneous squamous cell carcinoma is the second most common type of skin cancer, with more than 1 million cases diagnosed in the United States annually.1 Historically, cutaneous squamous cell carcinoma is grouped together with basal cell carcinoma and collectively referred to as nonmelanoma skin...
FDA Pipeline: Priority Reviews for Immunotherapies in Gastric Cancers, Anal Cancer
The U.S. Food and Drug Administration (FDA) recently granted Priority Review to nivolumab as either adjuvant or first-line therapy in several types of gastric cancers, as well as to a novel PD-1 inhibitor for locally advanced or metastatic squamous cell carcinoma of the anal canal. The FDA also...
Small Study Finds Personalized Neoantigen Vaccines May Result in Durable Immune Response for Patients With Melanoma
Four years after patients with melanoma were treated with a personalized cancer vaccine, the immune response caused by the vaccine remained robust and effective in keeping cancer cells under control, according to a new study published by Hu et al in Nature Medicine. The findings demonstrate the...
First-Line Nivolumab/Ipilimumab in Metastatic Uveal Melanoma
In a Spanish phase II trial reported in the Journal of Clinical Oncology, Piulats et al found that nivolumab/ipilimumab produced a “modest” improvement in overall survival vs historical rates achieved with chemotherapy as first-line treatment for patients with metastatic uveal melanoma ineligible...
FDA Pipeline: Two Fast Track Designations for Cavrotolimod in Nonmelanoma Skin Cancers
The U.S. Food and Drug Administration (FDA) has granted two Fast Track designations to cavrotolimod (AST-008). The designations include cavrotolimod in combination with anti–PD-1 therapy for the treatment of patients with locally advanced or metastatic Merkel cell carcinoma refractory to prior...
New Study Investigates Role of Ultraviolet Radiation in Conjunctival Melanoma
Ultraviolet (UV) radiation may contribute to the development of a rare type of eye cancer, conjunctival melanoma, according to research published by Mundra et al in Nature Communications. The new study has revealed similar genetic changes in patients with conjunctival melanoma to those with...
New Study Explores the Use of Focused Ultradeep DNA Sequencing to Quantify Skin Cancer Risk
Recent research has shed new light on the carcinogenic effect of exposure to ultraviolet (UV) radiation, laying the groundwork for improvements in skin cancer risk stratification and prevention. A study published by Lei Wei, PhD, and colleagues in Science Advances detailed a method to measure the...
Intratumoral Injections May Boost Neoadjuvant Response in Resectable Melanoma
Studies reported at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting, which was held virtually, showed promise for the use of intratumoral injections of novel immunotherapies in treating advanced, resectable melanoma. In the 3-year interim analysis of a global phase II randomized...
Novel Combination Under Study in First-Line Treatment of Metastatic Melanoma
A first-line regimen combining the novel interleukin-2 (Il-2) agonist bempegaldesleukin (NKTR-214) with nivolumab showed encouraging clinical activity in patients with metastatic melanoma in the phase I/II PIVOT-02 trial, according to a presentation during the 2020 Annual Meeting of the Society for ...
ESMO Immuno-Oncology 2020: First-Line Anti–PD-1 Therapy vs BRAF/MEK Inhibition for Advanced BRAF V600–Mutated Melanoma
Findings from a propensity-matched survival analysis presented by van Breeschoten et al at the European Society for Medical Oncology (ESMO) Immuno-Oncology Virtual Congress 2020 (Abstract 37P) suggest that patients with advanced melanoma and a BRAF V600 mutation derive an enhanced survival benefit...
ESMO Immuno-Oncology 2020: Tebentafusp Shows Activity in Metastatic Uveal Melanoma
Tebentafusp is a novel bispecific molecule consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100-positive cells. The agent showed clinical benefit, including target lesion reduction, in patients with metastatic uveal melanoma,...
