Keith T. Flaherty, MD, on Results From the DREAMseq Trial
Invited discussant of the phase III DREAMseq trial, Keith T. Flaherty, MD, said the findings still leave room for nuanced decision-making.1 Dr. Flaherty is Professor of Medicine at Harvard and Director of the Henri and Belinda Termeer Center for Targeted Therapy at the Massachusetts General...
DREAMseq Trial: In Advanced Melanoma With BRAF Mutations, Start With Immunotherapy
In the treatment of patients with advanced melanoma containing BRAF mutations, initial treatment with an immunotherapy combination achieved superior overall survival compared with targeted therapy in the phase III DREAMseq trial, also known as the ECOG-ACRIN EA6134 trial. The results were reported ...
Research Assesses Molecular Hallmarks of Moles and Melanomas
Moles and melanomas both originate from the same type of cell—melanocytes. A study published by McNeal et al in eLife Magazine aimed to explain how common moles and melanomas form and why moles can subsequently change into melanoma. Melanocytes are cells that give color to the skin to protect it...
Impact of Time of Day of Immune Checkpoint Inhibitor Infusion on Overall Survival in Patients With Metastatic Melanoma
In a single-institution study reported in The Lancet Oncology, Qian et al found that the administration of immune checkpoint inhibitors after 4:30 PM was associated with poorer overall survival vs infusion earlier in the day in patients with metastatic melanoma. As stated by the investigators, “The ...
Immunotherapy Followed by Targeted Therapy Yields Greater Overall Survival in Patients With BRAF V600–Mutated Advanced Melanoma
Patients with BRAF V600–mutated advanced melanoma who received an immunotherapy regimen of nivolumab/ipilimumab followed by targeted therapy with dabrafenib/trametinib experienced greater overall survival (72%) compared with patients receiving the converse sequence (52%). According to the study...
CheckMate 204: Long-Term Outcomes With Nivolumab Plus Ipilimumab in Active Melanoma Brain Metastases
As reported in The Lancet Oncology by Tawbi et al, final results of the phase II CheckMate 204 trial indicate good long-term outcomes with the combination of nivolumab and ipilimumab in patients with asymptomatic active melanoma brain metastases, with poorer outcomes observed in those with...
FDA Pipeline: Novel Treatments in Lymphoma, Nasopharyngeal Cancer, Solid Tumors, and More
Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to agents for several kinds of lymphoma, as well as nasopharyngeal cancer; a Breakthrough Therapy designation for a treatment for patients with NTRK-positive advanced solid tumors; and Fast Track designation for...
Expert Point of View: Omid Hamid, MD
Commenting on the SECOMBIT trial was Omid Hamid, MD, Chief of Translational Research and Immunotherapy at The Angeles Clinic & Research Institute, a Cedars-Sinai Affiliate, and Co-Director, Cutaneous Malignancy Program, Cedars-Sinai Cancer. Dr. Hamid said SECOMBIT addresses an important...
SECOMBIT Trial Evaluates Optimal Treatment Sequencing in BRAF-Mutated Melanoma
Patients with untreated, metastatic BRAF-mutated melanoma may benefit from receiving immunotherapy first, moving to targeted therapy in the second line, data from the updated overall survival analysis of the randomized, phase II SECOMBIT trial suggest.1 The study aimed to define the optimal...
Expert Point of View: Omid Hamid, MD
“The U.S. Food and Drug Administration is currently examining pembrolizumab for the adjuvant treatment of stage IIB and IIC melanoma; if approved, we would be introducing immunotherapy earlier in the patient journey,” commented invited discussant Omid Hamid, MD (@OmidHamidMD), who was an...
Adjuvant Pembrolizumab Shows Efficacy in High-Risk Stage II Melanoma in Adults and Children Older Than 12
Adjuvant pembrolizumab reduced the risk of recurrence in adults and children older than age 12 with high-risk stage II (AJCC 8th edition, stage IIB/IIC) melanoma vs placebo, according to a late-breaking interim analysis of the phase III KEYNOTE-716 trial, presented during the European Society for...
FDA Pipeline: Recent Reviews, Designations, Applications, and Authorizations in the Oncology Space
Over the past month, the U.S. Food and Drug Administration (FDA) issued several regulatory decisions for novel treatments for patients with cancer. Priority Review for Relatlimab and Nivolumab Fixed-Dose Combination in Unresectable or Metastatic Melanoma The FDA accepted for Priority Review the...
Overall Survival With the Bispecific Fusion Protein Tebentafusp for Metastatic Uveal Melanoma
In an interim analysis of the phase III IMCgp100-202 trial reported in The New England Journal of Medicine, Nathan et al found that tebentafusp, a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector, significantly improved overall survival vs...
Adoptive Cell Therapy May Soon Be Available for Patients With Melanoma
Oncologists who treat patients with melanoma will need to become familiar with another immunotherapy approach. For refractory metastatic disease, adoptive cell therapy is on the horizon. “Adoptive cell therapy will offer additional hope for our patients with melanoma. We’ll likely be seeing this...
Adjuvant Pembrolizumab for High-Risk Stage II Melanoma: Efficacy and Safety Examined
Adjuvant pembrolizumab reduced the risk of disease recurrence in adults and children aged 12 years and older with high-risk stage II melanoma vs placebo, according to a late-breaking interim analysis of the phase III KEYNOTE-716 trial presented by Jason J. Luke, MD, and colleagues at the European...
Jason J. Luke, MD, on Melanoma: KEYNOTE-716 Trial of Pembrolizumab vs Placebo
Jason J. Luke, MD, of UPMC Hillman Cancer Center, discusses phase III results showing that adjuvant pembrolizumab for patients with resected stage IIB and IIC melanoma decreased the risk of disease recurrence or death by 35% compared with placebo. It was also associated with significantly prolonged recurrence-free survival (Abstract LBA3).
Lifileucel After Disease Progression in Metastatic Melanoma: Durable Responses Achieved in Phase II Trial
Despite the fact that we have made significant progress in metastatic melanoma with immune checkpoint inhibitors—now the standard of care—most patients experience disease progression and are left without approved treatments. There is a need for newer treatments with clinical benefit. Lifileucel, an ...
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 the time to disease progression significantly more ...
Phase II Trial Evaluates Oncolytic Coxsackievirus A21 for Unresectable Advanced Melanoma
In a phase II trial reported in the Journal of Clinical Oncology, Robert H.I. Andtbacka, MD, and colleagues found that intratumoral injection of the oncolytic RNA virus Coxsackievirus A21 (V937) was well tolerated and produced responses in some patients with unresectable stage III or stage IV...
Pembrolizumab/Entinostat for Metastatic Uveal Melanoma
In the phase II PEMDAC study, researchers showed that the combination of the PD-1 inhibitor pembrolizumab and the histone deacetylase (HDAC) inhibitor entinostat resulted in durable responses in a small group of patients with metastatic uveal melanoma. These findings were published by Ny et al in...
Are Triplets Necessary for BRAF-Mutated Melanoma?
Where does triplet therapy fit in the treatment of patients with stage IV BRAF-mutated melanoma? Is there strong evidence for combining a BRAF inhibitor, MEK inhibitor, and checkpoint inhibitor? Ragini Kudchadkar, MD, Chair of the Protocol Review and Monitoring Committee at Winship Cancer Institute ...
Patients With Melanoma Previously Treated With PD-1 or MAPK Inhibitors May Be Less Likely to Respond to ACT-TIL Therapy
Patients with metastatic melanoma who were previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) than patients naive to these treatments, according to a study...
FDA Pipeline: Reviews for Agents in Lung Cancer, Thyroid Cancer, Kidney Cancer, and More
Recently, the U.S. Food and Drug Administration (FDA) accepted applications for agents aiming to treat non–small cell lung cancer (NSCLC), differentiated thyroid cancer, renal cell carcinoma (RCC), hypersensitive acute lymphoblastic leukemia (ALL), mucosal melanoma, and endometrial carcinoma....
Topical HDAC Inhibitor Remetinostat for Basal Cell Carcinoma
A small phase II study of the topical histone deacetylase (HDAC) inhibitor remetinostat in patients with basal cell carcinoma found that the therapy was well tolerated and demonstrated clinical efficacy with no systemic side effects. The findings suggest that HDAC inhibitors are likely an effective ...
Cutaneous HPV May Be a Predictor of Cutaneous Squamous Cell Carcinoma Risk
In an article published by Rollison et al in Cancer Research, researchers demonstrated a link between the presence of cutaneous human papillomavirus (HPV) and the incidence of cutaneous squamous cell carcinomas. They also identified key characteristics of infection that may contribute to...
Pembrolizumab Shows Durable Antitumor Activity in Both Locally Advanced and Recurrent/Metastatic Squamous Cell Carcinomas
The results of the second interim analysis of the KEYNOTE-629 study of pembrolizumab in cutaneous squamous cell carcinoma confirmed durable antitumor activity in both the locally advanced and the recurrent/metastatic settings. Adverse events with pembrolizumab were generally consistent with its...
Benefits of Adjuvant Pembrolizumab in Melanoma Reinforced by EORTC 1325/KEYNOTE-054 Updates
Adjuvant anti–PD-1 antibody therapy is widely used for stage III melanoma, given the approvals of pembrolizumab and nivolumab. These approvals were based on significantly improved relapse-free survival in the CheckMate 238 trial of nivolumab compared with ipilimumab and the EORTC 1325/KEYNOTE-054...
Adjuvant Pembrolizumab Improves Distant Metastasis–Free Survival in Resected High-Risk Stage III Melanoma
As reported in The Lancet Oncology by Alexander M.M. Eggermont, MD, of Princess Máxima Center, Utrecht, the Netherlands, 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...
Interleukin-2 Pathway Agonist Bempegaldesleukin Plus Nivolumab in the First-Line Treatment of Metastatic Melanoma
In the phase II cohort of a phase I/II trial (PIVOT-02) reported in the Journal of Clinical Oncology, Adi Diab, MD, and colleagues found that the combination of the interleukin-2 pathway agonist bempegaldesleukin and nivolumab produced high response rates and extended progression-free survival in...
Study Identifies Gut Microbes Associated With Combination Immunotherapy Response and Adverse Events
Researchers have found that specific intestinal microbiota signatures may correlate with high-grade adverse events and response to combined CTLA-4 and PD-1 blockade treatment. The study, published by Andrews et al in Nature Medicine, also identified a potential new strategy to treat toxicity—while...
Expert Point of View: Jason J. Luke, MD
The invited discussant of LEAP-004, Jason J. Luke, MD, Associate Professor of Medicine and Director of the Cancer Immunotherapeutics Center, University of Pittsburgh Hillman Cancer Center, said the investigators of LEAP-0041 deserve credit for designing a study with a clearly defined...
LEAP-004 Trial Update on Lenvatinib Plus Pembrolizumab After Disease Progression in Metastatic Melanoma
Longer follow-up of the LEAP-004 trial in metastatic melanoma upheld the benefit seen with the VEGF kinase inhibitor lenvatinib plus the PD-1 inhibitor pembrolizumab for patients experiencing disease progression on prior checkpoint blockade, investigators reported at the 2021 ASCO Annual Meeting.1 ...
Registry Provides Information on Pediatric Melanoma
Pediatric melanoma is a rare disease, with only around 400 cases diagnosed in the United States every year. To better understand this disease and how best to treat it, St. Jude Children’s Research Hospital scientists created a registry called Molecular Analysis of Childhood MELanocytic Tumors...
Expert Point of View: Jason J. Luke, MD
Invited discussant of the C-144-01 study,1 Jason J. Luke, MD, Associate Professor of Medicine and Director of the Cancer Immunotherapeutics Center, University of Pittsburgh Hillman Cancer Center, Pittsburgh, noted that lifileucel is “clearly an active regimen in the post–PD-1/CTLA-4 setting and one ...
Lifileucel After Disease Progression in Metastatic Melanoma: Durable Responses Achieved in Phase II Trial
Despite the fact that we have made significant progress in metastatic melanoma with immune checkpoint inhibitors—now the standard of care—most patients experience disease progression and are left without approved treatments. There is a need for newer treatments with clinical benefit. Lifileucel, an ...
FDA Approves Expanded Indication for Pembrolizumab in Locally Advanced Cutaneous Squamous Cell Carcinoma
On July 6, the U.S. Food and Drug Administration (FDA) approved an expanded label for pembrolizumab, an anti–PD-1 agent, as monotherapy for patients with locally advanced cutaneous squamous cell carcinoma that is not curable by surgery or radiation. This approval is based on data from the second...
A Shift in the Treatment of Advanced Melanoma
Answers to questions about first-line treatment of metastatic melanoma are “going to be shifting,” Jason J. Luke, MD, told The ASCO Post, with the change coming on the heels of the phase III RELATIVITY-047 trial reported at the 2021 ASCO Annual Meeting.1 That abstract reported that using two...
Responses to Pembrolizumab and Ipilimumab After Anti–PD-1/L1 Failure in Advanced Melanoma
Despite new and effective treatments for melanoma with checkpoint inhibitors and targeted therapies, patients with metastatic melanoma who progress on frontline treatment generally do very poorly. “We really need to make sure we give these patients access to drugs that we know have some efficacy,”...
Real-World Survival Outcomes With Targeted Therapy for Intracranial Metastatic Disease
In a retrospective cohort study reported in JAMA Oncology, Erickson et al found that real-world use of targeted therapy after diagnosis of intracranial metastatic disease was associated with improved overall survival vs no use of targeted therapy in patients with HER2-positive breast cancer,...
Inclusion of Patients With Brain Metastases in Phase III Trials in Advanced Breast Cancer, Lung Cancer, and Melanoma
In a study reported in a research letter in JAMA Oncology, Corbett et al found that the majority of phase III trials investigating systemic therapy in patients with advanced lung cancer, breast cancer, and melanoma over the past 20 years have excluded or restricted enrollment of those with brain...
Omid Hamid, MD, Discusses RELATIVITY-047
Omid Hamid, MD, Chief of Translational Research/Immuno-Oncology at The Angeles Clinic & Research Institute, Los Angeles, and Co-Director of the Cutaneous Malignancy Program at Cedars-Sinai Cancer Institute, shared his thoughts on the RELATIVITY-047 study1 for The ASCO Post, referring to them as ...
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...
