Melanoma & Skin Cancer

The panel explains which BRAF/MEK inhibitor combination therapy they each tend to turn to when treating a patient with BRAF-mutated metastatic melanoma.

Key opinion leaders explain that clinicians should warn patients with BRAF-mutated metastatic melanoma starting BRAF/MEK inhibitor therapy about short-term toxicities like fever, chills, and rash that can differ greatly from immunotherapy toxicities.

Experts discuss a preference for ipilimumab/nivolumab as the frontline immunotherapy for patients with BRAF-mutant metastatic melanoma given its proven long-term efficacy but acknowledge nivolumab/relatlimab as an option with less toxicity, especially adrenal insufficiency.

Beyond symptoms, doctors consider the psychosocial factors impacting treatment access and adherence, like insurance coverage, cost, family support, and preexisting conditions, when deciding between immunotherapy and targeted therapy for patients with BRAF-mutated metastatic melanoma.

The FDA has granted clearance for an investigational new drug application for a phase 1/2 safety lead-in trial investigating the engineered tumor-infiltrating lymphocyte KSQ-001EX in patients with melanoma, head and neck squamous cell carcinoma, and non–small cell lung cancer.

Paul D. Nathan, MBBS, PhD, FRCP, discusses the design of the phase 3 IMCgp100-202 trial of tebentafusp-tebn in patients with previously untreated, HLA-A*02:01–positive metastatic uveal melanoma, highlighting the key enrollment criteria of the randomized, open-label study.

Paul D. Nathan, MBBS, PhD, FRCP, discusses the rationale for launching the phase 3 IMCgp100-202 trial evaluating tebentafus in patients with previously untreated, HLA-A*02:01–positive metastatic uveal melanoma, as well as the mechanism of action of the agent.

Jeffrey S. Weber, MD, PhD, discusses the use of circulating-tumor DNA dynamics when guiding treatment decision-making in melanoma, according to data from the phase 2b mRNA-4157-P201/KEYNOTE-942 trial.

Omid Hamid, MD, director, Melanoma Program, The Angeles Clinic and Research Institute, Cedars-Sinai, discusses the rationale for a phase 1 trial of fianlimab plus cemiplimab in patients with advanced melanoma who have received prior adjuvant PD-1 inhibitors.

Elizabeth Buchbinder, MD, discusses the investigation of treatment with nivolumab maintenance therapy in patients with melanoma who experienced severe immune-related adverse effects associated with combination therapy with nivolumab and ipilimumab.

For patients with BRAF-mutant metastatic melanoma, doctors assess symptoms and disease status to determine if they should start treatment with combination immunotherapy, or 8-12 weeks of BRAF/MEK targeted therapy before switching to immunotherapy, which offers the possibility of durable responses or cure.

The panelists emphasize the importance of obtaining tissue for BRAF-mutation testing and dedicated tissue tracking in patients with metastatic melanoma, with immunohistochemistry followed by confirmatory next-generation sequencing, and discuss the promise of liquid biopsies like ctDNA as a future biomarker tracking modality.

The addition of bemcentinib to the standard-of-care therapies of pembrolizumab or dabrafenib plus trametinib was well tolerated in patients with metastatic melanoma; however, it did not lead to improvements in overall response rate, progression-free survival, or overall survival vs SOC alone.

Paul Nathan, MBBS, PhD, MRCP, discusses the differences between cutaneous melanoma and uveal melanoma that have led to unique unmet needs for patients with the latter malignancy; updated findings from the IMCgp100-202 trial; and how these findings may influence future clinical practice.

When a patient with metastatic melanoma patient tests negative for the BRAF V600E mutation, doctors recommend sending the sample for next-generation sequencing testing which can take 2-3 weeks, during which time they may start immunotherapy if the patient has aggressive disease, but ideally should wait for results to guide treatment.

Expert panelists stress the importance of biomarker testing for BRAF mutations to guide treatment options when a patient is diagnosed with metastatic melanoma.

Treatment with the novel immunotherapy PV-10 led to hepatic responses in patients with metastatic uveal melanoma with liver metastases, according to updated data from a phase 1 trial.

Paul D. Nathan, MBBS, PhD, FRCP, discusses the 3-year survival data from the phase 3 IMCgp100-202 trial of tebentafusp-tebn in patients with previously untreated, HLA-A*02:01–positive metastatic uveal melanoma.

Ze'ev Ronai, PhD, discusses key advancements in the treatment of patients with melanoma, including the discovery of NRAS and BRAF mutations, as well as the development of immunotherapy approaches.

Dr Weber discusses the FDA approval of adjuvant nivolumab for patients with completely resected stage IIB/C melanoma, key efficacy data from the CheckMate76K trial, and potential future directions for PD-1 inhibitor–based combinations in the melanoma treatment paradigm.

Elizabeth I. Buchbinder, MD, discusses findings from a retrospective study evaluating the resumption of nivolumab maintenance therapy in patients with advanced melanoma who discontinued treatment with the combination of nivolumab and ipilimumab due to immune-related adverse effects.

Jeffrey S. Weber, MD, PhD, discusses findings from the phase 2b mRNA-4157-P201/KEYNOTE-942 trial of mRNA-4157 in combination with pembrolizumab in resected high-risk melanoma.

Neil D. Gross, MD, FACS, discusses 1-year follow-up data from a phase 2 study of neoadjuvant cemiplimab in cutaneous squamous cell carcinoma.

Meredith McKean, MD, MPH, discusses the efficacy and safety of treatment with the anti-TGIT agent etigilimab and the PD-1 inhibitor nivolumab in patients with solid tumors and PD-L1-low disease.

Danielle K. DePalo, MD, explains the lack of research directly comparing first-line treatment options for patients with unresectable melanoma in-transit metastases, expands on the safety and efficacy of 3 treatment modalities for these patients, and underscores the need for more data to inform the management of these patients.