First-Line and Sequencing Treatment Decisions
Dr Atkins shares his approach to first-line treatment and reviews data regarding treatment sequencing from the DREAMseq Trial.
Case: A 62-Year-Old Female with Stage IV Melanoma
- A 62-year-old female consulted with her dermatologist for removal of a pigmented lesion that had recently become darker.
- She noted that she had been experiencing persistent fatigue, shortness of breath, and a dry cough that she attributed to a prior COVID-19 infection.
- LDH: 174 UI/L
- Excisional biopsy reveals melanoma with a Breslow depth of 1.2 mm, ulcerated, mitotic rate 4/mm2
- The patient underwent wide local excision and sentinel node mapping
- Staining was positive for melanoma in the right axillary node
- CT of the chest, abdomen, and pelvis indicated multiple lesions in both lungs
- The patient underwent core-needle biopsy of the largest lung lesion, measuring 1 cm
- Pathology revealed metastatic melanoma, cutaneous nonacral with a positive BRAF V600E mutation
- ECOG PS 1
- Diagnosis: Stage IV Melanoma, T2b N1a M1b
This is a video synopsis/summary of a Case-Based Peer Perspectives episodefeaturing Michael B. Atkins, MD.
The DREAMseq trial helped determine optimal first-line therapy and sequences for BRAF-mutant metastatic melanoma. Patients were randomly assigned to nivolumab plus ipilimumab or dabrafenib plus trametinib, with crossover at progression. The primary end point was 2-year overall survival (OS).
The trial was stopped early when an interim analysis at 59% of enrollment showed a clinically meaningful difference favoring first-line immunotherapy: a 20% 2-year OS benefit over targeted therapy first. Progression-free survival, duration of response, and median OS were also improved with immunotherapy in the first line. Patients on targeted therapy without progression could cross over to immunotherapy.
Although targeted therapy responses may occur faster, combination immunotherapy also works quickly. Results of neoadjuvant trials show almost complete regional nodal response after just 6 weeks, suggesting similar response kinetics in metastases that are harder to assess radiographically.
Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.
