Dr Long on Unmet Needs in BRAF-Mutant Melanoma

Georgina V. Long, MBBS, PhD, FRACP, co-medical director, Melanoma Institute Australia (MIA), and chair, Melanoma Medical Oncology and Translational Research, MIA and Royal North Shore Hospital, The University of Sydney, discusses the remaining unmet needs for patients with 

-mutant melanoma and how data from the phase 3 NADINA trial (NCT04949113) could help address some of these needs.

Despite advancements in adjuvant and metastatic treatment settings, significant challenges remain for patients with 

-mutant melanoma, Long notes. She explains that more than half of patients who receive adjuvant combination therapy with dabrafenib (Tafinlar) and trametinib (Trametinib) experience recurrence. Additionally, approximately half of patients with metastatic 

-mutated melanoma will ultimately die of their disease, Long continues. These statistics underscore the critical need for improved therapeutic strategies for this patient population, Long says.

Findings from the NADINA trial were presented by Christian U. Blank, MD, PhD, of the Netherlands Cancer Institute at the 

. The trial investigated the efficacy of neoadjuvant combination therapy with nivolumab (Opdivo) plus ipilimumab (Yervoy), followed by adjuvant nivolumab with or without radiotherapy, compared with adjuvant nivolumab with or without radiotherapy in patients with stage III de novo or recurrent resectable melanoma with a least 1 lymph node metastasis. Notably, the trial enrolled patients with 

Data showed that patients in the experimental arm (n = 212) experienced a 68% reduction in the risk of recurrence, progression, or death vs those in the control arm (HR, 0.32; 99.9% CI, 0.15-0.66; 

< .0001). The 1-year event-free survival (EFS) rates were 83.7% for the neoadjuvant arm vs 57.2% for the adjuvant arm.

-mutated melanoma, the risk of recurrence, progression, or death was reduced by 71% for the neoadjuvant regimen vs the adjuvant regimen (HR, 0.29; 99.9% CI, 0.11-0.79; 

-mutated disease treated in the neoadjuvant setting (n = 112) experienced a 1-year EFS rate of 83.5% vs 52.2% for those treated in the adjuvant setting alone (n = 112).

Videos

Georgina Long, MBBS, PhD, FRACP, discusses unmet needs for BRAF-mutant melanoma, highlighting key insights from the phase 3 NADINA trial.

Georgina Long, BSc, PhD, MBBS, FRACP, co-medical director, Melanoma Institute Australia (MIA), chair of Melanoma Medical Oncology and Translational Research, MIA and Royal North Shore Hospital, University of Sydney, discusses the rationale for the phase 3 COMBI-i trial in 

The COMBI-i study evaluated the combination of spartalizumab, dabrafenib ​(Tafinlar), and trametinib ​(Mekinist), says Long. Findings from parts 1 and 2 of the phase 3 trial were presented during the 

 and showed encouraging clinical activity and tolerability with the novel triplet. 

When using a BRAF inhibitor in combination with a MEK inhibitor, patient biopsies ​often show an influx of T cells within the first week of treatment​, Long explains.

Ultimately, this was the rationale behind the study, ​as the field wanted to determine whether the addition of immunotherapy would induce prolonged, durable responses in this patient population, Long concludes.

Georgina Long, BSc, PhD, MBBS, FRACP, discusses the rationale for the phase 3 COMBI-i trial in BRAF V600­–mutant melanoma.








Dr. Long on the Rationale for the Phase 3 COMBI-i Trial in BRAF V600¬–Mutant Melanoma 

Georgina Long, BSc, PhD, MBBS, FRACP, medical oncologist, translational researcher, Melanoma Institute Australia, The University of Sydney, discusses which patients may benefit from the combination of dabrafenib and trametinib based on several recent clinical trials.

The FDA just granted a full approval of dabrafenib and trametinib for patients with unresectable or metastatic BRAF-mutated melanoma.

Lactic dehydrogenase (LDH) drives which patients will benefit from the combination of dabrafenib and trametinib, says Long. The number of disease sites a patient has is also relevant, says Long. Out of the 617 patients that received this combiantion, about one-third had normal LDH at baseline and less than three disease sites. These patients had a three-year survival of about 70%, says Long.

Another interesting observation was that different patients progressed on the combination at different rates, says Long. Those who tend to progress quickly tend to develop new brain metastasis or growth in new and existing sites.

Georgina Long, BSc, PhD, MBBS, FRACP, medical oncologist, translational researcher, Melanoma Institute Australia, The University of Sydney, discusses which patients may benefit from the combination of dabrafenib and trametinib based on several recent clinical trials.


Georgina Long, BSc, PhD, MBBS, FRACP

Articles

Dr Long on Unmet Needs in BRAF-Mutant Melanoma

Dr. Long on the Rationale for the Phase 3 COMBI-i Trial in BRAF V600¬–Mutant Melanoma

Dr. Georgina Long on Dabrafenib and Trametinib in BRAF-Mutated Melanoma