KEY TAKEAWAYS
- The NeoACTIVATE phase II trial aimed to assess the tolerability and efficacy of pre-TLND combination therapy in high-risk operable Stage III melanoma patients.
- The primary outcomes were PR and major PR.
- Neoadjuvant combination therapy demonstrated high PR rates in resectable Stage III melanoma patients with manageable toxicities.
Both targeted therapies and immunotherapies are effective in resected Stage III melanoma. Investigating their combined pre-therapeutic lymph node dissection(TLND) approach is crucial.
Tina J. Hieken and her team conducted a study hypothesizing that a combined targeted and immunotherapy regimen preceding TLND in resectable Stage III melanoma would be feasible and effective. Additionally, to assess pathologic responses, toxicity profiles, and peripheral blood CD8+ TCM cell expansion in the neoadjuvant setting.
Patients diagnosed with clinically evident resectable Stage III melanoma were divided into two cohorts. Cohort A (n = 15), comprising BRAF-mutated individuals, received 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab. Cohort B (n = 15), consisting of BRAF-wild-type patients, received cobimetinib and atezolizumab. Subsequently, all patients underwent TLND followed by 24 weeks of adjuvant atezolizumab.
The results demonstrated that based on the intent-to-treat analysis, it was found that 86.7% of BRAF-mutated patients achieved a pathologic response (PR) (≤50% viable tumor). In comparison, 53.3% of BRAF-wild-type patients reached the same outcome. Additionally, a major PR (defined as complete or near-complete with ≤10% viable tumor) was observed in 66.7% of BRAF-mutated patients and 33.3% of BRAF-wild-type patients. These results exceed the predefined benchmarks of 50% and 30% for major PR.
During neoadjuvant treatment, grade 3 and higher toxicities, predominantly dermatologic, occurred in 63% of patients. Notably, no instances of surgical delays or progression to regional unresectability were reported as secondary outcomes. Linked to favorable PR, an exploratory outcome indicated the expansion of peripheral blood CD8+ TCM cells.
The study showed that combining targeted and immunotherapy before lymph node surgery was well-tolerated, leading to strong pathologic responses in Stage III melanoma patients. Research was funded by Mayo Clinic.
Source: https://pubmed.ncbi.nlm.nih.gov/38365756/
Clinical Trial: https://clinicaltrials.gov/study/NCT03554083
Hieken TJ, Nelson GD, Flotte TJ, et al. (2024) ‘’Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial.’’ Nat Commun. 2024 Feb 16;15(1):1430. doi: 10.1038/s41467-024-45798-8. PMID: 38365756; PMCID: PMC10873383.
