KEY TAKEAWAYS
- neo + adj DT is a phase II trial that compared neoadjuvant DT vs upfront surgery for BRAF-mutated melanoma, aiming to assess improved outcomes based on pCR.
- Patients received the drugs for 8 weeks before surgery and 44 weeks after surgery. Imaging was used to determine the ORR and to monitor for recurrence.
- Of 51 patients who received neoadjuvant dabrafenib and trametinib, 49 were evaluable for the primary endpoint. Radiographic ORR was 78%, including 6 CRs. Median RFS for all patients was 17.6 months and was improved for patients with pCR versus non-pCR.
- The study concluded that Neo + adj DT is safe and feasible for surgically resectable BRAF mutated melanoma.
Most melanoma patients have early-stage resectable disease. The purpose of this study was to compare the neoadjuvant plus adjuvant dabrafenib and trametinib (DT) versus upfront surgery followed by adjuvant DT in patients with surgically resectable stage III/IV BRAF mutated melanoma, aiming to assess improved outcomes based on pathologic complete response (pCR).
The study included patients with surgically resectable, measurable melanoma with BRAF V600E/K mutations. They received oral dabrafenib 150 mg twice daily and trametinib 2 mg daily for 8 weeks before surgery, and then 44 weeks of adjuvant therapy starting 1 week after surgery. Imaging was performed before surgery to determine the response rate. Neoadjuvant treatment showed a 78% radiographic overall response rate(ORR), with 6 patients achieving a complete response, 17 patients achieving a pCR, and 13 patients not responding.
Following the neo DT, 96% of patients initiated adjuvant treatment. Among them, 23 patients (47%) completed the full planned adjuvant treatment, while 7 (14%) had to discontinue due to disease recurrence, and 12 (24%) stopped due to treatment-related toxicity. The study showed that all patients’ median recurrence-free survival (RFS) was 17.6 months (95% CI: 14, 40.1). Patients who achieved a pCR had a significantly improved RFS compared to those without a pCR, with a median not reached (NR) versus 11.3 months; P= 0.0002. The median distant metastasis-free survival (DMFS) for all patients was 48.9 months (95% CI: 24.1, NA) and was better for patients with a pCR, with a median NR versus 17.5 months; P= 0.0004. The median overall survival (OS) for all patients was not reached, but it was improved in patients with a pCR (P= 0.03). No new safety concerns were observed, providing reassurance about the tolerability of the treatment. The study concluded that neoadjuvant and adjuvant DT is effective for BRAF-mutated melanoma. Patients with pCR after neo-DT have longer survival times.
Source: https://meetings.asco.org/abstracts-presentations/220200
Clinical Trial: https://clinicaltrials.gov/study/NCT02231775
Tarin Hennegan, Elizabeth M. Burton, Lauren Simpson, Victor Gerardo Prieto, Merrick I. Ross, Isabella Claudia Glitza, Lisa G Beal, Jeffrey E. Gershenwald, Hussein A. Tawbi, Michael K.K. Wong, Zhongya Wang, Roland L. Bassett, Anthony Lucci, Jeffrey Edwin Lee, Sarah B. Fisher, Sapna Pradyuman Patel, Jennifer Leigh McQuade, Michael A. Davies, Jennifer Ann Wargo, and Rodabe Navroze Amaria
Journal of Clinical Oncology 2023 41:16_suppl, 9583-9583
