Lu Si1, Xiaoshi Zhang2, Sang Joon Shin3, Yun Fan4, Chia-Chi Lin5, Tae Min Kim6, Arunee Dechaphunkul7, Jedzada Maneechavakajorn8, Chi Sing Wong9, Palanichamy Ilankumaran10, Dung-Yang Lee10, Eduard Gasal10, Haifu Li11, Jun Guo12. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Kidney Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: silu15_silu@126.com. 2. Sun Yat-sen University Cancer Center, Guangzhou, China. 3. Yonsei University College of Medicine, Seoul, South Korea. 4. Zhejiang Cancer Hospital, Hangzhou, China. 5. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 7. Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. 8. Rajavithi Hospital, Bangkok, Thailand. 9. Department of Clinical Oncology, Tuen Mun Hospital, Tuen Mun, New Territories, Hong Kong, China. 10. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 11. China Novartis Institutes for BioMedical Research, Beijing, China. 12. Department of Urology and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.
Abstract
PURPOSE: This study (NCT02083354) assessed the efficacy and safety of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma. METHOD: Overall, 77 patients of East Asian origin (including 61 from Mainland China) with unresectable or metastatic BRAF V600-mutant cutaneous melanoma were enrolled. Prior treatment was allowed except with BRAF/MEK inhibitors. Patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end-point was objective response rate (ORR) using Response Evaluation Criteria in Solid Tumours 1.1. Secondary end-points were duration of response (DOR), progression-free survival (PFS), overall survival (OS), pharmacokinetics and safety. RESULTS: At data cutoff (February 23, 2018; median follow-up, 8.3 months), treatment was ongoing in 36 patients (47%). The median age was 52 years; 32% of patients had elevated lactate dehydrogenase, and 84% had received prior systemic therapy. ORR was 61% (95% confidence interval: 49.2-72.0), with four patients (5%) achieving complete response. Median DOR and PFS were 11.3 and 7.9 months, respectively. Median OS was not reached. The most common adverse event (AE) of any grade was pyrexia (56%). Grade ≥III AEs occurred in 29 patients (38%). The most common grade ≥III AEs were pyrexia (8%) and anaemia (6%). AEs led to permanent discontinuation in five patients (6.5%). Mean Cmax for dabrafenib and trametinib was 3560 and 11.5 ng/mL (day 1) and 2680 and 27.1 ng/mL (day 15), respectively. CONCLUSION: These results support the efficacy and tolerability of dabrafenib in combination with trametinib in East Asian patients with unresectable or metastatic BRAF V600-mutant cutaneous melanoma.
PURPOSE: This study (NCT02083354) assessed the efficacy and safety of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma. METHOD: Overall, 77 patients of East Asian origin (including 61 from Mainland China) with unresectable or metastatic BRAF V600-mutant cutaneous melanoma were enrolled. Prior treatment was allowed except with BRAF/MEK inhibitors. Patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end-point was objective response rate (ORR) using Response Evaluation Criteria in Solid Tumours 1.1. Secondary end-points were duration of response (DOR), progression-free survival (PFS), overall survival (OS), pharmacokinetics and safety. RESULTS: At data cutoff (February 23, 2018; median follow-up, 8.3 months), treatment was ongoing in 36 patients (47%). The median age was 52 years; 32% of patients had elevated lactate dehydrogenase, and 84% had received prior systemic therapy. ORR was 61% (95% confidence interval: 49.2-72.0), with four patients (5%) achieving complete response. Median DOR and PFS were 11.3 and 7.9 months, respectively. Median OS was not reached. The most common adverse event (AE) of any grade was pyrexia (56%). Grade ≥III AEs occurred in 29 patients (38%). The most common grade ≥III AEs were pyrexia (8%) and anaemia (6%). AEs led to permanent discontinuation in five patients (6.5%). Mean Cmax for dabrafenib and trametinib was 3560 and 11.5 ng/mL (day 1) and 2680 and 27.1 ng/mL (day 15), respectively. CONCLUSION: These results support the efficacy and tolerability of dabrafenib in combination with trametinib in East Asian patients with unresectable or metastatic BRAF V600-mutant cutaneous melanoma.