Department of Dermatology, University Hospital Essen, Essen, Germany
Dirk Schadendorf , Reinhard Dummer , Axel Hauschild , Mario Santinami , Victoria Atkinson , Mario Mandalà , Vanna Chiarion-Sileni , James M.G. Larkin , Marta Nyakas , Caroline Dutriaux , Andrew Mark Haydon , Laurent Mortier , Caroline Robert , Jacob Schachter , Christine-Elke Ortmann , Egbert De Jong , Eduard Gasal , Richard Kefford , John M. Kirkwood , Georgina V. Long
Background: In the COMBI-AD trial (NCT01682083), 12 mo of adjuvant D+T led to significant improvement of RFS vs PBO (hazard ratio [HR], 0.47; P< .001) in pts with resected BRAF V600–mutant stage III melanoma; 3- and 4-year RFS rates were 59% and 54%, respectively. Previous results demonstrated consistent treatment benefit across baseline disease stage according to AJCC edition 7 or 8. Here, we further explored the association between baseline disease characteristics and RFS to identify pt subgroups likely to benefit from adjuvant treatment. Methods: Randomized pts with completely resected BRAF V600E/K–mutant stage III melanoma received 12 mo of adjuvant D (150 mg BID) + T (2 mg QD) or PBO. Within each subgroup, predictive value was explored using Kaplan-Meier analysis, and HRs were calculated using a Pike estimator. Results: Minimum follow-up was 40 mo for 870 enrolled pts (D+T, 438; PBO, 432). Kaplan-Meier analysis demonstrated treatment benefit across all subgroups analyzed. Assessment of RFS by extent of primary tumor (T stage) showed consistent benefit favoring D+T vs PBO (HR [95% CI]; T1, 0.42 [0.25-0.70]; T2, 0.51 [0.34-0.76]; T3, 0.55 [0.39-0.77]; T4, 0.42 [0.29-0.60]). HRs by nodal burden (N stage) also showed consistent treatment benefit (N1, 0.52 [95% CI, 0.37-0.72]; N2, 0.38 [95% CI, 0.28-0.53]; N3, 0.58 [95% CI, 0.41-0.83]). Substantial treatment benefit was observed in pts with baseline in-transit metastases (HR, 0.45 [95% CI, 0.24-0.82]) and those with no in-transit metastases detected at baseline (HR, 0.49 [95% CI, 0.40-0.60]). When RFS was assessed according to melanoma presentation, treatment benefit favoring D+T vs PBO was observed in pts with superficial spreading melanoma (HR, 0.48 [95% CI, 0.35-0.66]) and those with nodular melanoma (HR, 0.53 [95% CI, 0.37-0.75]). Conclusions: These results confirm earlier findings showing that treatment benefit with adjuvant D+T vs PBO is independent of baseline factors. Clinical trial information: NCT01682083
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Abstract Disclosures
2024 ASCO Annual Meeting
First Author: Axel Hauschild
2018 ASCO Annual Meeting
First Author: Reinhard Dummer
2020 ASCO Virtual Scientific Program
First Author: Axel Hauschild
2022 ASCO Annual Meeting
First Author: Dirk Schadendorf