Περίληψη:
Aim Understanding predictors of long-term benefit with currently available melanoma therapies is the key for optimising individualised treatments. A prior pooled analysis of dabrafenib plus trametinib (D + T)–randomised trials (median follow-up, 20.0 months) identified baseline lactate dehydrogenase (LDH) and number of organ sites with metastasis as predictive factors for progression-free (PFS) and overall (OS) survival. However, longer-term follow-up analyses are needed to confirm which patients treated with D + T can achieve maximum benefit. Methods Three-year landmark data were retrospectively pooled for D + T patients in phase 3 trials (COMBI-d [NCT01584648]; COMBI-v [NCT01597908]). Univariate and multivariate analyses assessed prognostic values of predefined baseline factors; regression tree analysis determined hierarchy and interactions between variables. Results Long-term pooled outcomes were consistent with individual trial results (N = 563; 3-year PFS, 23%; 3-year OS, 44%). Baseline LDH level and number of organ sites remained strongly associated with and/or predictive of PFS and OS. In addition, baseline sum of lesion diameters (SLD) was identified as a predictor for progression. In the most favourable prognostic group (normal LDH, SLD <66 mm, <3 organ sites; n = 183/563 [33%]), 3-year PFS was 42%. Baseline number of organ sites was also predictive of outcomes in patients with PFS ≥ 6 months. Conclusion Using the largest phase 3 data set available for BRAF/MEK inhibitor combination therapy in melanoma, these results demonstrate that durable responses lasting ≥3 years are possible in subsets of patients with BRAF-mutant melanoma receiving D + T. Although the best predictive model evolved with longer follow-up, factors predicting clinical outcomes with the combination remained consistent with previous analyses. © 2017 Elsevier Ltd
Συγγραφείς:
Schadendorf, D.
Long, G.V.
Stroiakovski, D.
Karaszewska, B.
Hauschild, A.
Levchenko, E.
Chiarion-Sileni, V.
Schachter, J.
Garbe, C.
Dutriaux, C.
Gogas, H.
Mandalà, M.
Haanen, J.B.A.G.
Lebbé, C.
Mackiewicz, A.
Rutkowski, P.
Grob, J.-J.
Nathan, P.
Ribas, A.
Davies, M.A.
Zhang, Y.
Kaper, M.
Mookerjee, B.
Legos, J.J.
Flaherty, K.T.
Robert, C.
Λέξεις-κλειδιά:
dabrafenib; lactate dehydrogenase; trametinib; antineoplastic agent; dabrafenib; imidazole derivative; lactate dehydrogenase; oxime; protein kinase inhibitor; pyridone derivative; pyrimidinone derivative; trametinib, Article; cancer survival; clinical outcome; follow up; human; intention to treat analysis; metastatic melanoma; overall survival; phase 3 clinical trial (topic); prediction; priority journal; progression free survival; randomized controlled trial (topic); retrospective study; treatment duration; adult; aged; clinical trial; controlled study; female; male; melanoma; metabolism; metastasis; middle aged; pathology; phase 3 clinical trial; predictive value; prognosis; randomized controlled trial; risk factor; survival analysis, Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Imidazoles; L-Lactate Dehydrogenase; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Oximes; Predictive Value of Tests; Prognosis; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Risk Factors; Survival Analysis
