Inter- and Intra-Patient Heterogeneity of Response and Progression to Targeted Therapy in Metastatic Melanoma.
In: PLoS ONE, Jg. 9 (2014), Heft 1, S. 1-9
Online
academicJournal
Zugriff:
Background: MAPK inhibitors (MAPKi) are active in BRAF-mutant metastatic melanoma patients, but the extent of response and progression-free survival (PFS) is variable, and complete responses are rare. We sought to examine the patterns of response and progression in patients treated with targeted therapy. Methods: MAPKi-naïve patients treated with combined dabrafenib and trametinib had all metastases ≥5 mm (lymph nodes ≥15 mm in short axis) visible on computed tomography measured at baseline and throughout treatment. Results: 24 patients had 135 measured metastases (median 4.5/patient, median diameter 16 mm). Time to best response (median 5.5 mo, range 1.7–20.1 mo), and the degree of best response (median −70%, range +9 to −100%) varied amongst patients. 17% of patients achieved complete response (CR), whereas 53% of metastases underwent CR, including 42% ≥10 mm. Metastases that underwent CR were smaller than non-CR metastases (median 11 vs 20 mm, P<0.001). PFS was variable among patients (median 8.2 mo, range 2.6–18.3 mo), and 50% of patients had disease progression in new metastases only. Only 1% (1/71) of CR-metastases subsequently progressed. Twelve-month overall survival was poorer in those with a more heterogeneous initial response to therapy than less heterogeneous (67% vs 93%, P = 0.009). Conclusion: Melanoma response and progression with MAPKi displays marked inter- and intra-patient heterogeneity. Most metastases undergo complete response, yet only a small proportion of patients achieve an overall complete response. Similarly, disease progression often occurs only in a subset of the tumor burden, and often in new metastases alone. Clinical heterogeneity, likely reflecting molecular heterogeneity, remains a barrier to the effective treatment of melanoma patients. [ABSTRACT FROM AUTHOR]
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Titel: |
Inter- and Intra-Patient Heterogeneity of Response and Progression to Targeted Therapy in Metastatic Melanoma.
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Autor/in / Beteiligte Person: | Menzies, Alexander M. ; Haydu, Lauren E. ; Carlino, Matteo S. ; Azer, Mary W. F. ; Carr, Peter J. A. ; Kefford, Richard F. ; Long, Georgina V. |
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Zeitschrift: | PLoS ONE, Jg. 9 (2014), Heft 1, S. 1-9 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0085004 |
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