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Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study.
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , |
| In: | Journal of Clinical Oncology, 35, 2017, 15_suppl, S. 9512-9512 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul |
|---|---|
| author |
Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul |
| spellingShingle |
Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul Journal of Clinical Oncology Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. Cancer Research Oncology |
| author_sort |
valpione, sara |
| spelling |
Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9512 <jats:p> 9512 </jats:p><jats:p> Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1<jats:sup>st</jats:sup> BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases. </jats:p> Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. Journal of Clinical Oncology |
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10.1200/jco.2017.35.15_suppl.9512 |
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American Society of Clinical Oncology (ASCO), 2017 |
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American Society of Clinical Oncology (ASCO), 2017 |
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1527-7755 0732-183X |
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| title |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_unstemmed |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_full |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_fullStr |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_full_unstemmed |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_short |
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_sort |
re-challenge with braf-directed treatment: a multi-institutional retrospective study. |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9512 |
| publishDate |
2017 |
| physical |
9512-9512 |
| description |
<jats:p> 9512 </jats:p><jats:p> Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1<jats:sup>st</jats:sup> BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases. </jats:p> |
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| author | Valpione, Sara, Carlino, Matteo S., Mangana, Joanna, Mooradian, Meghan, McArthur, Grant A., Schadendorf, Dirk, Hauschild, Axel, Long, Georgina V., Arance, Ana M., Ascierto, Paolo Antonio, Maio, Michele, De Rosa, Francesco, Larkin, James M. G., Park, John J., Goldinger, Simone M., Flaherty, Keith, Xu, Wen, Livingstone, Elisabeth, Weichenthal, Michael, Lorigan, Paul |
| author_facet | Valpione, Sara, Carlino, Matteo S., Mangana, Joanna, Mooradian, Meghan, McArthur, Grant A., Schadendorf, Dirk, Hauschild, Axel, Long, Georgina V., Arance, Ana M., Ascierto, Paolo Antonio, Maio, Michele, De Rosa, Francesco, Larkin, James M. G., Park, John J., Goldinger, Simone M., Flaherty, Keith, Xu, Wen, Livingstone, Elisabeth, Weichenthal, Michael, Lorigan, Paul, Valpione, Sara, Carlino, Matteo S., Mangana, Joanna, Mooradian, Meghan, McArthur, Grant A., Schadendorf, Dirk, Hauschild, Axel, Long, Georgina V., Arance, Ana M., Ascierto, Paolo Antonio, Maio, Michele, De Rosa, Francesco, Larkin, James M. G., Park, John J., Goldinger, Simone M., Flaherty, Keith, Xu, Wen, Livingstone, Elisabeth, Weichenthal, Michael, Lorigan, Paul |
| author_sort | valpione, sara |
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| description | <jats:p> 9512 </jats:p><jats:p> Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1<jats:sup>st</jats:sup> BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases. </jats:p> |
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| spelling | Valpione, Sara Carlino, Matteo S. Mangana, Joanna Mooradian, Meghan McArthur, Grant A. Schadendorf, Dirk Hauschild, Axel Long, Georgina V. Arance, Ana M. Ascierto, Paolo Antonio Maio, Michele De Rosa, Francesco Larkin, James M. G. Park, John J. Goldinger, Simone M. Flaherty, Keith Xu, Wen Livingstone, Elisabeth Weichenthal, Michael Lorigan, Paul 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9512 <jats:p> 9512 </jats:p><jats:p> Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1<jats:sup>st</jats:sup> BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases. </jats:p> Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. Journal of Clinical Oncology |
| spellingShingle | Valpione, Sara, Carlino, Matteo S., Mangana, Joanna, Mooradian, Meghan, McArthur, Grant A., Schadendorf, Dirk, Hauschild, Axel, Long, Georgina V., Arance, Ana M., Ascierto, Paolo Antonio, Maio, Michele, De Rosa, Francesco, Larkin, James M. G., Park, John J., Goldinger, Simone M., Flaherty, Keith, Xu, Wen, Livingstone, Elisabeth, Weichenthal, Michael, Lorigan, Paul, Journal of Clinical Oncology, Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study., Cancer Research, Oncology |
| title | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_full | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_fullStr | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_full_unstemmed | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_short | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| title_sort | re-challenge with braf-directed treatment: a multi-institutional retrospective study. |
| title_unstemmed | Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study. |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9512 |