BRAF/MEK inhibitor rechallenge in advanced melanoma patients

被引:2
作者
Van Not, Olivier J. [1 ,2 ]
van den Eertwegh, Alfons J. M. [3 ]
Haanen, John B. [4 ]
van Rijn, Rozemarijn S. [5 ]
Aarts, Maureen J. B. [6 ]
van den Berkmortel, Franchette W. P. J. [7 ]
Blank, Christian U. [4 ,8 ]
Boers-Sonderen, Marye J. [9 ]
de Groot, Jan Willem W. B. [10 ]
Hospers, Geke A. P. [11 ]
Kapiteijn, Ellen [12 ]
Bloem, Manja [1 ,13 ,14 ]
Piersma, Djura [15 ]
Stevense-den Boer, Marion [16 ]
Verheijden, Rik J. [2 ]
van der Veldt, Astrid A. M. [17 ]
Wouters, Michel W. J. M. [1 ,13 ,14 ]
Blokx, Willeke A. M. [18 ]
Suijkerbuijk, Karijn P. M. [2 ,19 ]
机构
[1] Dutch Inst Clin Auditing, Sci Bur, Leiden, Netherlands
[2] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands
[3] VU Univ Med Ctr VUMC, Canc Ctr Amsterdam, Dept Med Oncol, Amsterdam UMC, Amsterdam, Netherlands
[4] Netherlands Canc Inst, Dept Mol Oncol & Immunol, Amsterdam, Netherlands
[5] Med Ctr Leeuwarden, Dept Internal Med, Leeuwarden, Netherlands
[6] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Med Oncol, Med Ctr, Maastricht, Netherlands
[7] Zuyderland Med Ctr Sittard, Dept Med Oncol, Sittard Geleen, Netherlands
[8] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands
[9] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, Nijmegen, Netherlands
[10] Isala Oncol Ctr, Zwolle, Netherlands
[11] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands
[12] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands
[13] Leiden Univ, Med Ctr, Dept Biomed Data Sci, Leiden, Netherlands
[14] Netherlands Canc Inst, Dept Surg Oncol, Amsterdam, Netherlands
[15] Med Spectrum Twente, Dept Internal Med, Enschede, Netherlands
[16] Amphia Hosp, Dept Internal Med, Breda, Netherlands
[17] Erasmus MC, Dept Med Oncol & Radiol & Nucl Med, Rotterdam, Netherlands
[18] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands
[19] Postbus 85500, NL-3508 GA Utrecht, Netherlands
关键词
melanoma; rechallenge; response; survival; targeted therapy; METASTATIC MELANOMA; IPILIMUMAB; RESISTANCE; COMBINATION; TRAMETINIB; NIVOLUMAB; SURVIVAL; THERAPY;
D O I
10.1002/cncr.35178
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundEffectivity of BRAF(/MEK) inhibitor rechallenge has been described in prior studies. However, structured data are largely lacking.MethodsData from all advanced melanoma patients treated with BRAFi(/MEKi) rechallenge were retrieved from the Dutch Melanoma Treatment Registry. The authors analyzed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for both first treatment and rechallenge. They performed a multivariable logistic regression and a multivariable Cox proportional hazards model to assess factors associated with response and survival.ResultsThe authors included 468 patients in the largest cohort to date who underwent at least two treatment episodes of BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS was 4.6 months (95% confidence interval [CI], 4.1-5.2), and median OS was 8.2 months (95% CI, 7.2-9.4). Median PFS after rechallenge for patients who discontinued first BRAFi(/MEKi) treatment due to progression was 3.1 months (95% CI, 2.7-4.0) versus 5.2 months (95% CI, 4.5-5.9) for patients who discontinued treatment for other reasons. Discontinuing first treatment due to progression and lactate dehydrogenase (LDH) levels greater than two times the upper limit of normal were associated with lower odds of response and worse PFS and OS. Symptomatic brain metastases were associated with worse survival, whereas a longer treatment interval between first treatment and rechallenge was associated with better survival. Responding to the first BRAFi(/MEKi) treatment was not associated with response or survival.ConclusionsThis study confirms that patients benefit from rechallenge. Elevated LDH levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit from rechallenge. A prolonged treatment interval is associated with more benefit from rechallenge. This study confirms that patients with advanced melanoma derive benefit from rechallenge with BRAFi(/MEKi). Elevated lactate dehydrogenase levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit on rechallenge.
引用
收藏
页码:1673 / 1683
页数:11
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