| 标题 |
Real life targeted therapies alone or in combination in brain metastases patients: French experience within MelBase
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| 其它 | Melanoma brain metastases (BM) result in poor prognosis. Targeted therapies (TT) showed significant efficacy in monotherapy (Vemurafenib V/Dabrafenib D) and in combination (V+Cobimetinib VC/D+Trametinib DT). Encouraging data from BM treated by TT com-bination were reported. We present original results of efficacy and tol-erance in real life BM treated with TT (V/D, VC/DT) in French MelBase. It is a multicentric clinical biobank dedicated to prospective follow-up (FU) of unresectable stage III or IV melanoma adults. 1168 patients are included. Available data were collected (June 2017) and analyzed: monotherapy (gA), combination (gB). The characteristics are: gA (n = 58): mean age 58 years (48-70), PS 0-1 81%, LDH>ULN 36%, ≥3 metastatic organ sites (MOS) 60%, treated in 1st line 67%. gB (n = 64): mean age 56 years (45-64), PS 0-1 90%, LDH>ULN 39%, ≥3 MOS 63%, treated in 1st line 70%. After median FU 7.3 months (mos), median OS is 8.3 mos (95% CI:6.8-11.8;gA), 15.1 months (95% CI:7.7-NR;gB); median PFS is 4.0 mos (95% CI:3.5-5.6;gA), 6.6 mos (95% CI:5.5-8.1;gB). BORR is 31% (gA), 41% (gB); DCR is 64% (gA;gB). Age, LDH, PS, BM, radiotherapy (RT) were tested in univariate analysis. Multivariate analysis on global population (with treatment stratification) indicates that LDH (adjusted HR 1.9, 95% CI: 1.2-3.3), PS (aHR 3.6, 95% CI: 1.9-6.8), RT (aHR 2.3, 95% CI: 1.3-4.2) are significantly associated with OS; PS (aHR 3.0, 95% CI: 1.6-5.5), BM (aHR 1.5, 95% CI: 1.0-2.4) are significantly associated with PFS. OS and PFS seem similar to already published data (Davies 2017) in both groups. Adding anti-MEK increases BORR but not DCR. It increases PFS and OS but less than in patients without BM. It is the 1st study evaluating prognostic factors and pointing out RT as a good factor in multivariate analysis. Concomitant stereotaxic RT should systematically be discussed in BM patients treated by TT. |
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