HHE Haematology supplement 2018 - Page 18

Pending the results of ongoing, randomised controlled trials, NOACs might be considered as an alternative to LMWHs for the treatment of CAT in patients without gastrointestinal or urogenital cancer References 1 Timp JF et al. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122:1712–23. 2 Thaler J, Ay C, Pabinger I. Venous thromboembolism in cancer patients – risk scores and recent randomised controlled trials. Thromb Haemost 2012;108:1042–8. 3 Khorana AA et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013;119:648–55. 4 Ay C et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol HOKUSAI Cancer HOKUSAI Cancer was an open-label, non- inferiority trial that randomised 1050 patients with CAT to LMWH for at least five days followed by oral edoxaban 60mg once daily or dalteparin 200IU/kg daily, for one month followed by 150 IU/ kg daily during months 2–12. 18 Study drug was given for at least 6 and up to 12 months and all patients were followed for 12 months. The primary outcome was a composite of recurrent VTE or major bleeding during 12 months after randomisation and occurred in 12.8% of the patients allocated to receive edoxaban and in 13.5% of those who were randomised to dalteparin (HR 0.97; 95% CI 0.70−1.36). Recurrent VTE occurred in 7.9% of patients who were receiving edoxaban and in 11.3% of those allocated to dalteparin (difference in risk −3.4%; 95% CI −7.0−0.2). Major bleeding occurred in 6.9% of the patients in the edoxaban arm and in 4.0% of patients randomised to receive dalteparin (difference in risk 2.9%; 95% CI 0.1−5.6). Most of the difference in major bleeding was related to gastrointestinal and urogenital bleeding and the increase in the risk of major bleeding was especially high in gastrointestinal cancers. The median duration of the assigned treatment was 211 days in the edoxaban group and 184 days in the dalteparin group (p = 0.01); more patients in the dalteparin group stopped trial medication because of inconvenience of dosing. Trial medication was to be continued for at least six months. During this period, the primary outcome of recurrent VTE or major bleeding occurred in 10.5% and 10.7% in patients who were recei [™YX[[[\\[\X][H ^\][ H K NMIPH x$K K NMIHH 8$ MKܜ\ۙ[]\وԓP\H H MIHH $IJH[ LH MIHHx$NIJK\X][H  ˍ͎MIHH K$ JK NH\B\H[ܙH[X[H[][ۋ[XZ܈YY[š[H]\X[\H LNMIHHx$NIJH[[H[\\[\H NMIHH x$JK[[ IH MIHH $IJHو]Y[[H[\\[\BYZ]\XZ܈܈ۋ[XZ܈[X[BYۚYX[YY[\\\Y MH MIHBL$JHوH]Y[[H]\X[\K NBHY]KX[[\\و\HYY\ۘYY]P\H\X]Y]H\\قX\[H[U]^[۝  NŽMIHH $K JH]\H\X]Y]HY\\وXZ܈YY[  KMIHH K x$ B[HY\\و[X[H[][ۋ[XZ܂YY[[U  NMIHH x$ K MBH\[]HY\[HYX][\›وP[]Y[]U[XZ[[Z]Y H\\\ۈ]H[H\HRRHX[š\X\\[]H]Y[[YY[\BYY\Y\Yܙ\]H܈\^[]H[\[H[YY[HUX[ˈ]HB؜\][ۘ[ܝYY\\H[Z]YHHX›وY\]X]H۝ܛ\[HXو[YYYX][ۈو]Y\[\HYY\H[X[ۈX\]\[P[B^YY H\]HوX\[H]PY\Y[\H؜\][ۘ[ܝYY\Y[\Hۙ\YY[H\[Z\YX[\\[P]U[]Y[]U [YHY\[H\›YۚYX[[Z]\وHYY\˂۝\[K[[ܙX\H[HYY[\\˜Y[؜\Y[HX[[H]Y[\H[Z\YXZ]HHPˈ\H\[؜\Y]]\X[[YX[[XZ[Hۙ\YY܈XY][[\^X[[X Q[X Q\HX]K[Z\Y [X[X[\\[[\\[ UKZ[K\[H\[۝ YH MLUK™Z[K\[[۝^ N[]\X[ M[YXHZ[H܈YHYZYBYۘHZ[K܈^[۝H[ ]Y[][\[KHHX\[H]H]^[۝\ LIH MIHH $MJH܈]Y[›ۈ[\\[[ H MIHH $IJH܈]Y[›ۈ]\X[  MIHH Nx$ NJKXZ܂YY[\Y[ H MIHH $ JHوB]Y[[H[\\[[ H MIHH $LIJB[H]Y[[]Y]\X[  K ۘ\[ۜ”]\[ۙ[[Z\Y۝YX[[ؘXHY[ܙHYۈHHوPš[]Y[]U [[H\[و\BX[PZYHۜY\Y\[[\]]HU܈HX]Y[وU[]Y[]]\[\[[܈\[][[\[]H[[ܙX\YYY[\ˈPX^H[HۜY\Y\[[ۈ[]Y[\]BHZ[H[X[ۜوU[[]Y[›YYۙY[XY[[X]Y[Y\^[۝وX]Y[]U N̍΍ L8$KH[ۚH][ X\[X[X\H[XZ܈YY[\[ܘ[[XY[[\\H[]Y[]Y[\[[HHQUHY\KY[X]XH LΌM ̸$ ][ X]Y[ق[\X[X\B[]Y[][\H]ܚY]KX[[\\˜\\[YXXH[Y]Bو[XY[[ˈX\Œ MNL͎N $KYHVH][ [\\[\\[܈X]Y[وX]B[\X[X\H[]Y[]X]H[\B[Z^Y[X[X[ SPB MNM$ \ۚH][ YK[[۝[ܝ[]H]H[[X[YXܜ[]Y[][\X[X\H\\\\[܈HX]Y[و[\X]X[\X[X\K[YY L͎NM $MKM[\][ \Xܘ[[XY[[\\Y]][Z[[Yۚ\܈X]B[\X[X\N]Y[HH\H X[˂ MLNM8$KMHHH][ \Xܘ[[XY[[ PH\\›[[X[\]ZY\\[U H܈X]Y[و[\\X]YX\ U NH\[X]X]Y][Y]KB[[\\ˈX\ NX\ZN KL  N L ML MYۛܙ[H[HT˂][X][ۈو]\X[\B[]Y[][XX›X[Yۘ[Y\][XY[ZX›YYX[[\H[YKۘ\HX MΌL MMLMM ˂[[\[[HBQUHY\KX\Œ LLN8$ H\][H][ [X[\][ۈو[X[\ZY\\[܈HX]Y[و[\\[]YY\Z[X\ΈH[\BPTYK[ۘ M̎͌ $LLYۙ[H][ ܘ[\^X[܈HX]Y[وX]B[\X[X\K[YY L͎NNx$  LH[\][ ܘ[]\X[܈HX]Y[و[\X]X[[ۘ\B[X\K[YY L͍L $M˂L[X[][ XY][\\\\[[BX]Y[وX]H[\X[X\K[YY N͌N $LL[\][ YX[NH N][X[\KBM[][ ܘ[]\X[\\X][[\›[X[\ZY\\[X]Y[܈[\X[X\H[]Y[]\\\[\[[ \]ؚ[X\H[[ܙX]X˜[\[ۘ M̍ΝL $ݚM N\؈H][ YX[܈HX]Y[ق[\X\X]Y[\X[X\K[YY NMx$̍ NH[[H][ [XY[][ۈ\\H[\\\ۈو[ܘ[X܂H[X]܈][X[\ZY\\[[]Y[][\][\X[X\N\[قH[Z^YX[ SP Q K[ۘ N͎ M$̌ˈ