دواء لعلاج الأورام مع تغيير جيني محدد . Vitrakvi (larotrectinib) للبالغين والأطفال الذين يعانون من أورام صلبة تُختَبر إيجابية لجينات NTRK

1. Vitrakvi (larotrectinib)
Dr. Firas KassabPage1
( ‫األٍشٝنٞخ‬ ‫ٗاىذٗاء‬ ‫اىغزاء‬ ‫إداسح‬ ‫ٗافقذ‬FDA‫اىْظش‬ ‫ثغط‬ ‫ٍسذد‬ ْٜٞ‫خ‬ ‫رغٞٞش‬ ‫ٍغ‬ ً‫األٗسا‬ ‫ىؼالج‬ ‫دٗاء‬ ٚ‫ػي‬ )
.ُ‫اىغشغب‬ ‫ّ٘ع‬ ِ‫ػ‬Vitrakvi (larotrectinib)ِٞ‫ىيجبىغ‬‫جش‬َ‫ز‬‫خ‬ُ‫ر‬ ‫صيجخ‬ ً‫أٗسا‬ ٍِ ُّ٘‫ٝؼب‬ ِٝ‫اىز‬ ‫ٗاألغفبه‬
‫ىدْٞبد‬ ‫إٝدبثٞخ‬NTRK‫ٍؼشٗفخ‬ ‫ٍقبٍٗخ‬ ‫غفشح‬ ‫ٗخ٘د‬ ُٗ‫د‬ ‫ػصجٞخ‬ ‫ىَغزقجالد‬ ‫مْٞبص‬ ِٝ‫رٞشٗص‬ٗ ،ٜ‫اىز‬
‫شبئؼخ‬ ‫ىٞغذ‬ ْٜٞ‫اىد‬ ‫اىزغٞش‬ ٍِ ‫اىْ٘ع‬ ‫ٕزا‬ ‫ٍغ‬ ً‫األٗسا‬ .‫اىغشغبّٞخ‬ ً‫األٗسا‬ َّ٘ ٚ‫ػي‬ ‫رغبػذ‬ ُ‫أ‬ ِ‫َٝن‬
ِ‫َٝن‬ ِ‫ٗىن‬‫ٍشبٕذرٖب‬‫اىغ‬ ‫عشغبّبد‬ ٜ‫ف‬.‫اىشخ٘ح‬ ‫األّغدخ‬ ‫ٗعبسمٍ٘ب‬ ‫ٗاىشئخ‬ ‫اىذسقٞخ‬ ‫ٗاىغذح‬ ‫اىيؼبثٞخ‬ ‫ذح‬
‫اىؼالخبد‬ ‫خاله‬ ‫َّذ‬ ٜ‫ٗاىز‬ ‫خشازٞب‬ ‫اعزئصبىٖب‬ ِ‫َٝن‬ ‫ال‬ ٗ‫أ‬ ‫اّزششد‬ ٜ‫اىز‬ ً‫األٗسا‬ ‫ىؼالج‬ ‫اىذٗاء‬ ً‫ٝغزخذ‬
.‫اىغبثقخ‬
‫اىخصبئص‬ ‫أعبط‬ ٚ‫ػي‬ ً‫األٗسا‬ ‫رؼبىح‬ ٜ‫اىز‬ ُ‫اىغشغب‬ ‫ػقبقٞش‬ ‫رط٘ٝش‬ ٜ‫ف‬ ‫ٍَٖخ‬ ‫خط٘ح‬ ٜٕ ‫اىَ٘افقخ‬ ٓ‫ٕز‬
‫ى‬ ‫اى٘ساثٞخ‬ٌ‫اىدغ‬ ٜ‫ف‬ ‫ٍ٘قؼٖب‬ ‫ٗىٞظ‬ ، ً‫ي٘س‬) ‫اىذٗاء‬ ‫ٕزا‬ ‫َٝٞض‬ ‫ٍب‬ ٕ٘ ٗ (.
‫األٍشٝنٞخ‬ ‫ٗاىذٗاء‬ ‫اىغزاء‬ ‫إداسح‬ ‫قبٍذ‬ ،(FDA)ٜ‫اىَبظ‬ ً‫اىؼب‬ ٜ‫ف‬ٚ‫ػي‬ ‫اىَ٘افقخ‬ ‫ثز٘عٞغ‬Keytruda
(pembrolizumab)‫ٍزقذ‬ ‫صيجخ‬ ً‫ثأٗسا‬ ِٞ‫اىَصبث‬ ‫ٗاألغفبه‬ ِٞ‫ىيجبىغ‬ ‫اىؼالج‬ َِ‫ىززع‬‫ٍغز٘ٝبد‬ ‫راد‬ ‫ٍخ‬
‫اإل‬ ً‫ػذ‬ ٍِ ‫ػبىٞخ‬‫اىصغشٝخ‬ ‫اىغ٘ارو‬ ٜ‫ف‬ ‫عزقشاس‬(MSI-H)ٗ‫أ‬(dMMR)‫اىز٘افق‬ ً‫ػذ‬ ‫إصالذ‬ ‫ػ٘ص‬
mismatch repair deficient.
ٚ‫ػي‬ ‫ٍ٘افقزٖب‬ ‫ٗاىؼقبقٞش‬ ‫األغزٝخ‬ ‫إداسح‬ ‫اػزَذد‬3‫شَيذ‬ ‫عشٝشٝخ‬ ‫ردبسة‬55‫ٗاألغفبه‬ ِٞ‫اىجبىغ‬ ٍِ
‫ث‬ ُ٘‫اىَصبث‬ٗ ، ُ‫اىغشغب‬ ٍِ ‫ٍخزيفخ‬ ‫أّ٘اع‬ ‫ؼذح‬ً‫أٗسا‬ ٍِ ُّ٘‫ٝؼب‬ ٌٖ‫خَٞؼ‬NTRK‫إٝدب‬‫ثٞخ‬ٍِٗ‫اىَشخر‬
ُ‫أ‬ٛ‫ٝؤد‬‫االعزئصبه‬ٜ‫اىدشاز‬ٚ‫إى‬‫ظشس‬‫شذٝذ‬،ٗ‫أ‬ٜ‫ف‬‫زبه‬ً‫ػذ‬‫ر٘فش‬‫ػالخبد‬‫ثذٝيخ‬‫شظٞخ‬ٍُٗ‫أ‬ٜ‫ف‬
‫زبالد‬ً‫ػذ‬ِ‫اىزسغ‬‫ثؼذ‬‫اىؼالج‬

2. Vitrakvi (larotrectinib)
Dr. Firas KassabPage2
ٚ‫اىَشظ‬ ‫خَٞغ‬ ٜ‫أػط‬‫دٗاء‬Vitrakviٛ‫ٗاىز‬ ،ٜٝ‫اىني‬ ‫االعزدبثخ‬ ‫ٍؼذه‬ ُ‫ٗمب‬ . ‫زج٘ة‬ ‫شنو‬ ٜ‫ف‬ ٜ‫أر‬(ٗ
ً‫األٗسا‬ ‫رقيصذ‬ ِٝ‫اىز‬ ٚ‫اىَشظ‬ ٍِ ‫خضء‬ ٕ٘) ٌٖٝ‫ىذ‬،75٪‫(ٍؼذه‬‫إ‬‫مبٍو‬ ‫عزدبثخ‬22ٗ ٪‫ٍؼذه‬‫إ‬‫عزدبثخ‬
ٜ‫خضئ‬53. ) ً‫األٗسا‬ ٍِ ‫ٍخزيفخ‬ ‫أّ٘اع‬ ‫ػجش‬ ٪‫إ‬‫ىَذح‬ ِ‫اىزسغ‬ ‫عزَش‬6ٜ‫ف‬ ‫األقو‬ ٚ‫ػي‬ ‫أشٖش‬73، ٪
ٜ‫ف‬ ‫األقو‬ ٚ‫ػي‬ ‫عْخ‬ ‫ٗىَذح‬39. ‫ىيؼالج‬ ‫اعزدبث٘ا‬ ِٝ‫اىز‬ ٍِ ٪
ٚ‫ػي‬ ‫اىَ٘افقخ‬ ‫رَذ‬Vitrakvi‫ٍْبٕح‬ ٍِ ‫اىؼذٝذ‬ ً‫ثبعزخذا‬FDA‫ىؼالج‬ ‫األدٗٝخ‬ ‫ر٘افش‬ ‫ىزغشٝغ‬ ‫اىَصََخ‬
ٌ‫ر‬ ‫مَب‬ . ‫اىخطٞشح‬ ‫األٍشاض‬ٔ‫ٍْس‬( ‫اىٞزَٞخ‬ ‫األدٗٝخ‬ ‫رغَٞخ‬orphan drug‫ٍبىٞخ‬ ‫ز٘افض‬ ‫ر٘فش‬ ٜ‫ٗاىز‬ ، )
.‫اىْبدسح‬ ‫ىألٍشاض‬ ‫األدٗٝخ‬ ‫رط٘ٝش‬ ‫ىزشدٞغ‬
‫رغ٘ٝق‬ ٌ‫ٝز‬Vitravki‫ث٘اعطخ‬BayerٗLoxo Oncology،Inc.
( ‫ٝؼزجش‬Vitrakvi (larotrectinibّٔ٘‫م‬ ‫ثغجت‬ ‫ٍَٞضا‬:
)*‫ثَؤشش‬ ‫ػالج‬ ‫أٗه‬‫عشٝغ‬ ٍٜ‫ٗس‬‫األٗىٞخ‬ ‫ٗاألدٗٝخ‬ ‫األغزٝخ‬ ‫إداسح‬ ‫ٍ٘افقخ‬ ‫ٗقذ‬ ٜ‫ف‬ٔٞ‫ػي‬
)*75٪‫ٍؼذه‬‫اإل‬‫عزدبثخ‬‫اى‬ٞ‫ني‬‫خ‬95 (ORR)٪CI،61، ٪85٪(ٗ‫األ‬ ‫ٍخزيف‬ ‫ػجش‬ِٞ‫اىجبىغ‬ ‫ػْذ‬ ‫اىصيجخ‬ ً‫سا‬
‫ٗاألغفب‬‫ه‬.
‫إداسح‬ ‫ٍ٘افقخ‬ ُ‫إ‬ٚ‫ػي‬ ‫ٗاىؼقبقٞش‬ ‫األغزٝخ‬larotrectinib‫َٝثو‬‫عبثقخ‬ٛ‫اىز‬ ُ‫اىغشغب‬ ‫ػالج‬ ‫مٞفٞخ‬ ٜ‫ف‬
ٚ‫ػي‬ ٛ٘‫ٝسز‬ْٜٞ‫اىد‬ ‫اإلّذٍبج‬NTRK(ُ‫اىغشغب‬ ٍِ ‫ّبدس‬ ‫ٍسشك‬ ٕ٘).
‫ىقذ‬٘‫ى‬ً‫ثبعزخذا‬ ‫ىيؼالج‬ ِ‫َٝن‬ ‫مٞف‬ ‫ٍجبشش‬ ‫ثشنو‬ ‫زظذ‬larotrectinibٗ ،‫ب‬ً‫ص‬ٞ‫خص‬ ََٔٞ‫رص‬ ٌ‫ر‬ ٛ‫اىز‬
‫اى‬ ‫ىٖزا‬‫َسفض‬،ًٗ‫ٝقذ‬‫إ‬‫عزدبثبد‬‫عش‬‫فؼبىخ‬ ‫ٝشٝخ‬ٙ‫ىذ‬ُ‫عشغب‬ ٍِ ُّ٘‫ٝؼب‬ ِٝ‫اىز‬ ٚ‫اىَشظ‬‫إ‬‫ّذٍبج‬TRK،
‫األدٗٝخ‬ ٌ‫قغ‬ ‫سئٞظ‬ ، ٛ‫ثشش‬ ‫غجٞت‬ ، ُ‫َٕٞب‬ ‫دٝفٞذ‬ ‫قبه‬ ،" ً‫اى٘س‬ ‫ّ٘ع‬ ٗ‫أ‬ ‫اىَشٝط‬ ‫ػَش‬ ِ‫ػ‬ ‫اىْظش‬ ‫ثغط‬
ٗ ، ُ‫ىيغشغب‬ ‫مٞزٞشْٝغ‬ ُ٘‫عي‬ ‫ٍَٞ٘لاير‬ ‫ٍشمض‬ ٜ‫ف‬ ‫اىزط٘ٝش‬ ‫خذٍخ‬ ‫اىَجنشح‬‫إلخشاء‬ ٜ‫سئٞغ‬ َٜ‫ػبى‬ ‫ٍسقق‬
‫خاله‬ ٍِ ‫عشٝشٝخ‬ ‫ردشثخ‬‫اىْظش‬ ‫ثغط‬ ، ْٜٞ‫اىد‬ ‫اىزغٞٞش‬ ‫ىٖزا‬ ‫ٍؼزَذ‬ ‫ػالج‬ ‫أٗه‬ ُٟ‫ا‬ ‫"ىذْٝب‬ .ٛ‫اىغشٝش‬ ‫اىؼالج‬
ُ‫اىغشغب‬ ‫ّ٘ع‬ ِ‫ػ‬".
ِٞ‫اىد‬ ‫اّذٍبخبد‬ ُ‫إ‬NTRK‫رغٞش‬ ٜٕ‫ثشٗرْٞبد‬ ٚ‫إى‬ ٛ‫رؤد‬ ‫خٍْٞ٘ٞخ‬ ‫اد‬‫إ‬‫ّ٘ع‬ ٍِ ‫ّذٍبخٞخ‬TRK‫ر‬‫ز‬‫ْشػ‬
ٛ‫خٕ٘ش‬ ‫ثشنو‬ٗ‫أ‬ ‫مَسشك‬ ‫رؼَو‬ ُ‫أ‬ ِ‫َٝن‬ ٗ‫ٍْشػ‬ٍٜ‫ٗس‬،ٗ‫رؼض‬‫اىخالٝب‬ ‫إّزشبس‬ ‫ص‬ٍ٘ٞ‫اى٘س‬ٗٚ‫ػي‬ ‫اىجقبء‬
‫اىغشغبّٞخ‬ ‫اىخالٝب‬ ‫أَّبغ‬ ٜ‫ف‬ ‫اىسٞبح‬ ‫قٞذ‬.‫رط٘ٝش‬ ٌ‫ر‬Vitrakvi‫م‬‫َثجطبد‬TRK‫اىْشطخ‬ٗ‫ىزثجٞػ‬ ‫اىَصََخ‬
‫اىجشٗرْٞبد‬ ٓ‫ٕز‬.
‫اّذٍبج‬ ٚ‫ػي‬ ‫اىؼث٘س‬ ِ‫َٝن‬TRKِٞ‫ٗاىجبىغ‬ ‫األغفبه‬ ٍِ ‫مو‬ ٚ‫ػي‬ ‫ٗرؤثش‬ ‫اىصيجخ‬ ً‫األٗسا‬ ‫أّ٘اع‬ ٍِ ‫اىؼذٝذ‬ ٜ‫ف‬.
ٓ‫ٕز‬ ‫أعبط‬ ‫مبّذ‬ ٜ‫اىز‬ ‫اىغشٝشٝخ‬ ‫اىزدبسة‬ ٜ‫ف‬‫أظٖشد‬ ، ‫اىَ٘افقخ‬Vitrakvi‫عشٝشٝخ‬ ‫فبئذح‬ٚ‫ػي‬‫اىؼذٝذ‬
‫أّ٘اع‬ ًٍِ‫األٗسا‬‫رىل‬ ٜ‫ف‬ ‫ثَب‬ ،ً‫أٗسا‬، ّْٜٞ‫اىَٞال‬ ً‫اى٘س‬ ، ‫اىذسقٞخ‬ ‫اىغذح‬ ، ‫اىشئخ‬‫اىدٖبص‬ ‫اّغدخ‬ ً‫ٗس‬

3. Vitrakvi (larotrectinib)
Dr. Firas KassabPage3
َٜ‫اىٖع‬ٗ ‫اىيؼبثٞخ‬ ‫اىغذح‬ ، ‫اىشخ٘ح‬ ‫األّغدخ‬ ‫عبسمٍ٘ب‬ ، ُ٘‫اىق٘ى‬ ،‫اىيٞفٞخ‬ ‫اىغبسمٍ٘ب‬ٜ‫اىطفي‬.
Vitrakvi® (larotrectinib)‫دٗائٞخ‬ ‫إخزالغبد‬ ٗ ‫ٍسبرٝش‬ ‫ػذح‬ ‫ْٕبك‬ ٜ‫دٗائ‬ ‫ػالج‬ ٛ‫أ‬ ٜ‫ف‬ ‫مَب‬‫اىغَٞخ‬ ٍِ
‫اىؼصجٞخ‬ٚ‫إى‬ٗ ‫اىنجذٝخ‬ ‫اىغَٞخ‬ِْٞ‫اىد‬ ‫عَٞخ‬.
‫اى‬ ‫األػشاض‬ ‫أمثش‬‫دبّجٞخ‬ٜ‫اىز‬ ‫اىشبئؼخ‬‫ى٘زظذ‬(ٍِٛ‫أ‬‫دسخخ‬‫ى٘زظذ‬)ٜ‫ف‬22٪ٗ‫أ‬‫أمثش‬ٍِٚ‫اىَشظ‬،
‫صٝبدح‬(ALT (45%)،‫صٝبدح‬(AST (45٪،‫ٗفقش‬ً‫اىذ‬(42)٪،‫ٗاىزؼت‬(37)٪،ُ‫ٗاىغثٞب‬(29)٪،
‫ٗاىذٗخخ‬(28)٪،‫ٗاىغؼبه‬(26)٪،‫ٗاىزقٞؤ‬(26)٪،‫ٗاإلٍغبك‬(23)٪،‫ٗاإلعٖبه‬(22)٪‫ٗمبّذ‬
ٟ‫ا‬ ‫غبىجٞخ‬‫اىدبّجٞخ‬ ‫ثبس‬‫اىعبئشح‬‫أصبثذ‬ ‫قذ‬‫أمثش‬ٍِ02ٍِ ‫اىَئخ‬ ٜ‫ف‬ٚ‫ٍشظ‬‫اىذسخخ‬ ٍِ ً‫األٗسا‬ٚ‫األٗى‬ٗ‫أ‬
‫اىثبّٞخ‬.