I-Pulmonary kunye ne-thyroid carcinoma: I-FDA ivuma unyango kunye neRetevmo
Ulawulo lokuTya iziyobisi (i-FDA) lwamkele i-Retevmo (selpercatinib) yeentlobo ezintathu zonyango lomhlaza ezithi ziguqule (zitshintsha) kuhlobo lwe-RET (Luhlengahlengisiwe ngexesha lokuTshintsha).
I-FDA, yamkela i-Retevmo kunyango “oluncinci lweeseli” unyango lwe-pulmonary carcinoma
Ngokukodwa, iRetevmo iye yamkelwa kunyango lweentlobo ezahlukeneyo zomhlaza. Inokuhanjiswa:
- yenza umhlaza wemiphunga engengawo omncinci kwiseli (NSCLC) kwizigulana zabantu abadala
- Umhlaza ophambili we-medullary ye-medullary (TCM) okanye we-TCM osasazekileyo, kwizigulana ezineminyaka eli-12 ubudala okanye ngaphezulu
- RET fusion-positive advanced cancer umdlavuza we-thyroid kwizifundo ezineminyaka eli-12 ubudala okanye ngaphezulu
I-retemvo lonyango lokuqala oluchaziweyo lomhlaza ngokutshintshwa kohlobo lwe-RET. Ukuvunywa kukaRetevmo, i-FDA yaxhomekeka kwiziphumo zovavanyo lweklinikhi olwabandakanya izigulana uhlobo ngalunye lomhlaza.
Ngexesha lokuvavanywa kweklinikhi, abaguli bafumana i-Retevmo i-160 mg ngomlomo kabini ngosuku-de kube kuqhubekeka ngezifo okanye-kungavakali ityhefu. Umgangatho wokuphendula ngokubanzi (i-ORR), obonisa ipesenti yezigulana ezazinomthamo othile wokukhubazeka kwesisu, kunye nexesha lokuphendula (i-DOR) zithathwe njengawona manyathelo esiphumo sokusebenza ngempumelelo.
Ukusebenza kakuhle kunyango lwe-NSCLC kuvavanyiwe kwizigulana zabantu abadala eziyi-105 ezine-RET-fusion Fusion NSCLC, ngaphambili eyanyangwa ngeplatinamotherapy. I-ORR kwizigulana ezingama-105 ibingama-64%.
Kwiipesenti ezingama-81 zezigulana ezaziphendula unyango, ixesha lokuphila lalililitye elincinci kangangeenyanga ezintandathu.
I-FDA kunye nokusebenza kweRetevmo
Ukusebenza kakuhle kweRetemvo kwavavanywa kwizigulana ezingama-39 ezine-FET-positive fusion NSCLC engazange yanyangwa ngaphambili. Ezi zigulana, i-ORR yayiyi-84%. Kwiipesenti ezingama-58 zeempendulo zonyango, ixesha elingaphantsi kweenyanga ezintandathu ubuncinci.
Ukusebenza kakuhle kunyango lwe-MTC kubantu abadala nakwizigulana zabantwana kwavavanywa kwizigulana ezili-143 ezine-RET-mutant TCM yangaphambili, eyanyangwa nge-cabozantinib, vandetanib okanye bobabini, nakwizigulana ezine-RET-mutant TCM yangaphambili eyayingazange Ufumene unyango nge-cabozantinib okanye vandetanib.
I-ORR kwizigulana ezingama-55 ezazanyangwa ngaphambili yayingama-69%. Kwiipesenti ezingama-76 zezigulana ezaziphendula kunyango, ixesha lazo lalingangeenyanga ezintandathu.
Ukusebenza kakuhle kwavavanywa kwizigulana ezingama-88 ezazinganyangeki. I-ORR yezi zigulana yayingama-73%. Kwiimeko ezingama-61% zokuphendula kunyango, ixesha elinokuba lienyanga ezintandathu ubuncinci.
Ukusebenza kweziyobisi kuLawulo lokutya kunye noLawulo lweeDrug (FDA)
Ukusebenza kweRetevmo kunyango lomhlaza wesibeleko we-Fusion-positive RET kubantu abadala nakwizigulana zabantwana abaneminyaka eli-12 nangaphezulu kwavavanywa kwisifundo esathi sabhalisa izigulana ezili-19 ezinomhlaza we-RET we-RET owayenomdla kwi-iodine ye-radioactive (RAI), ukuba ukhetho olufanelekileyo lonyango, kwaye ngaphambili belufumene olunye unyango lwenkqubo, kunye nezigulana ezisi-8 ezine-RET ye-carcinoma ye-fusion-Reflexion, i-RAI kodwa ebengalufumenanga naluphi na unyango olongezelelweyo.
I-ORR, kwizigulana ezili-19 ezazinyangwa ngaphambili, yayiyi-79%. Kwiipesenti ezingama-87 zeempendulo zokunyangwa, ixesha elingaphantsi kweenyanga ezintandathu. Kwizigulana ezisi-8 ezazingafumananga naluphi na unyango ngaphandle kwe-RAI, i-ORR yayili-100%.
Kwi-75% yezigulana, impendulo ihlale okungenani iinyanga ezintandathu. Iziphumo ezixhaphakileyo ze-Retevmo yayikukunyuka kwe-enzymes aspartate aminotransferase (AST) kunye ne-alanine aminotransferase (ALT) esibindini, ukunyusa iswekile yegazi, ukunciphisa ukubalwa kweeseli zegazi elimhlophe, ukuncipha kwe-albhamuin egazini, ukuncipha kwe-calcium egazini, umlomo owomileyo, isifo sohudo, i-creatinine eyandayo, ukunyuka kwe-alkaline phosphatase, uxinzelelo lwegazi, ukudinwa, ukudumba emzimbeni okanye imilenze, ukubala kweplatelethi ephantsi, ukunyuka kwe-cholesterol, iqashiso, ukuqunjelwa kunye nokunciphisa isodium egazini.
Phakathi kweziphumo ebezingalindelekanga ezinokubangelwa yiRetevmo, hepatotoxicity, uxinzelelo lwegazi oluphezulu, ukwandiswa kwexesha lokuphumla kwe-QT, ukopha kunye neziphumo zomzimba zonke.
URetevmo ufumene inkedama yeziyobisi, Uqwalaselo oluphambili kunye nonyango oluphumelelayo kwi-FDA kwaye yamkelwe ngenkqubo yokuvunywa okukhawulezayo.