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Ma ka noiʻi oncology, ke hoʻololi nei nā ana hopena hui, e like me ke ola holomua ʻole (PFS) a me ke ola ʻole maʻi (DFS), ke hoʻololi nei i nā hopena kuʻuna o ke ola holoʻokoʻa (OS) a ua lilo i kumu hoʻāʻo nui no ka ʻae ʻana i ka lāʻau e ka US Food and Drug Administration (FDA) a me ka European Medicines Agency (EMA). Hoʻonui kēia mau hana i ka pono o ka hoʻokolohua lapaʻau a hoʻemi i nā kumukūʻai ma o ka hoʻohui ʻana i nā hanana he nui (e laʻa, ka ulu ʻana o ka tumora, ka maʻi hou, ka make, a me nā mea ʻē aʻe.)

ʻO nā hoʻololi i nā helu hope o nā hoʻokolohua lapaʻau antitumor

I nā makahiki 1970, ua hoʻohana ka FDA i ka helu pane pane (ORR) i ka wā e ʻae ai i nā lāʻau lapaʻau. ʻAʻole a hiki i ka 1980s i ʻike ke Kōmike Kūkākūkā Oncology Drugs (ODAC) a me ka FDA i ka hoʻomaikaʻi ʻana i ke ola, ka maikaʻi o ke ola, ka hana kino, a me nā hōʻailona pili i ka maʻi ʻaʻole i kūlike me ka hoʻoponopono ORR. I nā hoʻokolohua lapaʻau oncology, ʻoi aku ka maikaʻi o ka OS no ke ana ʻana i ka pono lapaʻau pololei. Eia nō naʻe, noho mau ʻo ORR i kahi hopena lapaʻau ʻokoʻa maʻamau i ka wā e noʻonoʻo ai i ka ʻae wikiwiki ʻana i nā lāʻau maʻi maʻi. Ma nā ho'āʻo lima lima hoʻokahi i nā maʻi me nā maʻi maʻi refractory, ua manaʻo ʻia ʻo ORR ma ke ʻano he hopena maʻi mua.

Ma waena o 1990 a me 1999, 30 ka nui o nā ho'āʻo lāʻau lapaʻau maʻi maʻi i ʻae ʻia e FDA i hoʻohana i ka OS ma ke ʻano he kumu mua. E like me ka ulu ʻana o nā lāʻau lapaʻau i hoʻopaʻa ʻia, ua hoʻololi pū ʻia nā wahi hope o ke kino i hoʻohana ʻia e loiloi i nā lāʻau anti-cancer. Ma waena o 2006 a me 2011, ua emi kēlā helu i 14.5 pakeneka. E like me ka emi ʻana o ka nui o nā hoʻokolohua lapaʻau me OS ma ke ʻano he hopena mua, ua maʻalahi ka hoʻohana ʻana i nā ʻāpana hoʻohui e like me PFS a me DFS. Ke alakaʻi nei ke kālā a me nā palena manawa i kēia neʻe ʻana, no ka mea, makemake ʻo OS i nā hoʻokolohua lōʻihi a ʻoi aku ka nui o nā maʻi ma mua o PFS a me DFS. Ma waena o 2010 a me 2020, 42% o nā ho'āʻo hoʻokele randomized (RCTS) i ka oncology i loaʻa iā PFS ko lākou hopena mua. ʻO 67% o nā lāʻau anti-tumor i ʻae ʻia e ka FDA ma waena o 2008 a me 2012 i hoʻokumu ʻia ma nā wahi hope ʻē aʻe, 31% o ia mau mea i hoʻokumu ʻia ma PFS a i ʻole DFS. Ua ʻike ka FDA i nā pono lapaʻau o DFS a me PFS a hiki iā lākou ke hoʻohana ʻia ma ke ʻano he hopena mua i nā hoʻokolohua e ʻimi ana i ka ʻae kānāwai. Ua hoʻolaha pū ka FDA e hiki ke hoʻohana ʻia ka PFS a me nā mea hope ʻē aʻe e hoʻolalelale i ka ʻae ʻia o nā lāʻau lapaʻau no nā maʻi koʻikoʻi a i ʻole ke ola.

E ulu ana nā hopena ʻaʻole wale i ka hoʻomohala ʻia ʻana o nā lāʻau lapaʻau hou, akā e like me ka hoʻomaikaʻi ʻana o nā ʻano hoʻokolohua kiʻi kiʻi a me nā ʻano hana hoʻokolohua. Hōʻike ʻia kēia ma ka hoʻololi ʻana o ka World Health Organization (WHO) me nā pae RECIST no ka Assessment of Efficacy in Solid Tumors (RECIST). Ke aʻo hou aku nā kauka lapaʻau e pili ana i nā maʻi maʻi, ʻike ʻia nā mea maʻi i ka wā paʻa i loaʻa nā micrometastases i ka wā e hiki mai ana. I ka wā e hiki mai ana, ʻaʻole hiki ke hoʻohana hou ʻia kekahi mau hopena, a hiki ke puka mai nā hopena hou e hoʻolalelale i ka ʻae ʻana i ka lāʻau. ʻO ka piʻi ʻana o ka immunotherapy, no ka laʻana, ua alakaʻi i ka hoʻomohala ʻana i nā alakaʻi loiloi hou e like me irRECIST a me iRECIST.

Hōʻuluʻulu manaʻo helu hope

Hoʻohana nui ʻia nā helu hope composite i nā haʻawina lapaʻau, ʻoi aku hoʻi i ka oncology a me ka cardiology. Hoʻonui ka mana helu helu ma ka hoʻonui ʻana i ka nui o nā hanana, e hōʻemi ana i ka nui o ka laʻana, ka manawa hahai, a me ke kālā.
ʻO ka helu hope loa i hoʻohana nui ʻia i ka cardiology ʻo ia nā hanana maʻi cardiovascular nui (MACE). I ka oncology, hoʻohana pinepine ʻia ʻo PFS a me DFS ma ke ʻano he proxies no ke ola holoʻokoʻa (OS). Ua wehewehe ʻia ka PFS e like me ka manawa mai ka randomization a hiki i ka piʻi ʻana o ka maʻi a i ʻole ka make. Hoʻomaopopo pinepine ʻia ka piʻi ʻana o ka tumo paʻa e like me nā kuhikuhi RECIST 1.1, me ka loaʻa ʻana o nā ʻeha hou a me ka hoʻonui ʻia ʻana o nā ʻeha i manaʻo ʻia. ʻO ke ola ʻole hanana hanana (EFS), DFS, a me ka hoʻihoʻi ʻole ʻana (RFS) he mau helu hope hoʻohui maʻamau. Hoʻohana ʻia ʻo EFS i nā hoʻāʻo o ka neoadjuvant therapy, a hoʻohana ʻia ʻo DFS i nā haʻawina hauʻoli o ka adjuvant therapy.

Nā hopena like ʻole i nā lāʻau lapaʻau like ʻole ma nā wahi hopena hui

ʻO ka hōʻike ʻana i nā hopena hui pū kekahi hiki ke alakaʻi i ka manaʻo e pili ana ka hopena lapaʻau i kēlā me kēia hanana ʻāpana, ʻaʻole ia he ʻoiaʻiʻo. ʻO kahi manaʻo koʻikoʻi i ka hoʻohana ʻana i nā mea hoʻopau composite ʻo ia ka hoʻololi ʻana i nā ʻāpana i ke ʻano like. Eia nō naʻe, ʻo nā hopena o ka antitumor therapy ma nā ʻano like ʻole e like me ka ulu ʻana o ka tumo mua, ka metastasis, a me ka make i kekahi manawa e hele i kahi ʻaoʻao. No ka laʻana, hiki i ka lāʻau ʻawaʻawa ke hōʻemi i ka laha ʻana o ka maʻi maʻi akā hoʻonui i ka make. ʻO kēia ka hihia i ka BELLINI hoʻokolokolo o nā maʻi me ka relapsed / refractory multiple myeloma, kahi i hoʻomaikaʻi ai ka PFS akā haʻahaʻa ka OS ma muli o ke kiʻekiʻe o ka maʻi e pili ana i ka mālama ʻana.

Eia kekahi, aia nā ʻikepili preclinical e hōʻike ana i ka hoʻohana ʻana i ka chemotherapy e hōʻemi i ka maʻi maʻi mua e hoʻolalelale i ka laha mamao i kekahi mau hihia no ka mea koho ka chemotherapy i nā pūnaewele kumu e hoʻomaka ai ka metastasis. ʻAʻole hiki ke hoʻopaʻa ʻia ke kuhiakau kuhikuhi i ka wā he nui nā hanana i ka hopena composite, e like me ke ʻano o kekahi mau wehewehe o PFS, EFS, a me DFS. No ka laʻana, hoʻohana pinepine nā hoʻāʻo ʻana o ka allogeneic hematopoietic stem cell transplantation therapy i kahi endpoint composite e pili ana i ka make, ka hoʻi hou ʻana o ka maʻi kanesa, a me ka maʻi graft-versus-host (GVHD), i kapa ʻia ʻo GVHD free RFS (GRFS). ʻO nā lāʻau lapaʻau e hōʻemi ana i ka ulu ʻana o GVHD hiki ke hoʻonui i ka nui o ka hoʻi hou ʻana o ka maʻi kanesa, a me ka hope. I kēia hihia, pono e nānā kaʻawale ʻia ka GVHD a me ka hoʻihoʻi ʻana i nā helu no ke ana pono ʻana i ka ratio o ka pono-pōmaikaʻi o ka lapaʻau.

ʻO ka hōʻike maʻamau o nā helu hanana like ʻole no nā hopena paʻakikī e hōʻoia i ka hopena o ka mālama ʻana i kēlā me kēia ʻāpana i ke ala like; ʻO kēlā me kēia "ʻano heterogeneity qualitative" (ʻo ia hoʻi, nā ʻokoʻa o ke kuhikuhi) alakaʻi i ka hoʻohana pono ʻole ʻana i nā helu hope.

Manaʻo ka EMA i "ka nānā ʻana o kēlā me kēia ʻano hanana me ka hoʻohana ʻana i nā papa hōʻuluʻulu wehewehe a, inā kūpono, ka loiloi hoʻokūkū hoʻokūkū e ʻimi i ka hopena o ka mālama ʻana i kēlā me kēia hanana". Eia nō naʻe, ma muli o ka lawa ʻole o ka mana helu o nā haʻawina he nui, ʻaʻole hiki ke ʻike ʻia nā ʻokoʻa koʻikoʻi o nā hanana ʻāpana i nā hopena composite.

ʻAʻole maopopo i ka hōʻike ʻana i nā hanana endpoint composite

Ma nā ho'āʻo cardiology, he hana maʻamau ka hāʻawi ʻana i ka hanana o kēlā me kēia hanana ʻāpana (e like me ka hahau ʻana, myocardial infarction, halemai, a me ka make) me ka MACE composite endpoint. Eia nō naʻe, no ka PFS a me nā helu hope ʻē aʻe i nā hoʻokolohua lapaʻau oncology, ʻaʻole pili kēia criterion. ʻO kahi loiloi o 10 mau noiʻi hou i paʻi ʻia i loko o ʻelima mau puke moʻolelo oncology kiʻekiʻe i hoʻohana i ka PFS ma ke ʻano he hopena i ʻike ʻia he ʻekolu wale nō (6%) i hōʻike i nā make a me nā hanana o ka piʻi ʻana o ka maʻi; Hoʻokahi wale nō haʻawina i ʻokoʻa ma waena o ka holomua kūloko a me ka metastasis mamao. Eia kekahi, hoʻokahi haʻawina i ʻokoʻa ma waena o ka holomua kūloko a me kahi mamao, akā ʻaʻole i hāʻawi i ka helu o ka make ma mua o ka piʻi ʻana o ka maʻi.

ʻAʻole maopopo nā kumu o ka ʻokoʻa o ka hōʻike ʻana i nā kūlana no nā helu hope i ka cardiology a me ka oncology. ʻO kekahi mea hiki ke hoʻohālikelike ʻia nā helu hope e like me PFS a me DFS he mau hōʻailona efficacy. Ua hoʻomaka ʻia ʻo MACE mai nā hopena palekana a ua hoʻohana mua ʻia i ke aʻo ʻana i nā pilikia o ka hana coronary percutaneous. Loaʻa i nā keʻena hoʻoponopono nā kūlana kiʻekiʻe no ka hōʻike ʻana i nā hopena palekana, no laila pono ka palapala kikoʻī o nā hanana ʻino i nā hoʻokolohua lapaʻau. I ka wā i hoʻohana nui ʻia ai ka MACE ma ke ʻano he hopena o ka pono, ua lilo paha ia i mea maʻamau ka hāʻawi ʻana i nā nui o kēlā me kēia hanana. ʻO ke kumu ʻē aʻe o nā kūlana hōʻike like ʻole, ʻo ia ka PFS i manaʻo ʻia he hōʻuluʻulu o nā hanana like, ʻoiai ʻo MACE ka mea i manaʻo ʻia he hōʻuluʻulu o nā hanana like ʻole (e laʻa, stroke vs. myocardial infarction). Eia nō naʻe, ʻokoʻa ka ulu ʻana o ka maʻi maʻi mua a me nā metastases mamao, ʻoi aku ka nui o ka hopena maʻi. ʻO kēia mau wehewehe ʻana he mea noʻonoʻo, akā maopopo ʻaʻole kekahi o lākou e hōʻoia i kahi hōʻike piha ʻole. No nā hoʻāʻo oncology e hoʻohana ana i nā helu hope, ʻoi aku ka nui o ka hopena o ka composite ka hopena mua a i ʻole ke hoʻohana ʻia no nā kumu hoʻoponopono, a i ka wā e loaʻa ai ka hopena composite ma ke ʻano he hope lua, pono e lilo ka hōʻike ʻana i nā hanana hanana i mea maʻamau.