Immunotherapy da maganin ciwon daji
A cikin 'yan shekarun nan, shahararriyar immunotherapy a fagen ilimin oncology na ci gaba da karuwa. Lancet Oncol ya buga sakamakon farko na binciken Keynote-012 yana kimanta tasirin PD-L1 inhibitor pembrolizumab a cikin marasa lafiya da ciwon daji na ciki a ranar 3 ga Mayu, wanda ya ja hankalin mutane da yawa. Farfesa Elizabeth C Smyth na Asibitin Royal Marsden da ke Ingila ta fassara binciken, wanda zai iya kawo mana wasu tunani da zaburarwa.
Hasashen ciwon daji na ciki na ci gaba ba shi da kyau, kuma ƙasa da kashi 10-15% na marasa lafiya na ƙwayar cuta na iya rayuwa sama da shekaru 2. Trastuzumab da ramoluzumab don kula da layi na biyu na masu cutar kansa na ciki na HER2 tabbatacce na iya inganta rayuwa gaba ɗaya. Saboda akwai misalai da yawa na gazawar magungunan warkarwa a fagen ciwon daji na ciki, da alama waɗannan magungunan ba su sami nasara kaɗan ba. A cikin wannan ƙalubalen halin yanzu na ci gaban ciwon daji na ciki, binciken Keynote-012 wanda Farfesa Kei Muro ya gudanar tare da abokan aiki da farko ya nuna sakamako mai kyau, yana nuna cewa masu hana PD-L1 suna da ƙima mai ƙima a cikin ciwon daji na ciki.
Sakamakon binciken Keynote-012 abin mamaki ne
A cikin binciken Keynote-012, PD-L1-tabbatattun marasa lafiya waɗanda ke da ciwon daji na ciki sun sami anti-PD-1 antibody pembrolizumab har zuwa ci gaban cutar ko abubuwan da ba za a iya jurewa ba. Binciken ya duba jimlar marasa lafiya 162 da ke fama da ciwon daji na ciki na ciki, wanda 65 (40%) sun kasance tabbatattu ga furucin PD-L1, kuma a ƙarshe an shigar da marasa lafiya 39 (24%) a cikin wannan binciken na Phase 1B mai yawa. Abin farin ciki, 17 daga cikin marasa lafiya 32 (53%) sun sami koma baya na tumor; 8 na 36 (22%) marasa lafiya tare da ƙimar inganci sun tabbatar da gafartawa. Wannan ƙimar gafarar ta yi daidai da sakamakon gwajin rigakafin rigakafi a cikin wasu cututtukan daji, tare da lokacin amsa matsakaici na makonni 40, da 4 na marasa lafiya 36 (11%) tare da gafarar cututtuka ba su nuna ci gaban cutar ba kamar lokacin rahoton. Kamar yadda aka zata, marasa lafiya 9 (23%) sun sami abubuwan da suka shafi rigakafi. Babu marasa lafiya da suka daina magani saboda abubuwan da ke da alaƙa da rigakafi. Idan aka kwatanta da 11% zuwa 30% na marasa lafiya a cikin gwajin chemotherapy na layi na biyu, sakamakon ya kasance abin mamaki. Dangane da gaskiyar cewa sakamakon rayuwa na sabbin gwaje-gwajen asibiti na ciwon daji na duniya na baya-bayan nan ya shafi bambance-bambancen yanki, Kei Muro da abokan aiki sun ƙara tabbatar da cewa rayuwar marasa lafiyar Asiya da marasa Asiya a gwajin Keynote-012 iri ɗaya ne.
Shin bayanin PD-L1 zai iya yin hasashen ingancin rigakafin rigakafi?
Babban gwajin-012 gwajin gwajin yana amfani da immunohistochemistry don gano bayyanar PD-L1. Marasa lafiya waɗanda ke da ƙwayoyin tumor, ƙwayoyin rigakafi ko waɗannan rukunin sel guda biyu suna buƙatar bayyana aƙalla 1% na PD-L1 don su cancanci gwajin. Daga nan marubucin ya sake tantance matsayin PD-L1 ta amfani da gwaje-gwaje daban-daban. Sakamakon gwajin na biyu yana nuna cewa bayyanar PD-L1 a cikin ƙwayoyin rigakafi, ba ƙwayoyin tumor ba, suna da alaƙa da ingancin pembrolizumab a cikin ciwon daji na ciki. Abu na biyu, 8 na samfuran biopsy 35 waɗanda za a iya kimantawa suna da mummunan sakamako PD-L1. Waɗannan sakamakon suna nuna rikitarwa na binciken PD-L1 gabaɗaya, musamman kimantawa masu binciken halittu don ciwon daji na ciki. Wannan karkacewar na iya kasancewa saboda canje-canje masu ƙarfi a cikin bayanin PD-L1 bayan jiyya, bambance-bambancen hanyoyin kimantawa, da bambancin ciwon daji na ciki. Don haka, ba a sani ba ko a cikin gwaje-gwajen asibiti na baya ba tare da gwajin biomarker ba, wasu marasa lafiya da alamun marasa lafiya PD-L1 marasa lafiya waɗanda suka karɓi maganin rigakafin PD1 don yaƙar cutar suna da alaƙa da bambancin magana na mai biomarker, Ko kuma akwai ainihin daidaituwa tsakanin masu nuna halitta da inganci. Ana buƙatar ƙarin bincike
Hanya mafi kyau don kimanta faɗar PD-L1 kuma ko gaskiya ce kuma mai tasiri mai ba da gudummawa a cikin rigakafin cutar kansa na ciki. Marubutan sun kuma ba da rahoton sakamakon farko na interferon gamma gene expression a matsayin mai nazarin halittu don tsinkayar raunin nama na farko. Idan an tabbatar da wannan sakamakon, zai iya taimakawa don guje wa wasu matsalolin da suka shafi immunohistochemistry a nan gaba.
Abubuwan da ke buƙatar ƙarin tunani
Tabbas, ƙaramin gwajin samfurin kamar Maɓallin-012 babu makawa yana da wasu matsaloli. Na farko, ba a sani ba ko akwai mu'amala tsakanin chemotherapy da aka karɓa a baya da ingancin pembrolizumab. Kodayake wasu marasa lafiya da ke amsawa sun karɓi layi na farko ko ƙasa da chemotherapy kafin pembrolizumab, yawancin (63%) masu amsawa marasa lafiya sun karɓi layi na biyu ko fiye da maganin cutar tumor. Bugu da ƙari, Maɓalli-012 ƙaramin samfuri ne na gwajin asibiti na farko kuma ba za a iya haɗa shi da yawancin marasa lafiya da ke fama da ciwon daji na ciki tare da gajeriyar rayuwa ba, wanda na iya haifar da ƙarancin amsawar jinkiri da ƙarya lokaci-lokaci.
Sakamakon ci gaba ba shi da gamsarwa. Gwaje -gwajen asibiti da yawa da ke gudana suna ƙoƙarin tantance mafi kyawun lokacin rigakafin immunotherapy ga masu cutar kansa na ciki. Na biyu, kodayake a cikin ka'idar, marasa lafiya da ke fama da ciwon daji na ciki tare da microsomes marasa ƙarfi yakamata su fi dacewa da rigakafin rigakafi, kuma
A cikin gwajin Keynote-012, rabin marasa lafiya ne kawai waɗanda ke da rashin lafiyar microsatellite da aka yi amfani da su tare da pembrolizumab suka amsa. Wannan nau'in nau'in ciwon daji na ciki yana lissafin kashi 22% na jimlar masu ciwon daji na ciki kuma ya cancanci ƙarin karatu. A ƙarshe, sigogi waɗanda ke kimanta sakamako mai kyau na wannan gwajin asibiti na rigakafin cutar kansa na ciki shima yana buƙatar yin la'akari sosai. Yawan marasa lafiya da suka sami gafarar cututtuka a gwajin Keynote-012 ya yi ƙasa da na gwajin RAINBOW tare da paclitaxel da haɗuwar ramolizumab. A zahiri, gwajin Maɓallin-012 ba shi da kyau daga ma'anar ƙididdiga zalla. Marasa lafiya waɗanda suka amsa magani ba su nuna ingantaccen ci gaba ba a cikin ci gaban da babu ci gaba da rayuwa gaba ɗaya. A nan gaba, gwaje -gwajen asibiti masu gudana kuma suna buƙatar kula da waɗannan batutuwan.
Gwaje-gwajen asibiti da suka shafi anti-CTLA-4 da anti-PD-1 jiyya sun yi nasara sosai a cikin melanoma. Idan aka kwatanta, sakamakon gwajin Maɓallin-012 da alama yana da ɗan kaffa-kaffa. Koyaya, yawan mace -macen ciwon daji na ciki a duk duniya ya ninka na melanoma sau uku, don haka sakamakon wannan binciken har yanzu yana da mahimmanci. Ga mafi yawan masu fama da cutar sankara na ciki waɗanda basu da ingantattun magunguna, binciken da ake samu yanzu shine mataki na farko mai kayatarwa don cimma nasarar yaɗuwar cutar a cikin 'yan shekarun nan. Sakamakon farko na binciken Keynote-012 yana kimanta ingancin PD-L1 inhibitor pembrolizumab a cikin marasa lafiya da ciwon daji na ciki a ranar 3 ga Mayu, wanda ya ja hankali sosai. Farfesa Elizabeth C Smyth na asibitin Royal Marsden a Ingila ya fassara binciken, wanda zai iya kawo mana wasu tunani da wahayi.
Hasashen ciwon daji na ciki na ci gaba ba shi da kyau, kuma ƙasa da kashi 10-15% na marasa lafiya na ƙwayar cuta na iya rayuwa sama da shekaru 2. Trastuzumab da ramoluzumab don kula da layi na biyu na masu cutar kansa na ciki na HER2 tabbatacce na iya inganta rayuwa gaba ɗaya. Saboda akwai misalai da yawa na gazawar magungunan warkarwa a fagen ciwon daji na ciki, da alama waɗannan magungunan ba su sami nasara kaɗan ba. A cikin wannan ƙalubalen halin yanzu na ci gaban ciwon daji na ciki, binciken Keynote-012 wanda Farfesa Kei Muro ya gudanar tare da abokan aiki da farko ya nuna sakamako mai kyau, yana nuna cewa masu hana PD-L1 suna da ƙima mai ƙima a cikin ciwon daji na ciki.
Sakamakon binciken Keynote-012 abin mamaki ne
A cikin binciken Keynote-012, PD-L1-tabbatattun marasa lafiya waɗanda ke da ciwon daji na ciki sun sami anti-PD-1 antibody pembrolizumab har zuwa ci gaban cutar ko abubuwan da ba za a iya jurewa ba. Binciken ya duba jimlar marasa lafiya 162 da ke fama da ciwon daji na ciki na ciki, wanda 65 (40%) sun kasance tabbatattu ga furucin PD-L1, kuma a ƙarshe an shigar da marasa lafiya 39 (24%) a cikin wannan binciken na Phase 1B mai yawa. Abin farin ciki, 17 daga cikin marasa lafiya 32 (53%) sun sami koma baya na tumor; 8 na 36 (22%) marasa lafiya tare da ƙimar inganci sun tabbatar da gafartawa. Wannan ƙimar gafarar ta yi daidai da sakamakon gwajin rigakafin rigakafi a cikin wasu cututtukan daji, tare da lokacin amsa matsakaici na makonni 40, da 4 na marasa lafiya 36 (11%) tare da gafarar cututtuka ba su nuna ci gaban cutar ba kamar lokacin rahoton. Kamar yadda aka zata, marasa lafiya 9 (23%) sun sami abubuwan da suka shafi rigakafi. Babu marasa lafiya da suka daina magani saboda abubuwan da ke da alaƙa da rigakafi. Idan aka kwatanta da 11% zuwa 30% na marasa lafiya a cikin gwajin chemotherapy na layi na biyu, sakamakon ya kasance abin mamaki. Dangane da gaskiyar cewa sakamakon rayuwa na sabbin gwaje-gwajen asibiti na ciwon daji na duniya na baya-bayan nan ya shafi bambance-bambancen yanki, Kei Muro da abokan aiki sun ƙara tabbatar da cewa rayuwar marasa lafiyar Asiya da marasa Asiya a gwajin Keynote-012 iri ɗaya ne.
Shin bayanin PD-L1 zai iya yin hasashen ingancin rigakafin rigakafi?
Babban gwajin-012 gwajin gwajin yana amfani da immunohistochemistry don gano bayyanar PD-L1. Marasa lafiya waɗanda ke da ƙwayoyin tumor, ƙwayoyin rigakafi ko waɗannan rukunin sel guda biyu suna buƙatar bayyana aƙalla 1% na PD-L1 don su cancanci gwajin. Daga nan marubucin ya sake tantance matsayin PD-L1 ta amfani da gwaje-gwaje daban-daban. Sakamakon gwajin na biyu yana nuna cewa bayyanar PD-L1 a cikin ƙwayoyin rigakafi, ba ƙwayoyin tumor ba, suna da alaƙa da ingancin pembrolizumab a cikin ciwon daji na ciki. Abu na biyu, 8 na samfuran biopsy 35 waɗanda za a iya kimantawa suna da mummunan sakamako PD-L1. Waɗannan sakamakon suna nuna rikitarwa na binciken PD-L1 gabaɗaya, musamman kimantawa masu binciken halittu don ciwon daji na ciki. Wannan karkacewar na iya kasancewa saboda canje-canje masu ƙarfi a cikin bayanin PD-L1 bayan jiyya, bambance-bambancen hanyoyin kimantawa, da bambancin ciwon daji na ciki. Don haka, ba a sani ba ko a cikin gwaje-gwajen asibiti na baya ba tare da gwajin biomarker ba, wasu marasa lafiya da alamun marasa lafiya PD-L1 marasa lafiya waɗanda suka karɓi maganin rigakafin PD1 don yaƙar cutar suna da alaƙa da bambancin magana na mai biomarker, Ko kuma akwai ainihin daidaituwa tsakanin masu nuna halitta da inganci. Ana buƙatar ƙarin bincike
Hanya mafi kyau don kimanta faɗar PD-L1 kuma ko gaskiya ce kuma mai tasiri mai ba da gudummawa a cikin rigakafin cutar kansa na ciki. Marubutan sun kuma ba da rahoton sakamakon farko na interferon gamma gene expression a matsayin mai nazarin halittu don tsinkayar raunin nama na farko. Idan an tabbatar da wannan sakamakon, zai iya taimakawa don guje wa wasu matsalolin da suka shafi immunohistochemistry a nan gaba.
Abubuwan da ke buƙatar ƙarin tunani
Tabbas, ƙaramin gwajin samfurin kamar Maɓallin-012 babu makawa yana da wasu matsaloli. Na farko, ba a sani ba ko akwai mu'amala tsakanin chemotherapy da aka karɓa a baya da ingancin pembrolizumab. Kodayake wasu marasa lafiya da ke amsawa sun karɓi layi na farko ko ƙasa da chemotherapy kafin pembrolizumab, yawancin (63%) masu amsawa marasa lafiya sun karɓi layi na biyu ko fiye da maganin cutar tumor. Bugu da ƙari, Maɓalli-012 ƙaramin samfuri ne na gwajin asibiti na farko kuma ba za a iya haɗa shi da yawancin marasa lafiya da ke fama da ciwon daji na ciki tare da gajeriyar rayuwa ba, wanda na iya haifar da ƙarancin amsawar jinkiri da ƙarya lokaci-lokaci.
Sakamakon ci gaba ba shi da gamsarwa. Gwaje -gwajen asibiti da yawa da ke gudana suna ƙoƙarin tantance mafi kyawun lokacin rigakafin immunotherapy ga masu cutar kansa na ciki. Na biyu, kodayake a cikin ka'idar, marasa lafiya da ke fama da ciwon daji na ciki tare da microsomes marasa ƙarfi yakamata su fi dacewa da rigakafin rigakafi, kuma
A cikin gwajin Keynote-012, rabin marasa lafiya ne kawai waɗanda ke da rashin lafiyar microsatellite da aka yi amfani da su tare da pembrolizumab suka amsa. Wannan nau'in nau'in ciwon daji na ciki yana lissafin kashi 22% na jimlar masu ciwon daji na ciki kuma ya cancanci ƙarin karatu. A ƙarshe, sigogi waɗanda ke kimanta sakamako mai kyau na wannan gwajin asibiti na rigakafin cutar kansa na ciki shima yana buƙatar yin la'akari sosai. Yawan marasa lafiya da suka sami gafarar cututtuka a gwajin Keynote-012 ya yi ƙasa da na gwajin RAINBOW tare da paclitaxel da haɗuwar ramolizumab. A zahiri, gwajin Maɓallin-012 ba shi da kyau daga ma'anar ƙididdiga zalla. Marasa lafiya waɗanda suka amsa magani ba su nuna ingantaccen ci gaba ba a cikin ci gaban da babu ci gaba da rayuwa gaba ɗaya. A nan gaba, gwaje -gwajen asibiti masu gudana kuma suna buƙatar kula da waɗannan batutuwan.
Gwaje-gwajen asibiti da suka shafi anti-CTLA-4 da anti-PD-1 jiyya sun yi nasara sosai a cikin melanoma. Idan aka kwatanta, sakamakon gwajin Maɓallin-012 da alama yana da ɗan kaffa-kaffa. Koyaya, yawan mace -macen ciwon daji na ciki a duk duniya ya ninka na melanoma sau uku, don haka sakamakon wannan binciken har yanzu yana da mahimmanci. Ga mafi yawan marasa lafiya na ciwon daji na ciki waɗanda ba su da ingantattun jiyya, abubuwan da aka gano a yanzu shine mataki na farko mai kayatarwa don cimma gafarar cutar na dogon lokaci.
