Immunotherapy uye kenza kurapwa
In recent years, the popularity of immunotherapy in the field of oncology is continuing to rise. Lancet Oncol published the preliminary results of the Keynote-012 study evaluating the efficacy of the PD-L1 inhibitor pembrolizumab in patients with advanced gastric cancer on May 3, which attracted a lot of attention. Professor Elizabeth C Smyth of the Royal Marsden Hospital in England interpreted the study, which can bring us some thoughts and inspirations.
Kufungidzira kwekenza yemudumbu yepamusoro kwakashomeka, uye isingasviki 10-15% yevarwere ve metastatic vanogona kurarama kweanopfuura makore maviri. Trastuzumab uye ramoluzumab yechipiri-mutsara kurapwa kweHER2-inovhenekera gastric kenza varwere vanogona zvishoma kuvandudza kupona kwese. Nekuti pane mienzaniso mizhinji yekundikana kwemishonga yekurapa mumunda wekenza yemudumbu, zvinoita sekunge mishonga iyi yakawana budiriro shoma. Mune ino yakaoma mamiriro eazvino epamberi gomarara yekurapa kurapwa, iyo Keynote-2 yekudzidza yakaitwa naPurofesa Kei Muro uye vaaishanda navo pakutanga vakaratidza mhedzisiro, zvichiratidza kuti PD-L012 inhibitors ine mukana wekurapa kukosha mune yakakwira gastric cancer.
Zvabuda zveKeynote-012 kudzidza zvinoshamisa
Muchidzidzo cheKeynote-012, varwere vePD-L1-vane chirwere chegomarara repamberi vakagamuchira anti-PD-1 antibody pembrolizumab kusvika pakukura kwechirwere kana zviitiko zvisinga tsindike. Chidzidzo ichi chakaongorora huwandu hwevarwere zana nemakumi mapfumbamwe nemaviri vane gomarara repamberi remudumbu, iro 162 (65%) yaive netarisiro yePD-L40, uye pakupedzisira 1 (39%) varwere vakanyoreswa mune ino yepasi rose multicenter Phase 24B kudzidza. Zvinofadza, 1 yevarwere makumi matatu nevaviri (17%) vakasangana neremarara regression; 32 ye53 (8%) varwere vane hunovhenekerwa hunoshanda vakasimbisa kuregererwa zvishoma. Iyi yekuregererwa mwero inoenderana nemhedzisiro yemununotherapy miedzo mune mamwe kanzira, ine nguva yepakati yekupindura kwemasvondo makumi mana, uye 36 yevarwere makumi matatu nevatatu (22%) vane kuregererwa kwechirwere havana kuratidza kukura kwechirwere senge yenguva yekubika. Sezvinotarisirwa, 40 varwere (4%) vakasangana nezviitiko zvakasangana zvine chekuita nemuviri. Hapana varwere vakasiya kurapwa nekuda kwezviitiko zvakashata zvine chekuita ne immune. Zvichienzaniswa ne36% kusvika 11% yevarwere mune yechipiri-mutsara chemotherapy kutongwa, mhedzisiro yacho yakashamisa kwazvo. Tichifunga nezve chokwadi chekuti mhedzisiro yekupona yazvino gomarara repasi rose gastric kiriniki miedzo inokanganiswa nemisiyano yedunhu, Kei Muro nevamwe vaaishanda navo zvakaratidza zvakare kuti kupona kwevarwere veAsia nevasiri veAsia mukutongwa kweKeynote-9 kwakafanana.
Ko kutaura kwePD-L1 kunogona kufanotaura kushanda kwemununotherapy?
Keynote-012 bvunzo yekuongorora inoshandisa immunohistochemistry kuti ione kutaura kwePD-L1. Varwere vane tumarara maseru, maseru ekudzivirira kana aya maviri maseru maseru vanofanirwa kuratidza angangoita 1% yePD-L1 kuti vakwanise kutongwa. Munyori akabva aongororazve chimiro chePD-L1 achishandisa assays dzakasiyana. Mhedzisiro yechipiri assay inoratidza kuti kutaura kwePD-L1 mumasero ekudzivirira muviri, kwete maseru emota, kunoenderana nekushanda kwepembrolizumab mukenza yemudumbu. Kechipiri, masere makumi matatu nemakumi matatu nemashanu ebhaopsy mienzaniso inogona kuongororwa yaive neyakaipa PD-L8 mhedzisiro. Mhedzisiro iyi inoratidza kuomarara kwePD-L35 kuongorora zvakanyanya, kunyanya kuongororwa kwema biomarkers ekenza yemudumbu. Uku kutsauka kunogona kunge kuri nekuda kweshanduko ine simba muPD-L1 kutaura mushure mekurapwa, mutsauko munzira dzekuongorora, uye heterogeneity yegomarara repamuviri. Naizvozvo, hazvizivikanwe kana mumakiriniki epfuura akaedzwa pasina biomarker kuongorora, vamwe varwere vane zvinoita kunge PD-L1 yakaipa varwere vakagashira anti-PD1 mishonga yekurapa kwekuregererwa kwechirwere vaive nehukama nehunhu hwekutaura kwebiomarker, Kana kana paine kuwirirana chaiko. pakati biomarkers uye kushanda. Kuwedzera kutsvagurudza kunodiwa
Nzira yakanakisa yekutarisa PD-L1 kutaura uye kuti ichokwadi here uye inoshanda yekufungidzira biomarker mune gastric cancer cancer. Vanyori vanotaurawo mhedzisiro yekutanga yeiyo interferon gamma gene expression seye biomarker yepuru tishu lesion yakazvimirira kufanotaura. Kana uyu mhedzisiro yakaverengerwa, zvinogona kubatsira kudzivirira mamwe matambudziko ane chekuita neyemunohistochemistry mune ramangwana.
Nyaya dzinoda kumberi kufunga
Ehe, bvunzo diki yemuenzaniso senge Keynote-012 zvinonzwisisika ine mamwe matambudziko. Kutanga, hazvizivikanwe kana paine kudyidzana pakati pemakemikari akagashirwa kare uye kushanda kwepembrolizumab. Kunyangwe vamwe vanopindura varwere vanga vangogamuchira yekutanga-mutsara kana mashoma chemotherapy pamberi pembrolizumab, vazhinji (63%) vanopindura varwere vanga vagamuchira wechipiri-mutsara kana kupfuura anti-bundu kurapwa. Zvakare, Keynote-012 idiki sampuro yekutanga kiriniki miedzo uye haigone kuverengerwa muvazhinji varwere vane gomarara repamberi remudumbu nekupona pfupi, izvo zvinogona kuita immunotherapy-zvine hukama neinononoka kupindura mitengo uye dzimwe nguva manyepo.
Mhedzisiro yekufambira mberi haina kugutsikana. Akawanda anoenderera mberi emakiriniki miedzo ari kuyedza kuona yakanakisa immunotherapy nguva hwindo yevarwere vegomarara remudumbu. Chechipiri, kunyangwe mune fungidziro, varwere vane gomarara remudumbu vane microsomes isina kugadzikana vanofanirwa kuve vanokodzera immunotherapy, uye
MuKeynote-012 kuyedza, chete hafu yevarwere vane microsatellite kusagadzikana kwakarapwa nepembrolizumab vakapindura. Iyi subtype yekenza yemudumbu inokwana makumi maviri neshanu muzana yevarwere vese vegomarara uye inokodzera kuenderera mberi nekudzidza. Chekupedzisira, ma parameter anoongorora mhedzisiro yeiyi gastric cancer cancer immunotherapy kiriniki yekuyedza inodawo kunyatso fungidzirwa Chiyero chevarwere vakawana kuregererwa kwezvirwere muKeynote-22 kutongwa kwaive kudiki pane kweiyo RAINBOW kuyedzwa ne paclitaxel uye yakasanganiswa ramolizumab. Muchokwadi, iyo Keynote-012 bvunzo haina kunaka kubva patsananguro yehuwandu chete. Varwere vakapindura kurapwa havana kuratidza kukura kukuru mukufambira mberi-kwemahara kupona uye kupona kwese. Mune ramangwana, kuenderera mberi kwemakiriniki miedzo inodawo kuteerera kune idzi nyaya.
Kliniki miedzo ine chekuita neanti-CTLA-4 uye anti-PD-1 kurapwa kwave kwakabudirira kwazvo mu melanoma. Mukuenzanisa, mhedzisiro yekutongwa kweKeynote-012 inoita kunge ine tariro. Nekudaro, huwandu hwevanhu vanofa pagore regomarara repasi rose hwakapetwa katatu pane hwehutachiona hwemelanoma, saka mhedzisiro yechidzidzo ichi ichiri yakakosha. Kune vazhinji varwere vegomarara remudumbu vasina kurapwa kwakanaka, izvozvi zviwanikwa iri danho rekutanga rinonakidza mukuzadzikisa kuregererwa kwechirwere kwenguva refu. Mumakore achangopfuura, mukurumbira weemunotherapy mumunda we oncology iri kuramba ichikwira. Lancet Oncol akaburitsa iyo mhedzisiro mhedzisiro yeKeynote-012 kudzidza kuongorora kushanda kwePD-L1 inhibitor pembrolizumab mune varwere vane gomarara repamusoro remudumbu muna Chivabvu 3, izvo zvakakwezva kutarisisa. Nyanzvi Elizabeth C Smyth weRoyal Marsden Hospital muEngland akadudzira chidzidzo ichi, izvo zvinogona kutiunzira dzimwe pfungwa nekurudziro.
Kufungidzira kwekenza yemudumbu yepamusoro kwakashomeka, uye isingasviki 10-15% yevarwere ve metastatic vanogona kurarama kweanopfuura makore maviri. Trastuzumab uye ramoluzumab yechipiri-mutsara kurapwa kweHER2-inovhenekera gastric kenza varwere vanogona zvishoma kuvandudza kupona kwese. Nekuti pane mienzaniso mizhinji yekundikana kwemishonga yekurapa mumunda wekenza yemudumbu, zvinoita sekunge mishonga iyi yakawana budiriro shoma. Mune ino yakaoma mamiriro eazvino epamberi gomarara yekurapa kurapwa, iyo Keynote-2 yekudzidza yakaitwa naPurofesa Kei Muro uye vaaishanda navo pakutanga vakaratidza mhedzisiro, zvichiratidza kuti PD-L012 inhibitors ine mukana wekurapa kukosha mune yakakwira gastric cancer.
Zvabuda zveKeynote-012 kudzidza zvinoshamisa
Muchidzidzo cheKeynote-012, varwere vePD-L1-vane chirwere chegomarara repamberi vakagamuchira anti-PD-1 antibody pembrolizumab kusvika pakukura kwechirwere kana zviitiko zvisinga tsindike. Chidzidzo ichi chakaongorora huwandu hwevarwere zana nemakumi mapfumbamwe nemaviri vane gomarara repamberi remudumbu, iro 162 (65%) yaive netarisiro yePD-L40, uye pakupedzisira 1 (39%) varwere vakanyoreswa mune ino yepasi rose multicenter Phase 24B kudzidza. Zvinofadza, 1 yevarwere makumi matatu nevaviri (17%) vakasangana neremarara regression; 32 ye53 (8%) varwere vane hunovhenekerwa hunoshanda vakasimbisa kuregererwa zvishoma. Iyi yekuregererwa mwero inoenderana nemhedzisiro yemununotherapy miedzo mune mamwe kanzira, ine nguva yepakati yekupindura kwemasvondo makumi mana, uye 36 yevarwere makumi matatu nevatatu (22%) vane kuregererwa kwechirwere havana kuratidza kukura kwechirwere senge yenguva yekubika. Sezvinotarisirwa, 40 varwere (4%) vakasangana nezviitiko zvakasangana zvine chekuita nemuviri. Hapana varwere vakasiya kurapwa nekuda kwezviitiko zvakashata zvine chekuita ne immune. Zvichienzaniswa ne36% kusvika 11% yevarwere mune yechipiri-mutsara chemotherapy kutongwa, mhedzisiro yacho yakashamisa kwazvo. Tichifunga nezve chokwadi chekuti mhedzisiro yekupona yazvino gomarara repasi rose gastric kiriniki miedzo inokanganiswa nemisiyano yedunhu, Kei Muro nevamwe vaaishanda navo zvakaratidza zvakare kuti kupona kwevarwere veAsia nevasiri veAsia mukutongwa kweKeynote-9 kwakafanana.
Ko kutaura kwePD-L1 kunogona kufanotaura kushanda kwemununotherapy?
Keynote-012 bvunzo yekuongorora inoshandisa immunohistochemistry kuti ione kutaura kwePD-L1. Varwere vane tumarara maseru, maseru ekudzivirira kana aya maviri maseru maseru vanofanirwa kuratidza angangoita 1% yePD-L1 kuti vakwanise kutongwa. Munyori akabva aongororazve chimiro chePD-L1 achishandisa assays dzakasiyana. Mhedzisiro yechipiri assay inoratidza kuti kutaura kwePD-L1 mumasero ekudzivirira muviri, kwete maseru emota, kunoenderana nekushanda kwepembrolizumab mukenza yemudumbu. Kechipiri, masere makumi matatu nemakumi matatu nemashanu ebhaopsy mienzaniso inogona kuongororwa yaive neyakaipa PD-L8 mhedzisiro. Mhedzisiro iyi inoratidza kuomarara kwePD-L35 kuongorora zvakanyanya, kunyanya kuongororwa kwema biomarkers ekenza yemudumbu. Uku kutsauka kunogona kunge kuri nekuda kweshanduko ine simba muPD-L1 kutaura mushure mekurapwa, mutsauko munzira dzekuongorora, uye heterogeneity yegomarara repamuviri. Naizvozvo, hazvizivikanwe kana mumakiriniki epfuura akaedzwa pasina biomarker kuongorora, vamwe varwere vane zvinoita kunge PD-L1 yakaipa varwere vakagashira anti-PD1 mishonga yekurapa kwekuregererwa kwechirwere vaive nehukama nehunhu hwekutaura kwebiomarker, Kana kana paine kuwirirana chaiko. pakati biomarkers uye kushanda. Kuwedzera kutsvagurudza kunodiwa
Nzira yakanakisa yekutarisa PD-L1 kutaura uye kuti ichokwadi here uye inoshanda yekufungidzira biomarker mune gastric cancer cancer. Vanyori vanotaurawo mhedzisiro yekutanga yeiyo interferon gamma gene expression seye biomarker yepuru tishu lesion yakazvimirira kufanotaura. Kana uyu mhedzisiro yakaverengerwa, zvinogona kubatsira kudzivirira mamwe matambudziko ane chekuita neyemunohistochemistry mune ramangwana.
Nyaya dzinoda kumberi kufunga
Ehe, bvunzo diki yemuenzaniso senge Keynote-012 zvinonzwisisika ine mamwe matambudziko. Kutanga, hazvizivikanwe kana paine kudyidzana pakati pemakemikari akagashirwa kare uye kushanda kwepembrolizumab. Kunyangwe vamwe vanopindura varwere vanga vangogamuchira yekutanga-mutsara kana mashoma chemotherapy pamberi pembrolizumab, vazhinji (63%) vanopindura varwere vanga vagamuchira wechipiri-mutsara kana kupfuura anti-bundu kurapwa. Zvakare, Keynote-012 idiki sampuro yekutanga kiriniki miedzo uye haigone kuverengerwa muvazhinji varwere vane gomarara repamberi remudumbu nekupona pfupi, izvo zvinogona kuita immunotherapy-zvine hukama neinononoka kupindura mitengo uye dzimwe nguva manyepo.
Mhedzisiro yekufambira mberi haina kugutsikana. Akawanda anoenderera mberi emakiriniki miedzo ari kuyedza kuona yakanakisa immunotherapy nguva hwindo yevarwere vegomarara remudumbu. Chechipiri, kunyangwe mune fungidziro, varwere vane gomarara remudumbu vane microsomes isina kugadzikana vanofanirwa kuve vanokodzera immunotherapy, uye
MuKeynote-012 kuyedza, chete hafu yevarwere vane microsatellite kusagadzikana kwakarapwa nepembrolizumab vakapindura. Iyi subtype yekenza yemudumbu inokwana makumi maviri neshanu muzana yevarwere vese vegomarara uye inokodzera kuenderera mberi nekudzidza. Chekupedzisira, ma parameter anoongorora mhedzisiro yeiyi gastric cancer cancer immunotherapy kiriniki yekuyedza inodawo kunyatso fungidzirwa Chiyero chevarwere vakawana kuregererwa kwezvirwere muKeynote-22 kutongwa kwaive kudiki pane kweiyo RAINBOW kuyedzwa ne paclitaxel uye yakasanganiswa ramolizumab. Muchokwadi, iyo Keynote-012 bvunzo haina kunaka kubva patsananguro yehuwandu chete. Varwere vakapindura kurapwa havana kuratidza kukura kukuru mukufambira mberi-kwemahara kupona uye kupona kwese. Mune ramangwana, kuenderera mberi kwemakiriniki miedzo inodawo kuteerera kune idzi nyaya.
Kliniki miedzo ine chekuita neanti-CTLA-4 uye anti-PD-1 kurapwa kwave kwakabudirira kwazvo mu melanoma. Mukuenzanisa, mhedzisiro yekutongwa kweKeynote-012 inoita kunge ine tariro. Nekudaro, huwandu hwevanhu vanofa pagore regomarara repasi rose hwakapetwa katatu pane hwehutachiona hwemelanoma, saka mhedzisiro yechidzidzo ichi ichiri yakakosha. Kune vazhinji varwere vegomarara remudumbu vasina marapiro anoshanda, izvozvi zviwanikwa iri danho rekutanga rinonakidza mukuzadzikisa kuregererwa kwechirwere kwenguva refu.
