Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma: final results of the randomised phase II ImmunoCobiVem trial
Background - Optimal sequencing of immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) in BRAFV600-positive advanced melanoma should achieve rapid tumour control and durable progression-free survival (PFS), translating into prolonged overall survival (OS). - Patients and methods - The 1...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 2025
|
| In: |
ESMO open
Year: 2025, Jahrgang: 10, Heft: 5, Pages: 1-12 |
| ISSN: | 2059-7029 |
| DOI: | 10.1016/j.esmoop.2025.105053 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.esmoop.2025.105053 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2059702925009226 
|
| Verfasserangaben: | E. Livingstone, H. J. Gogas, L. Kandolf, F. Meier, T. K. Eigentler, M. Ziemer, P. Terheyden, A. Gesierich, R. A. Herbst, K. C. Kähler, D. C. Ziogas, Ž. Mijušković, M. Garzarolli, C. Garbe, A. Roesch, S. Ugurel, R. Gutzmer, C. Gaudy-Marqueste, F. Kiecker, J. Utikal, M. Hartmann, S. Miethe, S. Eckhardt, L. Zimmer, D. Schadendorf |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1934907995 | ||
| 003 | DE-627 | ||
| 005 | 20250901095747.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250828s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.esmoop.2025.105053 |2 doi | |
| 035 | |a (DE-627)1934907995 | ||
| 035 | |a (DE-599)KXP1934907995 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Livingstone, Elisabeth |e VerfasserIn |0 (DE-588)1049231325 |0 (DE-627)781379636 |0 (DE-576)403194016 |4 aut | |
| 245 | 1 | 0 | |a Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma |b final results of the randomised phase II ImmunoCobiVem trial |c E. Livingstone, H. J. Gogas, L. Kandolf, F. Meier, T. K. Eigentler, M. Ziemer, P. Terheyden, A. Gesierich, R. A. Herbst, K. C. Kähler, D. C. Ziogas, Ž. Mijušković, M. Garzarolli, C. Garbe, A. Roesch, S. Ugurel, R. Gutzmer, C. Gaudy-Marqueste, F. Kiecker, J. Utikal, M. Hartmann, S. Miethe, S. Eckhardt, L. Zimmer, D. Schadendorf |
| 246 | 3 | 3 | |a Early switch from run-in with targeted to immunotherapy in advanced BRAF V600 -positive melanoma$dfinal results of the randomised phase II ImmunoCobiVem trial |
| 264 | 1 | |c May 2025 | |
| 300 | |b Illustrationen | ||
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 8. Mai 2025, Artikelversion: 8. Mai 2025 | ||
| 500 | |a V600 ist im Titel hochgestellt | ||
| 500 | |a Gesehen am 28.08.2025 | ||
| 520 | |a Background - Optimal sequencing of immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) in BRAFV600-positive advanced melanoma should achieve rapid tumour control and durable progression-free survival (PFS), translating into prolonged overall survival (OS). - Patients and methods - The 1 : 1 randomised phase II ImmunoCobiVem trial compared—after a 3-month run-in phase with vemurafenib (VEM, 960 mg twice daily) and cobimetinib (COB, 60 mg daily days 21-28, q4w)—continuous VEM + COB until disease progression (PD1) and second-line atezolizumab (ATEZO, 1200 mg, q3w) in arm A versus early switch to ATEZO after run-in, followed by crossover to VEM + COB at PD1, in arm B. PFS from the start of run-in until PD1 was the primary endpoint (PFS1); secondary efficacy endpoints were OS, overall PFS (PFS2) and PFS3 (time from PD1 to PD after crossover, i.e. PD2) and best overall response rates (BORRs). - Results - The final analysis (median follow-up 57.0 months, interquartile range 22.7-63.0 months) confirmed longer PFS1 for continuous TT [arm A (69 patients) versus arm B (early switch, 66 patients); hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.91, P = 0.006], but early switch to ICIs resulted in better long-term OS [4- and 5-year landmark OS 42% (95% CI 29% to 55%) and 40% (95% CI 27% to 53%) for arm A, and 53% (95% CI 38% to 65%) and 45% (95% CI 31% to 58%) for arm B; descriptive HR 1.17, 95% CI 0.71-1.91]. Absolute BORRs were 81% and 89%, respectively, with 15 (22%) and 19 (29%) patients achieving a complete response at least once along each sequence. At crossover, TT retreatment (arm B) resulted in higher PFS3 than second-line ICI (arm A). - Conclusions - Early switch to ICIs after TT run-in (arm B) led to an improved, although not statistically significant, 4- and 5-year landmark OS compared with arm A. No subgroups were identified for which a TT run-in provided clinical benefit. The number of patients developing brain metastasis and the time to brain metastasis were not improved by an early TT to ICI switch. | ||
| 650 | 4 | |a crossover design | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a melanoma | |
| 650 | 4 | |a sequential therapy | |
| 650 | 4 | |a targeted therapy | |
| 700 | 1 | |a Gogas, H. J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kandolf, L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meier, F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eigentler, T. K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ziemer, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Terheyden, P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gesierich, A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herbst, R. A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kähler, K. C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ziogas, D. C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mijušković, Ž. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garzarolli, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garbe, C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roesch, A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ugurel, S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gutzmer, R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gaudy-Marqueste, C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kiecker, F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Utikal, Jochen |d 1974- |e VerfasserIn |0 (DE-588)1026463750 |0 (DE-627)726765015 |0 (DE-576)371816580 |4 aut | |
| 700 | 1 | |a Hartmann, M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Miethe, S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eckhardt, S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zimmer, L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schadendorf, Dirk |d 1960- |e VerfasserIn |0 (DE-588)11142576X |0 (DE-627)499566076 |0 (DE-576)289702275 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ESMO open |d [London] : Elsevier, 2016 |g 10(2025), 5, Artikel-ID 105053, Seite 1-12 |h Online-Ressource |w (DE-627)84705344X |w (DE-600)2844985-X |w (DE-576)454658516 |x 2059-7029 |7 nnas |a Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma final results of the randomised phase II ImmunoCobiVem trial |
| 773 | 1 | 8 | |g volume:10 |g year:2025 |g number:5 |g elocationid:105053 |g pages:1-12 |g extent:12 |a Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma final results of the randomised phase II ImmunoCobiVem trial |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.esmoop.2025.105053 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S2059702925009226 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20250828 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 11142576X |a Schadendorf, Dirk |m 11142576X:Schadendorf, Dirk |d 50000 |e 50000PS11142576X |k 0/50000/ |p 25 |y j | ||
| 998 | |g 1026463750 |a Utikal, Jochen |m 1026463750:Utikal, Jochen |d 60000 |e 60000PU1026463750 |k 0/60000/ |p 20 | ||
| 999 | |a KXP-PPN1934907995 |e 4765094804 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"physDesc":[{"extent":"12 S.","noteIll":"Illustrationen"}],"name":{"displayForm":["E. Livingstone, H. J. Gogas, L. Kandolf, F. Meier, T. K. Eigentler, M. Ziemer, P. Terheyden, A. Gesierich, R. A. Herbst, K. C. Kähler, D. C. Ziogas, Ž. Mijušković, M. Garzarolli, C. Garbe, A. Roesch, S. Ugurel, R. Gutzmer, C. Gaudy-Marqueste, F. Kiecker, J. Utikal, M. Hartmann, S. Miethe, S. Eckhardt, L. Zimmer, D. Schadendorf"]},"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedDisp":"May 2025","dateIssuedKey":"2025"}],"language":["eng"],"note":["Online verfügbar: 8. Mai 2025, Artikelversion: 8. Mai 2025","V600 ist im Titel hochgestellt","Gesehen am 28.08.2025"],"id":{"doi":["10.1016/j.esmoop.2025.105053"],"eki":["1934907995"]},"title":[{"subtitle":"final results of the randomised phase II ImmunoCobiVem trial","title":"Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma","title_sort":"Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma"}],"relHost":[{"recId":"84705344X","pubHistory":["1.2016 -"],"corporate":[{"roleDisplay":"Herausgebendes Organ","role":"isb","display":"European Society for Medical Oncology"}],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"periodical"},"origin":[{"publisher":"Elsevier ; BMJ","publisherPlace":"[London] ; London","dateIssuedKey":"2016","dateIssuedDisp":"2016-"}],"part":{"text":"10(2025), 5, Artikel-ID 105053, Seite 1-12","issue":"5","volume":"10","extent":"12","year":"2025","pages":"1-12"},"name":{"displayForm":["European Society for Medical Oncology"]},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"ESMO open","title_sort":"ESMO open","subtitle":"cancer horizons"}],"id":{"zdb":["2844985-X"],"eki":["84705344X"],"issn":["2059-7029"]},"disp":"Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma final results of the randomised phase II ImmunoCobiVem trialESMO open","note":["Gesehen am 13.06.24"]}],"person":[{"family":"Livingstone","roleDisplay":"VerfasserIn","display":"Livingstone, Elisabeth","role":"aut","given":"Elisabeth"},{"role":"aut","display":"Gogas, H. J.","given":"H. J.","roleDisplay":"VerfasserIn","family":"Gogas"},{"display":"Kandolf, L.","role":"aut","given":"L.","family":"Kandolf","roleDisplay":"VerfasserIn"},{"family":"Meier","roleDisplay":"VerfasserIn","given":"F.","role":"aut","display":"Meier, F."},{"roleDisplay":"VerfasserIn","family":"Eigentler","display":"Eigentler, T. K.","role":"aut","given":"T. K."},{"given":"M.","role":"aut","display":"Ziemer, M.","family":"Ziemer","roleDisplay":"VerfasserIn"},{"given":"P.","role":"aut","display":"Terheyden, P.","family":"Terheyden","roleDisplay":"VerfasserIn"},{"family":"Gesierich","roleDisplay":"VerfasserIn","display":"Gesierich, A.","role":"aut","given":"A."},{"family":"Herbst","roleDisplay":"VerfasserIn","given":"R. A.","role":"aut","display":"Herbst, R. A."},{"given":"K. C.","display":"Kähler, K. C.","role":"aut","family":"Kähler","roleDisplay":"VerfasserIn"},{"family":"Ziogas","roleDisplay":"VerfasserIn","display":"Ziogas, D. C.","role":"aut","given":"D. C."},{"family":"Mijušković","roleDisplay":"VerfasserIn","given":"Ž.","role":"aut","display":"Mijušković, Ž."},{"family":"Garzarolli","roleDisplay":"VerfasserIn","given":"M.","display":"Garzarolli, M.","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Garbe","given":"C.","role":"aut","display":"Garbe, C."},{"family":"Roesch","roleDisplay":"VerfasserIn","given":"A.","role":"aut","display":"Roesch, A."},{"family":"Ugurel","roleDisplay":"VerfasserIn","display":"Ugurel, S.","role":"aut","given":"S."},{"roleDisplay":"VerfasserIn","family":"Gutzmer","given":"R.","display":"Gutzmer, R.","role":"aut"},{"family":"Gaudy-Marqueste","roleDisplay":"VerfasserIn","given":"C.","display":"Gaudy-Marqueste, C.","role":"aut"},{"given":"F.","role":"aut","display":"Kiecker, F.","roleDisplay":"VerfasserIn","family":"Kiecker"},{"roleDisplay":"VerfasserIn","family":"Utikal","given":"Jochen","display":"Utikal, Jochen","role":"aut"},{"role":"aut","display":"Hartmann, M.","given":"M.","roleDisplay":"VerfasserIn","family":"Hartmann"},{"given":"S.","role":"aut","display":"Miethe, S.","roleDisplay":"VerfasserIn","family":"Miethe"},{"roleDisplay":"VerfasserIn","family":"Eckhardt","display":"Eckhardt, S.","role":"aut","given":"S."},{"family":"Zimmer","roleDisplay":"VerfasserIn","role":"aut","display":"Zimmer, L.","given":"L."},{"family":"Schadendorf","roleDisplay":"VerfasserIn","given":"Dirk","role":"aut","display":"Schadendorf, Dirk"}],"titleAlt":[{"title":"Early switch from run-in with targeted to immunotherapy in advanced BRAF V600 -positive melanoma$dfinal results of the randomised phase II ImmunoCobiVem trial"}],"recId":"1934907995"} | ||
| SRT | |a LIVINGSTONEARLYSWITC2025 | ||