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Tumore al polmone, inizia la sperimentazione di trastuzumab deruxtecan come terapia di prima linea per il carcinoma polmonare non a piccole cellule metastatico con mutazione HER2

L'attuale standard di trattamento di prima linea dei pazienti con NSCLC HER2 mutato non resecabile, localmente avanzato o metastatico è l'immunoterapia PD-1 o PD-L1, con o senza chemioterapia a base di platino, tuttavia dal 40% al 60% dei tumori non risponde al trattamento iniziale e continua a progredire. Dopo la risposta robusta e duratura ottenuta nello studio DESTINY -LUNG01 dall’ADC trastuzumab deruxtecan nei pazienti affetti da questo tipo di carcinoma, Daiichi Sankyo e Astrazeneca iniziano la sperimentazione di ENHERTU come potenziale terapia di prima linea nel trial head-to-head di fase 3 DESTINY-LUNG04.

Tokyo, Monaco e Basking Ridge, 23 dicembre 2021 -  Con la somministrazione al primo paziente, Daiichi Sankyo annuncia l’inizio dello  studio globale di fase 3 DESTINY-Lung04, il trial che valuta l'efficacia e la sicurezza dell’anticorpo monoclonale coniugato ENHERTU® (trastuzumab deruxtecan), come trattamento di prima linea dei pazienti affetti da carcinoma polmonare non a piccole cellule (NSCLC) non resecabile, localmente avanzato o metastatico, con mutazione HER2. L’ADC anti-HER2 trastuzumab deruxtecan è sviluppato congiuntamente da  Daiichi Sankyo e AstraZeneca ed è attualmente in sperimentazione per il trattamento di vari tumori che esprimono HER2, inclusi il carcinoma mammario, gastrico, polmonare e colorettale.

Il carcinoma polmonare è la principale causa di morte per cancro, ed è responsabile di circa 1/5 di tutti i decessi per cancro. L’NSCLC corrisponde a circa l’80-85% di tutti i carcinomi al polmone. [i],[ii],[iii] Attualmente non ci sono farmaci approvati specificamente per il trattamento del NSCLC con mutazione HER2, che colpisce circa il 2% - 4% dei pazienti con NSCLC non squamoso. [iv],[v]

L'attuale standard di cura nel trattamento di prima linea dei pazienti con NSCLC e mutazione HER2 è l'immunoterapia con farmaci anti-PD-1 o PD-L1 con o senza chemioterapia a base di platino.[vi] Mentre questi regimi di trattamento possono migliorare la sopravvivenza, almeno dal 40% al 60% dei tumori non risponde al trattamento iniziale e si verifica una progressione della malattia. [vii],[viii],[ix],[x],[xi]

DESTINY-Lung04 è il primo studio di confronto testa a testa nel NSCLC che valuta ENHERTU come trattamento di prima linea rispetto allo standard di cura (chemioterapia con platino-pemetrexed in combinazione con pembrolizumab) in pazienti con NSCLC non-squamoso non resecabile, localmente avanzato o metastatico, che presenta mutazione di HER2 nell’esone 19 o 20.

"I risultati visti nello studio DESTINY-Lung01 hanno mostrato una risposta tumorale robusta e durevole in pazienti precedentemente trattati per carcinoma polmonare metastatico non a piccole cellule con mutazione  HER2. - Ha dichiarato Gilles Gallant, BPharm, PhD, FOPQ, Vice Presidente Senior, e capo globale della divisione di Sviluppo Oncologico del dipartimento R&D in Oncologia di Daiichi Sankyo - Sulla base di questi risultati promettenti, stiamo conducendo il trial DESTINY-Lung04 per valutare il potenziale di ENHERTU come prima linea di terapia in questa popolazione di pazienti".

Riferimenti

[I] World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed September 2021.

[II] ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Accessed September 2021.

[III] Cheema PK, et al. Curr Oncol. 2019;26(1):37-42.

[IV] Liu S, et al. Clin Cancer Res. 2018;24(11):2594-2604.

[V] Campbell JD, et al. Nat Genet. 2016 Jun;48(6):607-16.

[VI] Planchard D, et al. ESMO Clinical Practice Guidelines. 2020.

[VII] Man J, et al. JNCI Cancer Spectrum. 2021;5(3):pkab012.

[VIII] Paz-Ares L, et al. J Thorac Oncol. 2020 Oct;15(10):1657-1669.

[IX] Mok TSK, et al. Lancet. 2019 May 4;393(10183):1819-1830.

[X] Rodríguez-Abreu D et al. Ann Onc. 2021 Jul;32(7):881-895.

[XI] Brahmer J.R. et al. KEYNOTE-024 5-year OS update. ESMO 2021 Virtual Congress; Abstract LBA51.

[XII] Stephens P, et al. Nature. 2004;431:525-6.

[XIII] Mazières J, et al. J Clin Oncol. 2013;31:1997-2003.

[XIV] Arcila ME, et al. Clin Cancer Res. 2012;18:4910-8.

[XV] Pillai RN, et al. Cancer. 2017;123:4099-105.

[XVI] Offin M, et al. Cancer. 2019;125:4380-7.

[XVII] Ou S-HI, et al. J Clin Oncol. 2019;37(15 Suppl):9063.

[XVIII] Wei XW, et al. Thorac Cancer. 2020;11(6): 1512-21.

[XIX] Robichaux et al. Cancer Cell. 2019 Oct 14; 36(4): 444–457.e7.

[XX] Zhou J, et al. Ther Adv Med Oncol. 2020;12.