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San Antonio Breast Cancer Symposium (SABCS) 2021. Cancro al seno triplo Negativo, nuovi dati sul promettente ADC Datopotamab Deruxtecan confermano risposta duratura e controllo della malattia

Nuovi promettenti dati dalla coorte TNBC dello studio di fase 1 TROPION-PanTumor01 del datopotamab deruxtecan di Daiichi Sankyo e AstraZeneca sono stati presentati al SABCS2021.

Tokyo, Monaco e Basking Ridge, 10 dicembre 2021- Datopotamab deruxtecan (Dato-DXd), un anticorpo monoclonale farmaco-coniugato (ADC) DXd anti-TROP2 sviluppato da Daiichi Sankyo e AstraZeneca, continua a mostrare risposta tumorale duratura e controllo della malattia nelle pazienti affette da carcinoma mammario triplo negativo (TNBC) metastatico con progressione della malattia dopo trattamento standard. I dati incoraggianti della coorte TNBC dello studio di fase 1 TROPION-PanTumor01 sono stati oggetto di una presentazione orale al San Antonio Breast Cancer Symposium 2021 (#SABCS21).

Il carcinoma mammario triplo negativo rappresenta circa il 10-15% dei casi di cancro al seno ed è associato a una maggiore recidiva della malattia e a una prognosi peggiore rispetto ad altri sottotipi di cancro al seno. [i],[ii],[iii] Si stima che solo il 12,2% dei pazienti con TNBC metastatico alla diagnosi riesca a sopravvivere fino a cinque anni e la sopravvivenza globale mediana è generalmente inferiore a due anni. .2,3

Un tasso di risposta obiettiva (ORR) del 34% è stato osservato in 15 delle 44 pazienti trattate con datopotamab deruxtecan (6 mg/kg [n=42] e 8 mg/kg [n=2]) come valutato dalla revisione centrale indipendente in cieco. Quattordici risposte complete/parziali confermate (CR/PR) con un'ulteriore CR/PR in attesa di conferma e malattia stabile in altre 17 pazienti sono state riportate dopo un follow-up mediano di 7,6 mesi (range, 4 - 13 mesi). La durata mediana della risposta (DOR) non è stata raggiunta (range, 2,7 - 7,4+ mesi), con la maggior parte delle risposte in atto al cut-off dei dati del 30 luglio 2021. È stato osservato un tasso di controllo della malattia (DCR) del 77%.

In un sottogruppo di 27 pazienti con malattia misurabile e non precedentemente trattati con un ADC a base di inibitori della topoisomerasi I, è stato riportato un tasso di risposta obiettiva del 52% con datopotamab deruxtecan. Tredici CR/PR confermate con una ulteriore CR/PR in attesa di conferma e malattia stabile riportata in altre nove pazienti, dopo un follow-up mediano di 8,8 mesi (range, 4 - 13 mesi). Un tasso di controllo della malattia dell'81% è stato osservato in questo sottogruppo di pazienti.

"Nonostante i recenti progressi nel trattamento del carcinoma mammario triplo negativo, sussiste una significativa necessità di migliorare gli esiti per le pazienti, che sottolinea l'importanza di sviluppare terapie nuove ed efficaci - ha spiegato Ian E. Krop, MD, PhD, capo associato della divisione di oncologia senologica del Susan F. Smith Center for Women's Cancers, Dana Farber Cancer Institute - Questi risultati preliminari con datopotamab deruxtecan in pazienti pretrattate con carcinoma mammario triplo negativo metastatico sono molto incoraggianti e garantiscono ulteriori valutazioni di questo ADC anti-TROP2."

Il profilo di sicurezza complessivo di datopotamab deruxtecan nel TNBC osservato nello studio TROPION-PanTumor01 è risultato in linea con quanto riportato in precedenza senza nuovi segnali di sicurezza. Gli eventi avversi emergenti dal trattamento (TEAEs) verificatisi in ≥15% dei pazienti hanno incluso nausea, stomatite, vomito, affaticamento, alopecia, infiammazione delle mucose, stipsi, mal di testa, linfocitopenia, neutropenia, piressia, anemia, prurito, ipokaliemia, diarrea e tosse. TEAE di grado 3 o superiore legati al trattamento si sono verificati nel 23% dei pazienti. Non sono stati osservati casi di malattia polmonare interstiziale (ILD).

"Questi risultati aggiornati continuano a mostrare la promessa di datopotamab deruxtecan come strategia di trattamento durevole per le pazienti con cancro al seno triplo negativo precedentemente trattato, una forma di cancro al seno storicamente difficile da trattare. - Ha dichiarato Gilles Gallant, BPharm, PhD, FOPQ,  Vice Presidente Senior e Capo Globale dello Sviluppo Oncologico, del dipartimento R&D in Oncologia di Daiichi Sankyo - Siamo impegnati portare avanti lo sviluppo di datopotamab deruxtecan e a stabilire dove questo anti-TROP2 specificamente ingegnerizzato può essere più efficace nel trattamento del cancro al seno triplo negativo".

Le pazienti sono state trattate con una mediana di tre terapie precedenti nel setting metastatico (range, 1-10), compresi i taxani (91%), la chemioterapia a base di platino (52%), l'immunoterapia (43%), gli ADC a base di inibitori della topoisomerasi I (30%; sacituzumab govitecan, n=10; trastuzumab deruxtecan, n=2; patritumab deruxtecan, n=1) e gli inibitori PARP (16%). Al momento del cut-off dei dati, il 30 luglio 2021, il 30% delle pazienti risultava ancora in trattamento con datopotamab deruxtecan.