Bastano due farmaci?

Se i dati saranno confermati e in accordo con altre parti dello studio ALTTO, per le pazienti con un carcinoma primario HER2 ci potrebbe essere un nuovo standard di cura: la terapia neoadiuvante con una doppia inibizione appunto di HER2. Questo almeno è quanto lasciano prevedere i risultati dello studio neo ALTTO presentati alla San Antonio Breast Cancer Conference, in corso in questi giorni in Texas, da Martine Piccart-Gebhart, capo del Breast International Group di Bruxelles, che sta coordinando il lavoro.

Tra il 2008 e il 2010 sono state reclutate, in 86 centri di 23 paesi di tutto il mondo, 455 donne con un tumore HER2 positivo di diametro superiore ai due centimetri; tutte sono state randomizzate a ricevere lapatinib o trastuzumab o una combinazione di entrambi per 6 settimane; quindi paclitaxel per 12 settimane. A quel punto le donne sono state operate e in seguito trattate ancora con la chemioterapia adiuvante, seguita poi dalla stessa terapia che avevano assunto in fase neoadiuvante per un totale di 52 settimane.

L’end point finale è fissato a 10 anni, ma i primi risultati dicono che il 51,3% delle donne trattate con i due farmaci prima dell’intervento ha avuto una risposta patologica completa e che né nel loro tessuto mammario né nei loro linfonodi è stato possibile trovare cellule neoplastiche. Per confronto, la percentuale con un solo farmaco è stata pari al 29,5 con il trastuzumab e al 24,7% con il lapatinib.
Se l’andamento sarà confermato durante i dieci anni previsti e se i dati saranno in accordo anche con quelli della prima parte dello studio (ALTTO), almeno una parte delle donne con carcinoma mammario primario HER2 positivo potrebbe evitare il ricorso alla chirurgia e avere una risposta piena con la sola terapia mirata.

Lo studio, inoltre, costituisce uno dei primi esempi di collaborazioni (per quanto indiretta, in questo caso) che con ogni probabilità saranno sempre più frequenti in futuro: i ricercatori sono infatti stati sostenuti economicamente sia da Roche, che produce il trastuzumab, sia da GlaxoSmithKline, che produce il lapatinib.

Fonte
www.aacr.org/home/public–media/aacr-in-the-news.aspx?d=3230

Publication Number: S1-01
Presenter: Martine Piccart-Gebhart, M.D., Ph.D.

Title:
The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06)

Authors: Martine Piccart-Gebhart1, Andrew P Holmes2, Evandro de Azambuja3, Serena Di Cosimo4, Ramona Swaby5, Michael Untch6, Christian Jackisch7, Istvan Lang8, Ian Smith9, Frances Boyle10, Binghe Xu11, Carlos Barrios12, Richard Gelber13, Holger Eidtmann14 and José Baselga15. 1Jules Bordet Institute, Brussels, Belgium; 2Frontier Science (Scotland) Ltd, Kincraig, Kingussie, United Kingdom; 3Jules Bordet Institute, Brussels, Belgium; 4Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 5GlaxoSmithKline; 6Academic Hospital of the University Charite, Germany; 7Klinikum Offenbach, Germany; 8National Institute of Oncology, Hungary; 9Royal Marsden Hospital and Institute of Cancer Research, London, United Arab Emirates; 10Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital North Sydney and University of Sydney, Australia; 11Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; 12PUCRS School of Medicine, Porto Alegre, Belgium; 13Dana-Farber Cancer Institute, Boston; 14University Hospital Kiel, Kiel, Germany and 15Memorial Sloan Kettering Cancer Center, New York.

Background: The NeoALTTO study demonstrated a significantly higher breast pathological complete response (pCR) rate (NSABP definition – ypT0/is) with dual HER2 blockade using lapatinib and trastuzumab compared with single HER2 blockade using either lapatinib or trastuzumab (51.3% vs. 24.7% vs. 29.5%, respectively; p< 0.01 for both) in HER2 positive primary breast cancer (BC). A similar pattern was seen for locoregional pCR (ypT0/is ypN0) (Baselga J et al. Lancet 2012).

Material and Methods: From January, 2008, to December, 2009, 455 patients were randomized from 99 participating sites in 23 countries. Patients were randomized to receive mg/kg IV loading dose followed by 2 mg/kg IV weekly (149 pts), or lapatinib 1000 mg/d with trastuzumab for a total of 6 weeks (152 pts). After this biological window, patients continued on the same targeted therapy plus weekly paclitaxel 80 mg/m² for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). After surgery, patients received 3 cycles of adjuvant FEC followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy), with on-going follow-up planned until 10 years after last randomised patient. Secondary objectives included disease-free survival and overall survival (OS). Following current practice and draft FDA recommendations for neoadjuvant trial endpoints, an amendment was made to the protocol secondary objectives (released in May 2013). DFS (from surgery) was replaced by event-free survival (EFS) from randomisation; OS from surgery was correspondingly replaced with OS from randomisation, and examination of the association between these survival endpoints and locoregional pCR (ypT0/is ypN0) was added as a secondary objective. EFS was defined as the time from randomization to first EFS event (breast cancer relapse, second primary malignancy or death without recurrence). OS was defined as the time from randomization to death from any cause.

Results:
The clinical cut-off date for the first planned analysis of these secondary objectives was on 26 May 2013, three years after the date of last surgery. Data cleaning is ongoing and analysis will be completed by November 2013. Results for EFS, OS and their association with pCR will be presented at the meeting.

Fuding: GlaxoSmithKline is the sponsor of this trial.