Aggiornamenti scientifici di NAB-paclitaxel nel MBC in terapia di combinazione

Studi con Abraxane in combinazione con schedula settimanale: dati di efficacia e tollerabilità Jackisch C et al., Breast Care (Basel). 2012 Apr;7(2):137-143

Phase II Trial of Weekly NAB-paclitaxel in Combination With Gemcitabine in Patients With Metastatic Breast Cancer V. Roy, B. R. LaPlant, G. G. Gross, C. L. Bane, F. M. Palmieri, on behalf of the North Central Cancer Treatment Group Roy V et al. Ann Oncol. 2009;20(3):449-453.

NAB-paclitaxel più gemcitabina: disegno dello studio This was an open-label, multicenter phase II study conducted through the North Central Cancer Treatment Group NAB-Paclitaxel 125 mg/m2 Days 1 and 8 every 21 days Gemcitabine 1000 mg/m2 Days 1 and 8 every 21 days IV, intravenous; MBC, metastatic breast cancer. Roy V et al. Ann Oncol. 2009;20(3):449-453. 4

NAB-paclitaxel più gemcitabina: efficacia del trattamento di prima linea nelle donne con MBC Outcome (N = 50) Value Number of administered cycles, median (range) 7 (1-17) ORRa (≥ PR), n (%; 95% CI) 25 (50; 36-64) CR, n (%) 4 (8) PR, n (%) 20 (42) Duration of response in months, median (95% CI) 6.9 (5.7, NR) PFS in months, median (95% CI) 7.9 (5.4-10) OS in months, median (95% CI) NR 6-month PFS, % (95% CI) 60 (48-76) 6-month OS, % (95% CI) 92 (85-100) a Overall confirmed response. CI, confidence interval; CR, complete response; MBC, metastatic breast cancer; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response. Roy V et al. Ann Oncol. 2009;20(3):449-453. 5

52 16 MA 1219 00004773 2007 04 26 - 03:46:51 PM ESA 1256 2007 10 01 - 12:05:26 PM 69 21 Phase II Multicenter Trial of NAB-paclitaxel and Capecitabine in First-Line Treatment of Patients with Metastatic Breast Cancer Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93 Reviewed and Approved by External Scientific Affairs: Slide Deck ID - ESA 1256 - October 2007

NAB-paclitaxel e capecitabina: disegno dello studio Purpose: A single arm, multi-center phase II trial to determine efficacy of NAB-Paclitaxel + capecitabine as first line treatment of MBC patients (HER2-) N = 50 Patients with ECOG PS 0-2, HER2-, adequate organ function Cycles of 21 days until disease progression or dose-limiting toxicity NAB-paclitaxel 125 mg/m2 IV over 30 min Days 1 and 8 q3w without premedication Capecitabine 825 mg/m2 Orally bid Days 1-14 q3w Endpoints Primary: ORR Secondary: PFS, OS, safety bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks. Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93

NAB-paclitaxel e capecitabina: tassi di risposta Outcome (N = 46) n (%) ORR CR PR 28 (61) 2 (4) 26 (57) SD 10 (22) PD 8 (17) Note: 4 of the 50 patients not evaluable for response. CR, complete response; MBC, metastatic breast cancer; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease. Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93

NAB-paclitaxel e capecitabina: Progression Free Survival The red line indicates product limit estimate of survival curve and circles indicate a censored observation Schwartzberg et al. Clin Breast Cancer. 2012 Apr;12(2):87-93

NAB-paclitaxel e capecitabina: Overall Survival The red line indicates product limit estimate of survival curve and circles indicate a censored observation

NAB-paclitaxel e lapatinib nel MBC HER2+: risultati

NAB-paclitaxel e lapatinib nel MBC HER2+: risultati

STUDIO GOIM NAB-paclitaxel e Capecitabina in MBC

6 cicli (+ 2 a discrezione del clinico) STUDIO GOIM - NAB-paclitaxel e capecitabina in MBC - Disegno dello studio A MULTICENTER PHASE II TRIAL OF NAB-PACLITAXEL AND CAPECITABINE AS FIRST LINE TREATMENT IN HER-2 NEGATIVE METASTATIC BREAST CANCER (MBC) N = fino a 94 Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo 6 cicli (+ 2 a discrezione del clinico) nab paclitaxel 150 mg/m2 IV in 30 min GG 1 e 8 q3w senza premedicazione Capecitabina 825 mg/m2 Orale 2 volte al giorno GG 1-14 q3w Endpoints Primario: ORR, PFS Secondari: OS, safety bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks. EUDRACT 000393-35

Phase II Trial of Weekly NAB-paclitaxel With Carboplatin and Trastuzumab as First-Line Therapy for Women With HER2-Overexpressing Metastatic Breast Cancer K. Conlin, A. D. Seidman, A. Bach, D. Lake, M. Dickler, G. D’Andrea, T. Traina, M. Danso, A. M. Brufsky, M. Saleh, A. Clawson, C. A. Hudis Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.

NAB-paclitaxel, carboplatino e trastuzumab nel MBC HER2+: schema terapeutico AUC, area under the curve; HER2, human epidermal growth factor receptor2; MBC, metastatic breast cancer; wk, week. Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.

NAB-paclitaxel, carboplatino e trastuzumab nel MBC HER2+: risultati di efficacia Confirmed responses (N = 32) Value ORR (CR + PR), n (%; 95% CI) 20 (63; 45.7-79.3) CR, n (%) 3 (9) PR, n (%) 17 (53) SD ≥ 16 weeks, n (%) 6 (19) Clinical benefit (CR + PR + SD ≥ 16 weeks), n (%) 26 (81) Median response duration: 17.8 months (95% CI, 15.9-37.0) Median PFS: 16.6 months (95% CI, 7.5-26.5) Thirty-two patients treated Seventeen treated solely on original regimen Three switched from original to revised regimen Twelve treated only on revised regimen Response duration was calculated among the 20 patients who exhibited a response. CI, confidence interval; CR, complete response; HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; ORR, overall response rate; PR, partial response; SD, stable disease. Conlin AK et al. Clin Breast Cancer. 2010;10(4):281-287.

Conclusioni NAB-paclitaxel viene impiegato oggi con schedula trisettimanale (260 mg/m2), ma le evidenze attualmente disponibili giustificano il suo impiego anche in somministrazione settimanale (150, 125, 100 mg/m2 ) La scelta della schedula deve essere guidata dalle terapie precedenti per la malattia metastatica, dalle condizioni generali della paziente e dall’eventuale combinazione con altri farmaci (chemioterapici e/o biologici)* I dati clinici supportano il trattamento con NAB-paclitaxel in MBC dalla 1° linea in poi, anche per le pz pre-trattate con taxani in adiuvante, ricadute o refrattarie La neuropatia sensoriale, che si manifesta in genere tardivamente nel corso del trattamento con NAB-paclitaxel, può essere gestita con riduzione/interruzione di dose e migliora rapidamente * Le linee-guida tedesche dell’AGO (Working Group on Breast Cancer) raccomandano la CT con singolo agente se il paziente progredisce lentamente e non soffre di sintomi considerevoli e di metastasi acute che ne minacciano la sopravvivenza