1. DOTT . MAURO MINELLI U. O. C. ONCOLOGIA MEDICA OSPEDALE S. EUGENIO – ROMA OSPEDALE S. EUGENIO CARCINOMA DELLA MAMMELLA PREVENZIONE E TERAPIA UN MODELLO IN CONTINUA EVOLUZIONE ROMA, 11 DICEMBRE 2010 AULA GRILLI
6. RIVOLUZIONE DEI CONCETTI NEGLI ULTIMI 30 ANNI DA TRATTAMENTO MASSIMO TOLLERABILE CONCEZIONE ANATOMICA MEDICINA TRADIZIONALE A TRATTAMENTO MINIMO EFFICACE CONCEZIONE BIOLOGICA MEDICINA BASATA SULL’EVIDENZA
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22. ORMONOTERAPIA RISULTATI DEGLI STUDI CON INIBITORI DELLE AROMATASI IN ADIUVANTE GLOBALE VANTAGGIO IN DFS E TDR ; OS MENO SIGNIFICATIVO; EMERGE UN TREND NEL BIG 1-98 ATAC BIG 1-98 UPFRONT BIG 1-98 SEQUENZA ABCSG8 ITA ARNO IES MA17 FU mediano (mesi) 100 76 71 72 64 30 55 54 HR DFS 0,85 0,88 1,05 0,85 0,35 0,66 (EFS) 0,76 0,57 HR TDR 0,84 0,85 1,22 NR 0,49 NR 0,83 0,61 HR CBC 0,60 NR NR NR NR 97 vs 96% a 3aa 0,56 NR HR OS 0,97 0,87 1,13 0,78 0,56 0,53 0,83 0,82
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37. Herceptin ® plus paclitaxel: efficacy (IHC 3+) Baselga J. Oncology 2001;61(Suppl. 2):14–21
38. Herceptin ® plus paclitaxel: 39% increase in survival (IHC 3+) Smith IE. Anticancer Drugs 2001;12:S3–10 1.0 0.8 0.6 0.4 0.2 0 Time (months) 0 5 10 15 20 25 30 35 40 45 50 17.9 24.8 Probability of survival 39% Herceptin ® + paclitaxel Paclitaxel
39. Herceptin ® plus docetaxel: efficacy 12-month cut-off Marty M, et al. J Clin Oncol in press.
40. Herceptin ® plus docetaxel: 38% increase in survival 1.0 0.8 0.6 0.4 0.2 0 Probability of survival 0 3 6 9 12 15 18 21 24 27 30 33 36 Time (months) Intent-to-treat population, 12-month cut-off Documented crossover = 48% p=0.0062 22.1 30.5 Herceptin ® + docetaxel Docetaxel alone Marty M, et al. J Clin Oncol in press. 38%
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42. Trastuzumab Following Adjuvant Chemotherapy in HER2-Positive Early Breast Cancer (HERA Trial): Disease-Free and Overall Survival after 2 Year Median Follow-Up The HERA Study Team Presented by Ian E. Smith
43. HERA trial design Surgery + (neo)adjuvant CT ± RT Centrally confirmed IHC 3+ or FISH+ and LVEF ≥ 55% 2 years trastuzumab 8 mg/kg 6 mg/kg 3 weekly schedule 1 year trastuzumab 8 mg/kg 6 mg/kg 3 weekly schedule Women with locally determined HER2-positive invasive early breast cancer CT, chemotherapy; RT, radiotherapy X Randomization Observation After ASCO 2005, option of switch to trastuzumab
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45. Disease-free survival (ITT) Median FU 2 yrs 1703 1 591 1434 1127 742 383 140 1698 1 535 1330 984 639 334 127 100 80 60 40 20 0 Patients(%) Months from randomisation 1 year trastuzumab Observation 0 No. at risk Events HR 95% CI p value 0.64 0.54, 0.76 <0.0001 3-year DFS 80.6 74.3 218 321 6.3% 1 2 36 1 8 6 24 30
46. Overall survival (ITT) 1703 1627 1498 1190 794 407 146 100 80 60 40 20 0 Patients(%) Months from randomisation Observation No. at risk 1698 1 608 1453 1097 711 366 139 1 year trastuzumab Events HR 95% CI p value 0.66 0.47, 0.91 0.0115 3-year OS 92.4 89.7 0 59 90 Median FU 2 yrs 2.7% 1 2 36 1 8 6 24 30
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50. TERAPIA ORALE Patients with ErbB2-positive locally advanced or metastatic breast cancer who progressed after prior anthracycline, taxane and trastuzumab (N=399) R A N D O M I Z A T I O N Capecitabine 2500 mg/m 2 /day po Days 1–14 q 3 wk Lapatinib 1250 mg po qd continuously + capecitabine 2000 mg/m 2 /day po Days 1–14 q 3 wk EGF100151 (Cameron 1 ) 1. Cameron D, et al. Breast Can Res Treat 2008; DOI 10.1007/s10549-007-9885-0; 23.
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53. … ecco come siamo messi per arrivare al traguardo … direi che c’è ancora molto da lavorare
Editor's Notes
To summarise the efficacy data, the combination of first-line Herceptin ® plus docetaxel improved overall response rate, time to disease progression and median overall survival with statistical significance compared with docetaxel alone. Additionally, duration of response more than doubled from 5.1 to 11.4 months when Herceptin ® was added to docetaxel.
Median overall survival increased from 22.1 months in the docetaxel-alone arm to 30.5 months (p=0.0062) in the combination arm. This is a statistically significant difference and means that patients in the Herceptin ® plus docetaxel arm survived on average 8.4 months longer than those in the docetaxel-alone arm. This difference is seen despite the fact that approximately 48% of patients in the docetaxel arm crossed over to receive Herceptin ® at disease progression, which reduces the difference in survival seen between the two arms.
This is a reminder of the design IDMC have not so far suggested that detailed results of the 2 year arm should be released although we know that as for the 1 year arm, there ar significantly less events than in the Observation arm Following the ASCO 2005 results a protocol amendment was made to allow patients in the Observation arm to switch to Trastuzumab, irrespective of how long they had been in the trial since randomisation
DFS analysis with a median FU of 2 yrs, analysed by ITT- Continues to show a highly significant benefit for trastuzumab with a HR of 0.64 and an absolute DFS gain of 6.3% at 3 yrs Note the y axis goes from 0 to 100
The Overall S by ITT, which showed only a non-significant trend last year, now shows- a highly significant OS benefit for trastuzumab with a HR of 0.66 and a p of 0.0115 The absolute 3yr gain is 2.7%
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