Background: The combination of anthracyclines and anti-HER-2 agents is highly active in HER-2 positive breast cancer, but its use is limited by an enhanced risk of cardiac toxicity. We are running a randomized phase II trial of combined preoperative chemotherapy (CT) with anthracycline plus trastuzumab, lapatinib, or both in HER-2 positive stage II-IIIA breast cancer patients. Aims of the study are the percentage of pathological complete response (pCR = breast + axillary nodes) and cardiac safety. We report the updated cardiac safety and activity data following the IDMC recommendation to continue study accrual. Methods: CT consists of sequential paclitaxel (P) 80 mg/m2 weekly for 12 weeks followed by 4 courses of FE75C administered every 3 weeks. Arm A is CT + trastuzumab 2 mg/kg weekly; arm B is CT + lapatinib 1500 mg po daily; arm C is CT + trastuzumab 2 mg/kg weekly + lapatinib 1,000 mg po daily. Both trastuzumab and lapatinib are started concomitantly with the first P administration, and are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FE75C, and at the completion of treatment. The planned sample size is 120 patients, and has been calculated according to the two steps Simon's design. Results: 53 out of the 120 planned patients have been randomized: 16 in arm A, 17 in arm B, and 20 in arm C. Median age is 48 years (range 27-66). The mean LVEF was 63% (range 54-77%) at baseline, 61% (50-78%) at the completion of weekly P + trastuzumab, lapatinib, or trastuzumab + lapatinib, and 60.3% (54-74%) at the completion of the whole treatment plan. Thirty patients underwent surgery: 19 patients (63%) received breast conserving surgery; 13 patients (43%) achieved a pCR. Conclusions Following the updated interim analysis, the combination of T, L or both with an anthracycline-containing regimen is feasible, with very interesting level of activity. The next planned analysis will be performed when 60 patients will be evaluable and will be presented at the Meeting.

Anthracycline-based preoperative chemotherapy plus lapatinib and trastuzumab or both in HER2-positive breast cancer: Preliminary cardiac safety report of the CHER LOB trial / Guarneri, Valentina; A., Frassoldati; A., Bottini; K., Cagossi; L., Cavanna; A., Ravaioli; D., Amadori; G., Giardina; C., Oliva; Conte, Pierfranco. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - vol 27, No 15s (abstract 573):(2009), pp. 24s-24s. ((Intervento presentato al convegno 2009 American Society of Clinical Oncology Annual Meeting tenutosi a Orlando, FL nel May 29-June2, 2009.

Anthracycline-based preoperative chemotherapy plus lapatinib and trastuzumab or both in HER2-positive breast cancer: Preliminary cardiac safety report of the CHER LOB trial.

GUARNERI, Valentina;CONTE, Pierfranco
2009

Abstract

Background: The combination of anthracyclines and anti-HER-2 agents is highly active in HER-2 positive breast cancer, but its use is limited by an enhanced risk of cardiac toxicity. We are running a randomized phase II trial of combined preoperative chemotherapy (CT) with anthracycline plus trastuzumab, lapatinib, or both in HER-2 positive stage II-IIIA breast cancer patients. Aims of the study are the percentage of pathological complete response (pCR = breast + axillary nodes) and cardiac safety. We report the updated cardiac safety and activity data following the IDMC recommendation to continue study accrual. Methods: CT consists of sequential paclitaxel (P) 80 mg/m2 weekly for 12 weeks followed by 4 courses of FE75C administered every 3 weeks. Arm A is CT + trastuzumab 2 mg/kg weekly; arm B is CT + lapatinib 1500 mg po daily; arm C is CT + trastuzumab 2 mg/kg weekly + lapatinib 1,000 mg po daily. Both trastuzumab and lapatinib are started concomitantly with the first P administration, and are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FE75C, and at the completion of treatment. The planned sample size is 120 patients, and has been calculated according to the two steps Simon's design. Results: 53 out of the 120 planned patients have been randomized: 16 in arm A, 17 in arm B, and 20 in arm C. Median age is 48 years (range 27-66). The mean LVEF was 63% (range 54-77%) at baseline, 61% (50-78%) at the completion of weekly P + trastuzumab, lapatinib, or trastuzumab + lapatinib, and 60.3% (54-74%) at the completion of the whole treatment plan. Thirty patients underwent surgery: 19 patients (63%) received breast conserving surgery; 13 patients (43%) achieved a pCR. Conclusions Following the updated interim analysis, the combination of T, L or both with an anthracycline-containing regimen is feasible, with very interesting level of activity. The next planned analysis will be performed when 60 patients will be evaluable and will be presented at the Meeting.
vol 27, No 15s (abstract 573)
24s
24s
Guarneri, Valentina; A., Frassoldati; A., Bottini; K., Cagossi; L., Cavanna; A., Ravaioli; D., Amadori; G., Giardina; C., Oliva; Conte, Pierfranco
Anthracycline-based preoperative chemotherapy plus lapatinib and trastuzumab or both in HER2-positive breast cancer: Preliminary cardiac safety report of the CHER LOB trial / Guarneri, Valentina; A., Frassoldati; A., Bottini; K., Cagossi; L., Cavanna; A., Ravaioli; D., Amadori; G., Giardina; C., Oliva; Conte, Pierfranco. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - vol 27, No 15s (abstract 573):(2009), pp. 24s-24s. ((Intervento presentato al convegno 2009 American Society of Clinical Oncology Annual Meeting tenutosi a Orlando, FL nel May 29-June2, 2009.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/814735
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact