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0172 Neoadjuvant gemcitabine plus doxorubicin (G+A) versus FAC regimen for locally advanced breast cancer patients (phase III randomized study)
Friday, 13 March 2009
Friday, 13 March 2009
Neoadjuvant (pre-operative) therapy 0170
Phase II trial of neoadjuvant sequential FEC100 followed by docetaxel, carboplatin and trastuzumab (TCH) for HER-2 over-expressing locally advanced breast cancer (LABC): A multi-centre study from British Columbia
S. Chia1 , C. Bryce1 , G. Pansegrau2 , N. Macpherson3 , S. Ellard4 , D. Jepson5 , C. Yu5 , S. Nuraney5 , A. Attwell3 , M. Hayes6 , H. Kennecke1 , K. Gelmon1 . 1 Medical Oncology, British Columbia Cancer Agency, Vancouver, 2 Medical Oncology, British Columbia Cancer Agency, Surrey, 3 Medical Oncology, British Columbia Cancer Agency, Victoria, 4 Medical Oncology, British Columbia Cancer Agency, Kelowna, 5 Clinical Trials Unit, 6 Pathology, British Columbia Cancer Agency, Vancouver, Canada Goals: There have been recent phase II and III trials demonstrating improved pathological complete responses (pCR) in HER-2 positive breast cancer treated with neoadjuvant trastuzumab concurrent with chemotherapy. The number of patients on these trials however is significantly fewer, and many of these trials are a mixture of primary operable and LABC. We have completed a multi-centre phase II trial of neoadjuvant chemotherapy and trastuzumab in a HER-2 positive LABC population. Methods: Women with HER-2 positive (IHC 3+ or FISH+) stage IIB–IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500 mg/m2 ) followed by 4 cycles of TCH (Docetaxel 75 mg/m2 , carboplatin AUC 6, trastuzumab 8 mg/kg loading then 6 mg/kg q3 weekly). Trastuzumab was also continued adjuvantly for 9 months. Cardiac monitoring every 3 months was mandated. A correlative translational component with baseline and interval biopsies and serum collection was also performed. Results: A total of 30 patients (3 stage IIB; 14 IIIA; 10 IIIB and 3 IIIC) in 4 centres were accrued. Median age was 49 years (26−77 years). 60% of tumours were ER negative. There were 6 episodes (20%) of febrile neutropenia. Mean baseline LVEF was 64.6%. Mean LVEF at month 12 was 58.7% for an absolute mean difference of 5.9% (0−20%). There was one clinical CHF and 2 asymptomatic falls in LVEF 20% with an absolute LVEF < 50%. Seven patients underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 60% (18/30). The 2 year DFS and OS is 87% and 93% respectively. Conclusion: This multi-centre phase II trial clearly demonstrates significant activity for neoadjuvant anthracyclines followed by concurrent taxane, platinum and trastuzumab in a HER-2 positive LABC population. Overall the treatment regimen was relatively well tolerated aside for a higher than expected rate of febrile neutropenia.
Poster Session II. Neoadjuvant (pre-operative) therapy
(MRD) as isolated residual cancer cells (i+) or pT1mic. Linear correlation has been performed applying Bravais–Pearson test (negative result, r = 0). Results: We enrolled 31 pts; all valuable for response. Characteristics: median age: 42 yrs (25−64); pre-menopausal: 19 pts; 17, 11 and 2 out of 31 pts were respectively G3, G2 and G1; 17 out of 31 were ER/PgR+ve; median p53 and Ki67/MIB1 were respectively 7% (12−80) and 36% (4−70); 12, 11, and 8 out of 31 pts were respectively HER2−ve, HER2 2+ and HER2 3+ on ICH evaluation. We observed 13 cCR, 16 cPR and 2 cSD. Pathologic responses were: 6 complete and 5 MRD. We found a negative correlation between response and ER/PgR status, a positive one between response and histological grading, any correlation between response and p53, Ki67 and HER2. Conclusion: Our data confirm that TAC is a highly effective regimen as primary therapy of LABC especially for ER/PgR−ve and G3 tumors. Immunohistochemical cytokeratine assays (CK 5/14, 8/18) are ongoing and its correlations with response will be presented.
0172
Neoadjuvant TAC for locally advanced breast cancer: Correlation between response and biological features
G.P. Giardina1 , I. Marcon1 , I. Vallini1 , G. Pinotti1 , C. Capella2 , A. Chiaravalli2 . 1 Medical Oncology, 2 Patology Unit, Ospedale di Circolo e Fondazione Macchi, Varese, Italy Goals: Primary Chemotherapy has an established role in Locally Advanced Breast Cancer (LABC) and several studies have shown a strong correlation between pathologic complete response (pCR) and survival; and it is demonstrated that pCR is significantly less frequent in ER+ve tumours than in ER−ve ones. Our previous reports have shown that TAC regimen is highly effective in neoadjuvant setting with an 86% of overall response rate. The aim of this study was to correlate response and biological features of the tumour. Methods: A series of consecutive chemotherapy-naive patients (pts) with LABC (stage T 2/3, N 0/2, M0) were treated with 4/6 cycles of TAC (Docetaxel 75 mg/m2 , Doxorubicin 50 mg/m2 , Cyclophosphamide 500 mg/m2 , day 1 q21) plus ovarian function suppression in ER+ve premenopausal pts. All pts underwent core-biopsies before primary therapy with a complete histo-biological evaluation of the tumour. pCR was defined as absence of invasive cancer or presence of DCIS only and minimal residual disease
Neoadjuvant gemcitabine plus doxorubicin (G+A) versus FAC regimen for locally advanced breast cancer patients (phase III randomized study)
H.M. El-Zawahry1 , R.M. Gaffar1 , H.M. Abdel Raouf2 , E.A. Fikary1 , H.M. Ramadan1 , H.A. Ezzat1 . 1 Medical Oncology, 2 Pathology, National Cancer Institute, Cairo, Egypt Goals: To evaluate the clinical response and pathological response after neoadjuvant chemotherapy with gemcitabine plus doxorubicin (G+A) versus doxorubicin, fluorouracil, and cyclophosphamide (FAC) in locally advanced breast cancer. Methods: This randomized, uni center study conducted in previously untreated women with breast ca. who were not accessible for breastconservative surgery. Pretreatment characteristics of the 60 randomly assigned patients were well balanced between treatment groups. Approximately three fourths of patients had adenocarcinoma, two thirds of patients presented with T2 tumors, and 65% had estrogen or progesterone receptor-positive disease. Patients in both group received all three Neoadjuvant courses of planned chemotherapy. Surgery was performed in 28 patients (93%) in the G+A arm and in 26 patients (87%) in the FAC arm. Results: After 3 cycles of neoadjuvant breast preservation was feasible in 64%of G+A arm. There was no histologic evidence of invasive disease in 25% and 12% of patients after three courses of G+A and FAC, respectively. Pathological CR in the G+A and FAC treatment arms was 23% and 9%, respectively. Conclusion: gemcitabine with doxorubicin is a promising neoadjuvant regimen for patients with breast cancer (T2 or T3) not amenable to conservative surgery and relates favourably to a standard FAC anthracycline regimen.
0173 0171
S61
Predictive value of 18F-FDG PET−CT in primary breast cancer patients receiving neoadjuvant chemotherapy
J.W.H. Tsang1 , D. Yeung2 , A.C.Y. Chan3 , C.H.N. Wong3 , L.W.S. Leung3 , C.S.Y. Lo3 , L.H.K. Fung3 , R.J. Epstein4 , A. Kwong3 . 1 Department of Clinical Oncology and Department of Medicine, 2 Department of Diagnostic Radiology, 3 Department of Surgery, 4 Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region of China Goals: Neoadjuvant chemotherapy has become a standard for treatment of locally advanced breast cancer to reduce tumour bulk, control occult disease and provide insight in tumour response. 18FDG PET-CT has become popular to assess chemotherapy response of primary breast cancer, but the predictive value of PET-CT is not well studied. We aim to examine the predictive value of PET-CT in the neoadjuvant setting of primary breast cancer. Methods: We conducted a retrospective study of 57 Hong Kong Chinese locally advanced breast cancer patients treated with neoadjuvant chemotherapy at the University of Hong Kong during April 2004 and September 2006. Tumour features, clinical response by tumour size, radiological response with mammography, ultrasonography, PET-CT and pathological response of the subjects were assessed.
Friday, 13 March 2009
Neoadjuvant (pre-operative) therapy 0170
Phase II trial of neoadjuvant sequential FEC100 followed by docetaxel, carboplatin and trastuzumab (TCH) for HER-2 over-expressing locally advanced breast cancer (LABC): A multi-centre study from British Columbia
S. Chia1 , C. Bryce1 , G. Pansegrau2 , N. Macpherson3 , S. Ellard4 , D. Jepson5 , C. Yu5 , S. Nuraney5 , A. Attwell3 , M. Hayes6 , H. Kennecke1 , K. Gelmon1 . 1 Medical Oncology, British Columbia Cancer Agency, Vancouver, 2 Medical Oncology, British Columbia Cancer Agency, Surrey, 3 Medical Oncology, British Columbia Cancer Agency, Victoria, 4 Medical Oncology, British Columbia Cancer Agency, Kelowna, 5 Clinical Trials Unit, 6 Pathology, British Columbia Cancer Agency, Vancouver, Canada Goals: There have been recent phase II and III trials demonstrating improved pathological complete responses (pCR) in HER-2 positive breast cancer treated with neoadjuvant trastuzumab concurrent with chemotherapy. The number of patients on these trials however is significantly fewer, and many of these trials are a mixture of primary operable and LABC. We have completed a multi-centre phase II trial of neoadjuvant chemotherapy and trastuzumab in a HER-2 positive LABC population. Methods: Women with HER-2 positive (IHC 3+ or FISH+) stage IIB–IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500 mg/m2 ) followed by 4 cycles of TCH (Docetaxel 75 mg/m2 , carboplatin AUC 6, trastuzumab 8 mg/kg loading then 6 mg/kg q3 weekly). Trastuzumab was also continued adjuvantly for 9 months. Cardiac monitoring every 3 months was mandated. A correlative translational component with baseline and interval biopsies and serum collection was also performed. Results: A total of 30 patients (3 stage IIB; 14 IIIA; 10 IIIB and 3 IIIC) in 4 centres were accrued. Median age was 49 years (26−77 years). 60% of tumours were ER negative. There were 6 episodes (20%) of febrile neutropenia. Mean baseline LVEF was 64.6%. Mean LVEF at month 12 was 58.7% for an absolute mean difference of 5.9% (0−20%). There was one clinical CHF and 2 asymptomatic falls in LVEF 20% with an absolute LVEF < 50%. Seven patients underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 60% (18/30). The 2 year DFS and OS is 87% and 93% respectively. Conclusion: This multi-centre phase II trial clearly demonstrates significant activity for neoadjuvant anthracyclines followed by concurrent taxane, platinum and trastuzumab in a HER-2 positive LABC population. Overall the treatment regimen was relatively well tolerated aside for a higher than expected rate of febrile neutropenia.
Poster Session II. Neoadjuvant (pre-operative) therapy
(MRD) as isolated residual cancer cells (i+) or pT1mic. Linear correlation has been performed applying Bravais–Pearson test (negative result, r = 0). Results: We enrolled 31 pts; all valuable for response. Characteristics: median age: 42 yrs (25−64); pre-menopausal: 19 pts; 17, 11 and 2 out of 31 pts were respectively G3, G2 and G1; 17 out of 31 were ER/PgR+ve; median p53 and Ki67/MIB1 were respectively 7% (12−80) and 36% (4−70); 12, 11, and 8 out of 31 pts were respectively HER2−ve, HER2 2+ and HER2 3+ on ICH evaluation. We observed 13 cCR, 16 cPR and 2 cSD. Pathologic responses were: 6 complete and 5 MRD. We found a negative correlation between response and ER/PgR status, a positive one between response and histological grading, any correlation between response and p53, Ki67 and HER2. Conclusion: Our data confirm that TAC is a highly effective regimen as primary therapy of LABC especially for ER/PgR−ve and G3 tumors. Immunohistochemical cytokeratine assays (CK 5/14, 8/18) are ongoing and its correlations with response will be presented.
0172
Neoadjuvant TAC for locally advanced breast cancer: Correlation between response and biological features
G.P. Giardina1 , I. Marcon1 , I. Vallini1 , G. Pinotti1 , C. Capella2 , A. Chiaravalli2 . 1 Medical Oncology, 2 Patology Unit, Ospedale di Circolo e Fondazione Macchi, Varese, Italy Goals: Primary Chemotherapy has an established role in Locally Advanced Breast Cancer (LABC) and several studies have shown a strong correlation between pathologic complete response (pCR) and survival; and it is demonstrated that pCR is significantly less frequent in ER+ve tumours than in ER−ve ones. Our previous reports have shown that TAC regimen is highly effective in neoadjuvant setting with an 86% of overall response rate. The aim of this study was to correlate response and biological features of the tumour. Methods: A series of consecutive chemotherapy-naive patients (pts) with LABC (stage T 2/3, N 0/2, M0) were treated with 4/6 cycles of TAC (Docetaxel 75 mg/m2 , Doxorubicin 50 mg/m2 , Cyclophosphamide 500 mg/m2 , day 1 q21) plus ovarian function suppression in ER+ve premenopausal pts. All pts underwent core-biopsies before primary therapy with a complete histo-biological evaluation of the tumour. pCR was defined as absence of invasive cancer or presence of DCIS only and minimal residual disease
Neoadjuvant gemcitabine plus doxorubicin (G+A) versus FAC regimen for locally advanced breast cancer patients (phase III randomized study)
H.M. El-Zawahry1 , R.M. Gaffar1 , H.M. Abdel Raouf2 , E.A. Fikary1 , H.M. Ramadan1 , H.A. Ezzat1 . 1 Medical Oncology, 2 Pathology, National Cancer Institute, Cairo, Egypt Goals: To evaluate the clinical response and pathological response after neoadjuvant chemotherapy with gemcitabine plus doxorubicin (G+A) versus doxorubicin, fluorouracil, and cyclophosphamide (FAC) in locally advanced breast cancer. Methods: This randomized, uni center study conducted in previously untreated women with breast ca. who were not accessible for breastconservative surgery. Pretreatment characteristics of the 60 randomly assigned patients were well balanced between treatment groups. Approximately three fourths of patients had adenocarcinoma, two thirds of patients presented with T2 tumors, and 65% had estrogen or progesterone receptor-positive disease. Patients in both group received all three Neoadjuvant courses of planned chemotherapy. Surgery was performed in 28 patients (93%) in the G+A arm and in 26 patients (87%) in the FAC arm. Results: After 3 cycles of neoadjuvant breast preservation was feasible in 64%of G+A arm. There was no histologic evidence of invasive disease in 25% and 12% of patients after three courses of G+A and FAC, respectively. Pathological CR in the G+A and FAC treatment arms was 23% and 9%, respectively. Conclusion: gemcitabine with doxorubicin is a promising neoadjuvant regimen for patients with breast cancer (T2 or T3) not amenable to conservative surgery and relates favourably to a standard FAC anthracycline regimen.
0173 0171
S61
Predictive value of 18F-FDG PET−CT in primary breast cancer patients receiving neoadjuvant chemotherapy
J.W.H. Tsang1 , D. Yeung2 , A.C.Y. Chan3 , C.H.N. Wong3 , L.W.S. Leung3 , C.S.Y. Lo3 , L.H.K. Fung3 , R.J. Epstein4 , A. Kwong3 . 1 Department of Clinical Oncology and Department of Medicine, 2 Department of Diagnostic Radiology, 3 Department of Surgery, 4 Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region of China Goals: Neoadjuvant chemotherapy has become a standard for treatment of locally advanced breast cancer to reduce tumour bulk, control occult disease and provide insight in tumour response. 18FDG PET-CT has become popular to assess chemotherapy response of primary breast cancer, but the predictive value of PET-CT is not well studied. We aim to examine the predictive value of PET-CT in the neoadjuvant setting of primary breast cancer. Methods: We conducted a retrospective study of 57 Hong Kong Chinese locally advanced breast cancer patients treated with neoadjuvant chemotherapy at the University of Hong Kong during April 2004 and September 2006. Tumour features, clinical response by tumour size, radiological response with mammography, ultrasonography, PET-CT and pathological response of the subjects were assessed.