Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer ...does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.
In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18–70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0–1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) on day 1 every 3 weeks, followed by four cycles of intravenous paclitaxel (175 mg/m2) on day 1 every 3 weeks (q3EC-P group); four cycles of intravenous FEC (fluorouracil 600 mg/m2, epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2) on day 1 every 3 weeks, followed by four cycles of intravenous paclitaxel (175 mg/m2) on day 1 every 3 weeks (q3FEC-P group); dose-dense EC-P regimen, with the same doses and drugs as the q3EC-P group but administered every 2 weeks (q2EC-P group); and the dose-dense FEC-P regimen, with the same doses and drugs as the q3FEC-P group but given every 2 weeks (q2FEC-P). Randomisation, with stratification by centre, with permuted blocks of size 12, was done with a centralised, interactive, internet-based system that randomly generated the treatment allocation. The primary endpoint was disease-free survival in the intention-to-treat population, comparing different chemotherapy schedule (dose-dense vs standard-dose intervals) and regimen (FEC-P vs EC-P). Safety population included all patients that received at least one dose of any study drug according to the treatment received. This trial is registered with ClinicalTrials.gov, NCT00433420, and is now closed.
Between April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4–16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years 95% CI 15·51–not reached vs not reached 17·54–not reached; unadjusted hazard ratio 1·12 95% CI 0·98–1·29; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached 95% CI 17·45–not reached vs 16·52 14·24–17·54; 0·77 95% CI 0·67–0·89; p=0·0004). The most common grade 3–4 adverse events were neutropenia (200 37% of 536 patients in the q3EC-P group vs 257 48% of 533 in the q3FEC-P group vs 50 10% of 496 q2EC-P vs 97 20% of 492) and alopecia (238 44% vs 249 47% vs 228 46% vs 235 48%). During extended follow-up, no further grade 3–4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.
Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.
Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still ...represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.
Abstract Adjuvant trastuzumab (AT) dramatically improved HER2-positive breast cancer prognosis. Relapsed disease after AT has different patterns and information is available from observational ...studies. In this Review Chemotherapy regimens combined to anti-HER2 blockade are discussed, focusing in particular the role of anthracyclines, taxanes and capecitabine. The use of trastuzumab beyond progression and the role of other anti-HER2 agents like lapatinib, pertuzumab and T-DM1 are explored, as also dual blockade and in trastuzumab resistant Patients. Metastatic “de novo” HER2 Luminal (co-expression of HER2 and hormone receptors) Patients are eligible for anastrozole and trastuzumab but if pretreated with trastuzumab they are also eligible for lapatinib and letrozole. In any case endocrine treatment plays a complementary role to chemotherapy which remains pivotal. The last topic explored is treatment options for patients with brain metastases where both trastuzumab given concurrent with radiotherapy or lapatinib and capecitabine appear as potentially active.
Background: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. Patients and methods: ...Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. Results: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. Conclusions: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.
Mustacchi G, De Laurentiis MMustacchi G, De Laurentiis M. Drug Des Devel Ther. 2015;9:4303-4318.On page 4315, Disclosure section, "This work was supported by an unconditional grant from Editree ...editors, Italy, and both authors received a fee. Giorgio Mustacchi receives honoraria from Roche, Celgene, and EISAI. Michelino De Laurentiis receives honoraria from Roche, Celgene, EISAI, Novartis, and AstraZeneca. The authors report no other conflicts of interest in this work." should have read "The authors report no conflict of interest with this work".Read the original article
Breast cancer (BC) is the most frequent tumor worldwide. Triple-negative BCs are characterized by the negative estrogen and progesterone receptors and negative HER2, and represent 15% of all BCs. In ...this review, data on the use of taxanes in triple-negative BCs are analyzed, concluding they are effective in any clinical setting (neoadjuvant, adjuvant, and metastatic). Further, the role of nab-paclitaxel (formulation of albumin-bound paclitaxel) in these tumors is also evaluated. The available data show the clinical potential of nab-paclitaxel based combinations in terms of long-duration response, increased survival, and better quality of life of patients with triple-negative metastatic BC. The ongoing trials will give further information on the better management of this type of tumor.
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