Abstract S5-06: Epirubicin and cyclophosphamide (EC) followed by paclitaxel (T) versus fluorouracil, epirubicin and cyclophosphamide (FEC) followed by T, all given every 3 weeks or 2 weeks, in node-positive early breast cancer (BC) patients (pts). Final results of the gruppo Italiano mammella (GIM)-2 randomized phase III study

Abstract

Background. Using a 2 × 2 factorial design, we compared the efficacy of two different schedules of chemotherapy (CT), dose-dense (DD) every 2 weeks versus standard duration every 3 weeks and the role of Fluorouracil (F) in addition to EC, in the adjuvant treatment of node positive BC pts. Patients and Methods. Node positive early BC pts younger than 70 years were eligible and randomly assigned to one of the following treatment arms: ARM A (4 courses of EC [90/600 mg/m2, on day 1, q 21] followed by 4 courses of T [175 mg/m2 on day 1, q 21]); ARM B (4 courses of FEC [600/90/600 mg/m2, on day 1, q 21] followed by 4 courses of T [175 mg/m2 on day 1, q 21]); ARM C (4 courses of EC [90/600 mg/m2, on day 1, q 14] followed by 4 courses of T [175 mg/m2 on day 1, q 14]); ARM D (4 courses of FEC [600/90/600 mg/m2, on day 1, q 14] followed by 4 courses of T [175 mg/m2 on day 1, q 14]). Pts enrolled in the DD arms (ARM C and D) received subcutaneous pegfilgrastim (6 mg) 24 hours after CT. HER2-positive pts enrolled after April 2006 received trastuzumab for 1 year at the end of CT. The primary study endpoint was disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. All analyses were conducted according to the intention-to-treat principle. Results. From April 2003 to July 2006, 2091 pts were enrolled (545 in ARM A, 544 in ARM B, 502 in ARM C, 500 in ARM D). The planned number of CT cycles was completed in 89% of pts in the DD group and in 88.1% of pts in the standard duration group. Pts treated with DD CT (ARM C + ARM D) experienced more frequently anemia (all grades: 67.2% vs 49.5%, p < .0001; G3-G4: 0.2% vs 1.4%, p = .004) and bone pain (53.5% vs 39.2%, p < .0001). Neutropenia occurred more frequently in standard duration arms (ARM A + ARM B): 66.7% vs 28.0%, p = < .0001. At a median follow up of 7.0 years, multivariate analysis, showed that DD treatments (ARM C + ARM D vs ARM A + ARM B) improved the primary endpoint, DFS (hazard ratio [HR] = 0.78; 95% CI 0.66-0.94; p = .007), and OS (HR = 0.68; 95% CI 0.52-0.87; p = .002). Conversely, the addition of F to EC did not improve clinical outcomes: the HR for DFS and OS (ARM A + ARM C vs ARM B + ARM D) were respectively 0.98 (95% CI 0.83-1.17; p = .85) and 0.93 (95% CI 0.73-1.19; p = .578). Subgroup analyses revealed that the benefits associated with DD CT were independent of hormone receptor status: in hormone receptor positive the HRs for DFS and OS were 0.80 (0.65-0.98) and 0.69 (0.51-0.93) respectively; in hormone receptor negative the HRs for DFS and OS were 0.67 (0.47-0.95) and 0.57 (0.36-0.92) respectively (p for interaction for DFS: 0.339; p for interaction for OS: 0.495). Pathological tumor size, nodal status (1-3 vs ≥ 4 positive nodes), histological grade and hormone receptor status were independently associate with DFS and OS. Conclusions. DD CT as adjuvant treatment in node positive BC pts, improves DFS and OS significantly. Conversely, the addition of F to EC does not improve clinical outcomes. (ClinicalTrials.gov number, NCT00433420). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-06.

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2017

“…Based on data from the Italian Grupo Italiano Mamella (GIM) study presented by Cognetti et al [76] at the San Antonio Breast Cancer Symposium (SABCS) 2013, epi rubi cin/cyclophosphamide (EC) followed by paclitaxel is equally effective to EC plus 5fluorouracil (FEC) followed by pacli taxel. Therefore, our new guideline recommendation is EC without the addition of 5fluorouracil.…”

“…For dosedense regimens, additional knowledge has accu mulated in the year 2014: -The Italian GIM study presented by Cognetti et al [76] has shown that EC 90/600 q2w with pegfilgrastim followed by paclitaxel 175 q2w is superior to the same regimen applied at 3weekly intervals. -The NSABP B38 trial published by Swain et al [77] has shown that 6 cycles of TAC is equally effective to dose dense EC followed by paclitaxel q2w.…”

Adjuvante und neoadjuvante Chemotherapie des Mammakarzinoms

“…Insbesondere Patientinnen mit estrogenrezeptornegativen (ER-negativen) Tumoren scheinen zu profitieren. Die Wirksamkeit dieses Konzepts ist durch eine zweite Studie bestätigt worden [8]), bei der die Verdichtung der Therapie auf zweiwö-chentliche Zyklen ebenfalls mit einer signifikanten Effektivitätssteigerung im Vergleich zur dreiwöchentlichen Applikation verbunden war. Die Ergebnisse waren unabhängig vom Hormonrezeptorstatus.…”

Onkologie. Reflexionen nach dem 36. „San Antonio Breast Cancer Symposium“ – Was gibt es Neues?

“…Cognetti et al [9] gingen mit der GIM-II-Studie den Fragen nach, ob die dosisdichte Therapie (q2w) mittels 4-mal Epirubicin/ Cyclophosphamid gefolgt von 4-mal Paclitaxel der herkömmlichen Gabe (q3w) überlegen ist und ob die zusätzliche Gabe von Fluorouracil einen weiteren Vorteil beim nodal-positiven Mammakarzinom erbringt. Dabei zeigte sich ein hochsignifikanter Vorteil durch die dosisdichte Gabe sowohl für das krankheitsfreie Überleben (19%), als auch für das Gesamtüberleben (32%) der insgesamt 2091 Patientinnen.…”