As Breast Cancer Awareness Month continues, attention turns to the Annual Congress of the European Society for Medical Oncology and the breast cancer trials recently presented there.
Results from two recent trials establish that 1 year is the optimum duration of adjuvant therapy with trastuzumab in patients with HER2+ early breast cancer. In the PHARE trial, 3,382 patients with HER2+ early breast cancer who had received at least 4 cycles of adjuvant chemotherapy were randomized to either 6 or 12 months of trastuzumab. After mean follow-up of 47.2 months, the non-inferiority of the 6-month regimen could not be demonstrated.
The second trial was the much-anticipated international, multicenter HERA Trial. In this study, 5,102 patients with HER2+ early breast cancer were randomized to treatment with trastuzumab for 1 year or 2 years or to observation after they completed primary therapy. After a median follow-up of 8 years, the investigators presented a landmark efficacy analysis of patients treated with trastuzumab who were disease-free 1 year after randomization.
Comparing the patients treated for 2 years with those treated for 1 year showed that they were similar in disease-free survival (HR 0.99, 95% CI 0.85 to 1.14, P= 0.8588) and overall survival (HR 1.05, 95% CI 0.86 to 1.28, P=0.6333). Time to distant recurrence was also similar in the two groups. Although cardiac death or severe congestive heart failure occurred at similar rates in the two groups, patients treated for 2 years had a higher incidence of left ventricular dysfunction. Thus, 1 year of adjuvant trastuzumab therapy remains the standard of care for patients with HER2+ early breast cancer.
Patients with HER2+ metastatic breast cancer who have been treated with trastuzumab and a taxane may benefit from further treatment with T-DM1, a conjugate of trastuzumab and the microtubule inhibitor DM1, according to results from the EMILIA trial. A total of 978 patients were randomized to T-DM1 (3.6 mg/kg IV q3w) or capecitabine (1000 mg/m2 twice daily, days 1-14 q3w) plus lapatinib (1250 mg PO once daily on days 1-21). Median progression-free survival was significantly better in the T-DM1 group (9.6 months vs 6.4 months, HR 0.650 [95% CI 0.549 to 0.771], P <0.0001). T-DM1 was superior to capecitabine/lapatinib in 1-year overall survival (84.7% vs 77.0%), 2-year overall survival (65.4% vs 47.5%), objective response (43.6% vs 30.8%), median duration of response in patients with objective response (12.6 months vs 6.5 months), clinical benefit rate (58.2% vs 44.2%), and median time to treatment failure (7.9 months vs 5.8 months, HR 0.703, 95% CI 0.602 to 0.820).
Grade 3 or 4 adverse events occurred more often in the capecitabine/lapatinib group than in the T-DM1 group (57.0% vs 40.8%). The most commonly reported grade 3 or 4 events with T-DM1 were thrombocytopenia (12.9%) and elevated serum concentrations of aspartate aminotransferase (4.3%) and alanine aminotransferase (2.9%). Incidence rates of cardiac adverse events, including left ventricular dysfunction, were low and similar in both treatment groups.
Anthracyclines may have a role in the treatment of triple negative and HER2 positive breast cancer, according to a study conducted in China that randomized 102 patients with stage IIB or III breast cancer to 6 cycles of docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC group) or docetaxel 75 mg/m2, an anthracycline, and cyclophosphamide 500 mg/m2 (TAC group). Either epirubicin 60 mg/m2 or doxorubicin 50 mg/m2 was allowed as the anthracycline regimen. After surgery, the rate of pathological complete remission, defined as no residual cancer in the breast or axillary lymph node, was 6.8% in the TC group and 17.6% in the TAC group, a nonsignificant difference. However, after a mean follow-up of 20 months (range, 3-36 months), event-free survival was 80.4% in the TAC group and 60.0% in the TC group (adjusted HR 2.42 [95% CI, 1.11 to 5.30], P = 0.027). Disease-free survival was also significantly better in the TAC group (84.3% vs 64.4%, adjusted HR 2.85 [95% CI: 1.21 to 6.74], P = 0.017). High rates of grade 3 to 4 neutropenia and leukopenia were reported in the TAC group, but no patients died during treatment.
In the NeoALTTO trial, women with breast cancer who underwent treatment with paclitaxel plus lapatinib and trastuzumab before surgery had a higher rate of pathological complete response (pCR) than women treated with paclitaxel and one of those drugs; however, they were no more likely to receive breast-conserving surgery. Examination of trial data revealed that mastectomy was more frequent in women <50 years old, those treated in a developing country, and those with a tumor that was multicentric, >5 cm in size, or ER–. All 17 patients who had lobular cancer received mastectomy regardless of whether they achieved pCR. Among women who were considered for breast-conserving surgery, pCR did not influence whether they received it. Thus, when the choice of surgery was considered, tumor characteristics outweighed response to treatment and many women were denied breast-conserving surgery despite having achieved pCR.
The role of weight gain in recurrence of breast cancer was investigated in a study that recruited 520 patients with early breast cancer. Weight and body mass index (BMI) were assessed within 1 month after surgery and again 24 months after completion of treatment. After median follow-up of 13 years, breast cancer recurred in 194 patients. Weight gain after diagnosis was significantly associated with higher risk of recurrence: breast cancer recurred in 34% of patients whose BMI increased <2 kg/m2 and 52% of those whose BMI increased >2 kg/m2.
Readers, we want to hear from you!
- Which breast cancer trial results presented at ESMO 2012 do you consider to be most significant?
- Will these trial results influence how you manage patients with breast cancer?