San Antonio Summary

[Joe]

After a long search, our organization has finally located an oncologist to interpret news releases. Here is what they felt were the highlights of December's San Antonio Meeting.

Regards
Joe



Highlights from San Antonio Breast Conference 2009

(1) Trastuzumab in Combination with Lapatinib is better than Lapatinib alone for metastatic disease
Kimberly Blackwell, MD, from Duke University, presented data that women with metastatic breast cancer who received trastuzumab in combination with lapatinib had an improvement in overall survival compared to those who received lapatinib alone. This study (EGF104900) randomized 296 patients with metastatic HER2-positive breast cancer to either lapatinib or lapatinib in combination with weekly trastuzumab. Approximately 30% of patients had received 6 or more prior chemotherapy regimens, and had received a median of 3 prior trastuzumab regimens for metastatic disease. The overall response rate was 6.9% in the lapatinib alone arm compared to 10.3% in the combination arm, with a 2.9 month improvement in median overall survival (9.5 vs 14.0 months). This survival advantage was seen even in the setting of 52% of patients in the single agent lapatinib arm undergoing a planned cross over to the combination arm at the time of progression. There was also no increase in cardiac toxicity in the combination. This results in particularly impressive since the majority of patients had progressed on several trastuzumab-based regimens.

(2) Trastuzumab-DM1 (T-DM1) in patients with HER2-metastatic breast cancer
Ian Krop, MD, PhD, from Dana-Farber Cancer Institute, presented a phase II study of T-DM1 for women with metastatic HER2-positive breast cancer. T-DM1 is a novel anti-HER2 antibody drug conjugate in development for the treatment of metastatic HER2-positive breast cancer. This agent combines the targeting properties of trastuzumab to the HER2-receptor along with the delivery of a chemotherapy agent, DM1. This study was a multi-institutional single-arm phase II study of 100 patients who had received prior anthracycline, taxane, capecitabine, lapatinib, and trastuzumab, with at least two prior HER2-directed regimens in the metastatic setting. Patients received T-DM1 at 3.6 mg/kg IV every 3 weeks. There was a 32.7% objective response rate found. This is particularly impressive in a population with a median time from metastatic diagnosis of over 3 years and over 2 years of prior HER2-directed therapy. T-DM1 was well-tolerated with no evidence of dose-limiting cardiotoxicity. It is anticipated that Genentech/Roche will seek accelerated approval for T-DM1, however it is unclear if approval will be made prior to the results of ongoing phase III studies. One phase III study with T-DM1 that is open is the EMILIA study. This study is compares T-DM1 to capecitabine+lapatinib for second-line therapy of HER2-positive metastatic breast cancer.

(3) Updated results from BCIRG 006: Slight advantage for adjuvant anthracycline-based regimen compared to the taxane-based treatment
Dennis Slamon, MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, presented the third analysis of the BCIRG 006 study. This trial compares chemotherapy alone (adriamycin+ cytoxan, followed by taxotere, ACT) to chemotherapy with herceptin (ACTH), and to a non-anthracycline-based chemotherapy regimen (taxotere+carboplatin+herceptin, TCH). In more than 3000 women, at 5 years, there were 29 fewer events in the anythracycline-based group than in the taxane-based group. This resulted in a 3% difference in disease-free survival between the two groups. Dr. Slamon felt that the differences in efficacy were outweighed by the toxicities. There was an increased risk of congestive heart failure (CHF) in the anthracycline-based chemotherapy group compared to the taxane-based treatment group (21 vs 4 cases of CHF). There were also 8 total cases of treatment-related leukemias, 6 among patients in the ACT group, 1 in the ACTH group, and 1 in the TCH group. However, others would argue that many of the cases of CHF among the patients in the anthracycline-group were reversible, and that there was not a difference in the number of cases of leukemia between the ACTH and TCH arms. Overall, there appears to be a slight advantage in efficacy for anthracyline-based adjuvant therapy compared to the taxane-based treatment, however longer-term follow-up is still needed.

(4) Updated results from N9831: Sequential trastuzumab also lower risk of recurrence
Edith Perez, MD, chair of the North Central Cancer Treatment Group Breast Committee, presented updated results of the N9831 study. After a median follow-up of 5.5 years, disease-free survival (DFS) was 84.1% for concurrent chemotherapy and trasuzumab, 80.1% for chemotherapy with sequential trastuzumab and 71.9% for chemotherapy alone. While there was not a statistically significant difference in DFS between the concurrent vs sequential treatment, there is a trend towards superiority of the concurrent treatment arm. Prior results had suggested that there was no benefit for sequential chemotherapy followed by trastuzumab compared to chemotherapy alone, however, these updated results suggest a statistically significant benefit of the sequential treatment compared to chemotherapy alone (p=0.005) In terms of cardiac safety, there was a 3.3% incidence of CHF for concurrent therapy compared to 2.8% for sequential therapy. While the benefit of trastuzumab appears greatest when given concurrently with chemotherapy, there is still some benefit to sequential trastuzumab compared to chemotherapy alone.

(5) Heavy consumption of alcohol may increase breast cancer recurrence
Dr. Marilyn Kwan, PhD, from Kaiser Permanente in Oakland, California, examined the association between alcohol intake and cancer recurrence and mortality in the Life After Cancer Epidemiology (LACE) Study, a prospective cohort study of 1897 early-stage breast cancer patients. After 8 years of follow-up, there were 349 breast cancer recurrence (18%) and 332 deaths (17%), with 57% of deaths attributable to breast cancer. Among those who drank 3-4 drinks per week, or more, there was a 1.3-fold increased risk of breast cancer recurrence, and a 1.5-fold increased risk of death due to breast cancer. This increased risk of recurrence was more pronounced in postmenopausal patients and obese patients. Based on these findings, some have recommending limiting alcohol intake to less than 3 drinks per week, particularly for those who are postmenopausal and obese.