References:
1. Krop I, Johnston S, Mayer IA, et al. FERGI phase II study of PI3K inhibitor pictilisib (GDC-0941) plus fulvestrant vs fulvestrant plus placebo in patients with ER+, aromatase inhibitor-(AI)-resistant advanced or metastatic breast cancer–part 1 results. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S2-02.
2. Perez EA, Ballman KV, Anderson SK, et al. Stromal tumor-infiltrating lymphocytes(S-TILs): in the alliance N9831 trial S-TILs are associated with chemotherapy benefit but not associated with trastuzumab benefit. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S1-06.
3. von Minckwitz G, Reimer T, Potenberg J, et al. The phase III ICE study: Adjuvant ibandronate with or without capecitabine in elderly patients with moderate or high risk early breast cancer. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S3-04.
4. Chlebowski RT, Blackburn GL, et al. Final survival analysis from the randomized Women's Intervention Nutrition Study (WINS) evaluating dietary intervention as adjuvant breast cancer therapy. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S5-08.
5. Nanda R, Chow LQ, Dees EC, et al. A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S1-09.
6. Hurvitz, S.A. et al. “Phase 3, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: BOLERO-1” SABCS Abstract S6-01
7. Cuzick J, Sestak I, Cawthorn S, et al. 16 year long-term follow-up of the IBIS-I breast cancer prevention trial. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S3-07.
8. Francis PA, Regan MM, Fleming GF, et al. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S3-08.
Slide 1: Addition of PI3 Kinase Inhibitor in ER-Positive Breast Cancer Raises Many Questions-
The results of the FERGI trial showed that adding the PI3K inhibitor pictilisib to fulvestrant in women with postmenopausal estrogen receptor (ER)-positive, HER2-negative breast cancer improved progression-free survival (PFS) by a median of 1.5 months. The PFS was 6.6 months in the combination arm compared with 5.1 months in the fulvestrant-alone arm (hazard ratio, 0.74;
P
= .0959). In an exploratory subgroup analysis, the patients that benefited most from the combination therapy had both ER-positive and progesterone receptor (PR)-positive disease. The PFS was 7.4 months and 3.7 months in the combination and placebo arms, respectively (
P
= .002). Patients enrolled on the trial had postmenopausal, ER-positive, PR-positive advanced disease and had previously failed on an aromatase inhibitor.
Image source: Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts.
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Slide 2: HER2-Positive Patients With High TIL Levels May Do Well With Chemotherapy Alone-
Patients with early-stage HER2-positive breast cancer who had high levels of stromal tumor-infiltrating lymphocytes (Str-TILs) had good outcomes with chemotherapy alone and may not require the addition of trastuzumab. These are the results from the phase III randomized N9831 trial. Among the 489 women who received chemotherapy alone, those with high Str-TIL levels had an 80% decreased chance of disease recurrence after a 6.9-year median follow-up. A previous trial update showed that chemotherapy plus trastuzumab improved recurrence-free survival. The new results suggest that TILs may be a biomarker to identify patients who can bypass trastuzumab therapy.
Image source: Edith A. Perez, MD, Mayo Clinic Cancer Center, Jacksonville, Florida.
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Slide 3: Elderly Early Breast Cancer Patients Do Not Benefit From the Addition of Capecitabine-
Elderly patients with moderate- to high-risk early-stage breast cancer who are not eligible for chemotherapy due to toxicity did not benefit from the addition of capecitabine to the bisphosphonate ibandronate. These are the results of the phase III ICE trial, which enrolled 1,358 patients. After a 61-month follow-up, there was no difference in either overall or disease-free survival between the group that received capecitabine and the group that received only ibandronate. Disease-free survival after 5 years was 78.8% and 75% in the capecitabine and control groups, respectively. At 5 years, the overall survival rate was 90% and 88% in the capecitabine and control groups, respectively. Eight percent of patients discontinued capecitabine treatment due to adverse events.
Image source:
Gunter von Minckwitz, MD, University of Frankfurt, Germany; chairman of the German Breast Group.
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Slide 4: Lower Death Rate Among Early-Stage Hormone-Negative Breast Cancer Patients With
Reduced Dietary Fat Intake-
There is emerging evidence that obesity is associated with poorer outcomes for certain breast cancers. The Women’s Intervention Nutrition Study randomized 2,437 early-stage breast cancer patients 60:40 to an intervention group and a control group. The intervention group members met with a dietician for eight one-on-one visits. The study indicated that a reduction in dietary fat intake for 5 years did not improve survival in the overall population of women with breast cancer enrolled in the trial; however, those with estrogen receptor (ER)- and progesterone receptor (PR)-negative disease did see reductions in death rates. The women with ER- and PR-negative disease who were part of the intervention group saw a 54% improvement in overall survival.
Image source: Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center, Los Angeles, California.
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Slide 5: Immunotherapy Antibody Produces Response in Triple-Negative Breast Cancer-
Of the 27 advanced triple-negative breast cancer patients in the phase I Keynote-012 trial who could be evaluated, 18.5% had an overall response, including one complete response (3.7%) to pembrolizumab, an anti-programmed cell death 1 (PD-1) monoclonal antibody. The patient who had a complete response had one prior line of systemic therapy and two patients with partial responses had five or more prior lines of therapy. Three of the five responders remained on therapy for at least 48 weeks, and the other two patients who had discontinued treatment at the time of analysis received therapy for 40 weeks. All patients enrolled on the trial had tumors that expressed PD-L1. Pembrolizumab was administered every 2 weeks at a 10-mg/kg dose.
Image source: Rita Nanda, MD, University of Chicago, Chicago, Illinois.
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Slide 6: No Benefit From Addition of Everolimus to First-Line Paclitaxel and Trastuzumab-
According to the results of the BOLERO-1 trial, the addition of the mTOR inhibitor everolimus to paclitaxel plus trastuzumab as a first-line therapy in HER2-positive breast cancer did not improve progression-free survival (PFS) (14.95 months vs 14.49 months in the everolimus and control paclitaxel plus trastuzumab arms, respectively;
P
= .1166). However, in the subset of patients with hormone receptor–negative disease, the PFS was improved by 7 months, even though the prespecified statistical significance threshold was not crossed. There were more deaths from adverse events in the everolimus treatment arm compared with the control arm (3.6% vs 0%).
Image source: Sara A. Hurvitz, MD, Breast Oncology Program, University of California, Los Angeles.
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Slide 7: Lower Rates of Breast Cancer With 5 Years of Tamoxifen-
According to the results of the International Breast Cancer Intervention Study-I (IBIS-1), after a median follow-up of 16 years, women who received 5 years of preventive tamoxifen had a lower rate of breast cancer incidence compared with the women in the placebo arm. Tamoxifen resulted in a 29% reduction in breast cancer compared with placebo, and the rates of estrogen receptor (ER)-positive breast cancers were reduced by 35%. Tamoxifen had no effect on ER-negative breast cancers. The trial randomized 7,154 pre- and postmenopausal women to receive either a daily 20-mg dose of tamoxifen for 5 years or placebo. The women had a high risk of breast cancer mostly due to a family history and were all between the ages of 35 and 70.
Image source: Jack Cuzick, PhD, Wolfson Institute of Preventive Medicine, Queen Mary University of London.
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Slide 8: SOFT Trial Distinguishes ER-Positive Patients Who Benefit Most From Ovarian Suppression-
The subgroup of early-stage premenopausal estrogen receptor (ER)-positive breast cancer patients who received initial chemotherapy prior to the SOFT trial benefited from the addition of ovarian suppression to tamoxifen. However, a greater reduction in recurrence occurred in high-risk women, 35 years of age or younger, who did not reach menopause after receiving initial chemotherapy, and were then given ovarian suppression in combination with the aromatase inhibitor exemestane. One in three women recurred within 5 years on tamoxifen alone compared with one in six women on the exemestane plus ovarian suppression regimen. Older premenopausal women with lower-risk disease who had not received prior chemotherapy did well with tamoxifen alone.
Image source: Prudence Francis, MD, Peter MacCallum Cancer Centre, Melbourne, Australia.
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