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“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.
Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.
“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.
She presented these results at the 2020 San Antonio Breast Cancer Symposium.
Comparing IBIS-II DCIS with prior results
“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.
Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”
In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.
The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.
“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
IBIS-II DCIS details and results
Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.
The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.
“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”
Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).
Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).
Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.
Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
Adverse events could be the deciding factor
“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.
During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.
“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.
She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.
Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.
“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”
The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.
SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.
“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.
Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.
“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.
She presented these results at the 2020 San Antonio Breast Cancer Symposium.
Comparing IBIS-II DCIS with prior results
“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.
Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”
In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.
The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.
“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
IBIS-II DCIS details and results
Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.
The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.
“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”
Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).
Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).
Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.
Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
Adverse events could be the deciding factor
“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.
During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.
“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.
She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.
Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.
“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”
The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.
SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.
“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.
Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.
“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.
She presented these results at the 2020 San Antonio Breast Cancer Symposium.
Comparing IBIS-II DCIS with prior results
“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.
However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.
Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”
In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.
The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.
“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
IBIS-II DCIS details and results
Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.
The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.
“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”
Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).
Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).
Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.
Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
Adverse events could be the deciding factor
“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.
During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.
“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.
She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.
Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.
“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”
The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.
SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.
FROM SABCS 2020