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Boost dose reduces recurrence in high-risk DCIS
Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.
Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.
Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.
The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:
- WBI at 50 Gy in 25 fractions
- WBI at 42.5 Gy in 16 fractions
- WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
- WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.
In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.
All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
Giving a boost to better outcomes
The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.
There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).
The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).
The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).
There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).
Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
Reduce the boost dose?
A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.
“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.
“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.
Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.
Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.
The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.
Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.
Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.
Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.
The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:
- WBI at 50 Gy in 25 fractions
- WBI at 42.5 Gy in 16 fractions
- WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
- WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.
In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.
All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
Giving a boost to better outcomes
The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.
There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).
The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).
The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).
There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).
Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
Reduce the boost dose?
A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.
“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.
“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.
Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.
Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.
The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.
Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.
Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.
Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.
The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:
- WBI at 50 Gy in 25 fractions
- WBI at 42.5 Gy in 16 fractions
- WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
- WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.
In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.
All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
Giving a boost to better outcomes
The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.
There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).
The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).
The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).
There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).
Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
Reduce the boost dose?
A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.
“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.
“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.
Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.
Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.
The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.
FROM SABCS 2020
U.S. cancer death rates drop for second year in a row
The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.
“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.
“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.
Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.
The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.
On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.
“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
New cancer cases
The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.
The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.
As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.
Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.
“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.
In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
Increase in incidence at common sites
Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.
For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence.
“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.
Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.
“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.
On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.
Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.
Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.
And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.
“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.
“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.
Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.
The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.
On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.
“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
New cancer cases
The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.
The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.
As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.
Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.
“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.
In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
Increase in incidence at common sites
Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.
For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence.
“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.
Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.
“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.
On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.
Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.
Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.
And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.
“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.
“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.
Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.
The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.
On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.
“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
New cancer cases
The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.
The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.
As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.
Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.
“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.
In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
Increase in incidence at common sites
Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.
For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence.
“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.
Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.
“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.
On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.
Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.
Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.
And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.
The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
RSClin: A new tool for ‘TAILOR-ing’ treatment in early breast cancer
When results of the TAILORx trial were presented at ASCO 2018, many oncologists thought it seemed too simple that a single number from a genomic assay could separate patients who would and would not benefit from adjuvant postoperative chemotherapy.
Those oncologists were right to be skeptical. Subsequent data indicated that better predictive tools were needed.
A new tool called “RSClin” may fit the bill. RSClin integrates the prognostic and predictive value of the 21-gene Oncotype DX recurrence score (RS) with the additional prognostic information conveyed by patient age, tumor grade, and tumor size.
RSClin provides individualized estimates of distant relapse risk for women with node-negative, endocrine sensitive, HER2/neu oncogene-negative early breast cancer – and a quantification of the additive freedom from distant relapse if that patient receives adjuvant chemotherapy. The tool is now available via a tab on the professional portal at https://online.genomichealth.com/.
Details on RSClin, including how the tool was developed and validated, were presented at the 2020 San Antonio Breast Cancer Symposium by Joseph A. Sparano, MD, of Albert Einstein College of Medicine in New York.
Beyond the initial publication of TAILORx
Results from the TAILORx trial published in The New England Journal of Medicine in 2018 offered the potential for genomic risk assessment to guide the choice of postoperative therapy for many women with the most common type of primary breast cancer. The relative risk reduction with chemotherapy increased with increasing RS result.
Subsequent analyses of the TAILORx dataset, published in The New England Journal of Medicine and JAMA Oncology in 2019, examined the added effect of parameters of clinical risk (tumor size and grade) and patient age for patients with known genomic risk.
In these analyses, clinical risk was prognostic for recurrence but did not predict the absolute magnitude of chemotherapy benefit, regardless of age. There was a trend toward chemotherapy benefit in women who were younger than 50 years of age who had RS 21-15, but it was irrespective of clinical risk.
The development of RSClin
RSClin was derived from a patient-specific meta-analysis of 10,004 women with hormone receptor–positive, HER2-negative, node-negative breast cancer, of whom 9,427 participated in the TAILORx trial.
In TAILORx, which ran from 2006 to 2015, women with RS 0-11 received contemporary hormone therapy alone. Women with RS 12-25 were randomized to receive hormone therapy alone or with conventional combination chemotherapy. Women with RS above 26 received chemotherapy plus endocrine therapy.
The other patients in the meta-analysis participated in NSABP studies B-14 (tamoxifen versus placebo) and B-20 (tamoxifen versus chemotherapy plus tamoxifen).
Cox regression models were fit separately to each study with covariates of the continuous variables of RS result, tumor size, and patient age and the discrete variable of histologic tumor grade (assessed centrally in B-14 and in local laboratories in TAILORx). The prespecified endpoint was time to first distant recurrence.
RSClin estimates of distant recurrence risk were generated using baseline risk with TAILORx event rates to reflect current medical practice.
Model estimates were calculated for specified endocrine therapy with tamoxifen or aromatase inhibitors utilizing the treatment effect hazard ratio from an Early Breast Cancer Trialists’ Collaborative Group meta-analysis.
Patient-specific absolute benefit of chemotherapy was estimated by combining patient-specific meta-analysis risk estimates for distant recurrence and for relative chemotherapy benefit using the B-20 and TAILORx trials.
RSClin results and external validation
Among all patients in the meta-analysis cohort, RSClin provided a significantly more accurate prediction of distant recurrence events, in comparison with RS alone or clinical-pathologic factors alone.
External validation was performed using data from real-world outcomes from the 1,098 evaluable node-negative patients in the Clalit Health Services registry, of whom 876 received endocrine therapy alone and 222 received endocrine therapy plus chemotherapy.
RSClin estimates of distant recurrence closely approximated the observed risk in the registry (standardized hazard ratio, 1.73; 95% confidence interval, 1.40-2.15; P < .001). Within each RSClin risk quintile, the average 10-year risk estimate approached the observed Kaplan-Meier estimates in the cohort (Lin concordance correlation = 0.962).
Shared decision-making
For many years, the dilemma of whether to recommend adjuvant chemotherapy to a patient with early breast cancer has prompted the generation of tools to quantify a patient’s risk of recurrence and the magnitude of benefit for endocrine therapy and/or chemotherapy.
When the original Adjuvant! Online program was developed, genomic risk profiling was in its infancy. Genomic tools such as the 21-gene RS have subsequently demonstrated that they can help optimize the adjuvant treatment we recommend.
The RSClin tool provides more precise, individualized information than does clinical-pathological or genomic data alone. It prognosticates the risk of distant recurrence of breast cancer, which patients and providers fervently wish to minimize.
RSClin estimates the incremental benefit of contemporary adjuvant chemotherapy over modern endocrine therapy alone, in absolute values, for individual patients. This transparent, discrete, easily explained information is vital for counseling patients.
However, as highlighted in an editorial published in the Journal of Clinical Oncology, RSClin is not without its potential drawbacks. These include:
- Tumor heterogeneity leading to misleading results.
- Variable patient adherence to endocrine therapy or chemotherapy.
- The influence of comorbid conditions on the risk/benefit ratio.
- The potential of ovarian function suppression in young women to approach the magnitude of benefit associated with chemotherapy.
Accordingly, RSClin may be the latest and best available tool, but it will not be the last.
For patients with RS above 26, for older women with intermediate RS, and for younger women with a low RS and low clinical-pathologic features, RSClin may not influence treatment recommendations.
However, for the common scenario of an intermediate-risk RS and a mix of pathologic features, the accurate prognostication for distant recurrence risk and estimate of absolute benefit from chemotherapy will be terrifically helpful to oncology caregivers.
Dr. Sparano disclosed funding from the National Cancer Institute and travel support from Rhenium.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
When results of the TAILORx trial were presented at ASCO 2018, many oncologists thought it seemed too simple that a single number from a genomic assay could separate patients who would and would not benefit from adjuvant postoperative chemotherapy.
Those oncologists were right to be skeptical. Subsequent data indicated that better predictive tools were needed.
A new tool called “RSClin” may fit the bill. RSClin integrates the prognostic and predictive value of the 21-gene Oncotype DX recurrence score (RS) with the additional prognostic information conveyed by patient age, tumor grade, and tumor size.
RSClin provides individualized estimates of distant relapse risk for women with node-negative, endocrine sensitive, HER2/neu oncogene-negative early breast cancer – and a quantification of the additive freedom from distant relapse if that patient receives adjuvant chemotherapy. The tool is now available via a tab on the professional portal at https://online.genomichealth.com/.
Details on RSClin, including how the tool was developed and validated, were presented at the 2020 San Antonio Breast Cancer Symposium by Joseph A. Sparano, MD, of Albert Einstein College of Medicine in New York.
Beyond the initial publication of TAILORx
Results from the TAILORx trial published in The New England Journal of Medicine in 2018 offered the potential for genomic risk assessment to guide the choice of postoperative therapy for many women with the most common type of primary breast cancer. The relative risk reduction with chemotherapy increased with increasing RS result.
Subsequent analyses of the TAILORx dataset, published in The New England Journal of Medicine and JAMA Oncology in 2019, examined the added effect of parameters of clinical risk (tumor size and grade) and patient age for patients with known genomic risk.
In these analyses, clinical risk was prognostic for recurrence but did not predict the absolute magnitude of chemotherapy benefit, regardless of age. There was a trend toward chemotherapy benefit in women who were younger than 50 years of age who had RS 21-15, but it was irrespective of clinical risk.
The development of RSClin
RSClin was derived from a patient-specific meta-analysis of 10,004 women with hormone receptor–positive, HER2-negative, node-negative breast cancer, of whom 9,427 participated in the TAILORx trial.
In TAILORx, which ran from 2006 to 2015, women with RS 0-11 received contemporary hormone therapy alone. Women with RS 12-25 were randomized to receive hormone therapy alone or with conventional combination chemotherapy. Women with RS above 26 received chemotherapy plus endocrine therapy.
The other patients in the meta-analysis participated in NSABP studies B-14 (tamoxifen versus placebo) and B-20 (tamoxifen versus chemotherapy plus tamoxifen).
Cox regression models were fit separately to each study with covariates of the continuous variables of RS result, tumor size, and patient age and the discrete variable of histologic tumor grade (assessed centrally in B-14 and in local laboratories in TAILORx). The prespecified endpoint was time to first distant recurrence.
RSClin estimates of distant recurrence risk were generated using baseline risk with TAILORx event rates to reflect current medical practice.
Model estimates were calculated for specified endocrine therapy with tamoxifen or aromatase inhibitors utilizing the treatment effect hazard ratio from an Early Breast Cancer Trialists’ Collaborative Group meta-analysis.
Patient-specific absolute benefit of chemotherapy was estimated by combining patient-specific meta-analysis risk estimates for distant recurrence and for relative chemotherapy benefit using the B-20 and TAILORx trials.
RSClin results and external validation
Among all patients in the meta-analysis cohort, RSClin provided a significantly more accurate prediction of distant recurrence events, in comparison with RS alone or clinical-pathologic factors alone.
External validation was performed using data from real-world outcomes from the 1,098 evaluable node-negative patients in the Clalit Health Services registry, of whom 876 received endocrine therapy alone and 222 received endocrine therapy plus chemotherapy.
RSClin estimates of distant recurrence closely approximated the observed risk in the registry (standardized hazard ratio, 1.73; 95% confidence interval, 1.40-2.15; P < .001). Within each RSClin risk quintile, the average 10-year risk estimate approached the observed Kaplan-Meier estimates in the cohort (Lin concordance correlation = 0.962).
Shared decision-making
For many years, the dilemma of whether to recommend adjuvant chemotherapy to a patient with early breast cancer has prompted the generation of tools to quantify a patient’s risk of recurrence and the magnitude of benefit for endocrine therapy and/or chemotherapy.
When the original Adjuvant! Online program was developed, genomic risk profiling was in its infancy. Genomic tools such as the 21-gene RS have subsequently demonstrated that they can help optimize the adjuvant treatment we recommend.
The RSClin tool provides more precise, individualized information than does clinical-pathological or genomic data alone. It prognosticates the risk of distant recurrence of breast cancer, which patients and providers fervently wish to minimize.
RSClin estimates the incremental benefit of contemporary adjuvant chemotherapy over modern endocrine therapy alone, in absolute values, for individual patients. This transparent, discrete, easily explained information is vital for counseling patients.
However, as highlighted in an editorial published in the Journal of Clinical Oncology, RSClin is not without its potential drawbacks. These include:
- Tumor heterogeneity leading to misleading results.
- Variable patient adherence to endocrine therapy or chemotherapy.
- The influence of comorbid conditions on the risk/benefit ratio.
- The potential of ovarian function suppression in young women to approach the magnitude of benefit associated with chemotherapy.
Accordingly, RSClin may be the latest and best available tool, but it will not be the last.
For patients with RS above 26, for older women with intermediate RS, and for younger women with a low RS and low clinical-pathologic features, RSClin may not influence treatment recommendations.
However, for the common scenario of an intermediate-risk RS and a mix of pathologic features, the accurate prognostication for distant recurrence risk and estimate of absolute benefit from chemotherapy will be terrifically helpful to oncology caregivers.
Dr. Sparano disclosed funding from the National Cancer Institute and travel support from Rhenium.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
When results of the TAILORx trial were presented at ASCO 2018, many oncologists thought it seemed too simple that a single number from a genomic assay could separate patients who would and would not benefit from adjuvant postoperative chemotherapy.
Those oncologists were right to be skeptical. Subsequent data indicated that better predictive tools were needed.
A new tool called “RSClin” may fit the bill. RSClin integrates the prognostic and predictive value of the 21-gene Oncotype DX recurrence score (RS) with the additional prognostic information conveyed by patient age, tumor grade, and tumor size.
RSClin provides individualized estimates of distant relapse risk for women with node-negative, endocrine sensitive, HER2/neu oncogene-negative early breast cancer – and a quantification of the additive freedom from distant relapse if that patient receives adjuvant chemotherapy. The tool is now available via a tab on the professional portal at https://online.genomichealth.com/.
Details on RSClin, including how the tool was developed and validated, were presented at the 2020 San Antonio Breast Cancer Symposium by Joseph A. Sparano, MD, of Albert Einstein College of Medicine in New York.
Beyond the initial publication of TAILORx
Results from the TAILORx trial published in The New England Journal of Medicine in 2018 offered the potential for genomic risk assessment to guide the choice of postoperative therapy for many women with the most common type of primary breast cancer. The relative risk reduction with chemotherapy increased with increasing RS result.
Subsequent analyses of the TAILORx dataset, published in The New England Journal of Medicine and JAMA Oncology in 2019, examined the added effect of parameters of clinical risk (tumor size and grade) and patient age for patients with known genomic risk.
In these analyses, clinical risk was prognostic for recurrence but did not predict the absolute magnitude of chemotherapy benefit, regardless of age. There was a trend toward chemotherapy benefit in women who were younger than 50 years of age who had RS 21-15, but it was irrespective of clinical risk.
The development of RSClin
RSClin was derived from a patient-specific meta-analysis of 10,004 women with hormone receptor–positive, HER2-negative, node-negative breast cancer, of whom 9,427 participated in the TAILORx trial.
In TAILORx, which ran from 2006 to 2015, women with RS 0-11 received contemporary hormone therapy alone. Women with RS 12-25 were randomized to receive hormone therapy alone or with conventional combination chemotherapy. Women with RS above 26 received chemotherapy plus endocrine therapy.
The other patients in the meta-analysis participated in NSABP studies B-14 (tamoxifen versus placebo) and B-20 (tamoxifen versus chemotherapy plus tamoxifen).
Cox regression models were fit separately to each study with covariates of the continuous variables of RS result, tumor size, and patient age and the discrete variable of histologic tumor grade (assessed centrally in B-14 and in local laboratories in TAILORx). The prespecified endpoint was time to first distant recurrence.
RSClin estimates of distant recurrence risk were generated using baseline risk with TAILORx event rates to reflect current medical practice.
Model estimates were calculated for specified endocrine therapy with tamoxifen or aromatase inhibitors utilizing the treatment effect hazard ratio from an Early Breast Cancer Trialists’ Collaborative Group meta-analysis.
Patient-specific absolute benefit of chemotherapy was estimated by combining patient-specific meta-analysis risk estimates for distant recurrence and for relative chemotherapy benefit using the B-20 and TAILORx trials.
RSClin results and external validation
Among all patients in the meta-analysis cohort, RSClin provided a significantly more accurate prediction of distant recurrence events, in comparison with RS alone or clinical-pathologic factors alone.
External validation was performed using data from real-world outcomes from the 1,098 evaluable node-negative patients in the Clalit Health Services registry, of whom 876 received endocrine therapy alone and 222 received endocrine therapy plus chemotherapy.
RSClin estimates of distant recurrence closely approximated the observed risk in the registry (standardized hazard ratio, 1.73; 95% confidence interval, 1.40-2.15; P < .001). Within each RSClin risk quintile, the average 10-year risk estimate approached the observed Kaplan-Meier estimates in the cohort (Lin concordance correlation = 0.962).
Shared decision-making
For many years, the dilemma of whether to recommend adjuvant chemotherapy to a patient with early breast cancer has prompted the generation of tools to quantify a patient’s risk of recurrence and the magnitude of benefit for endocrine therapy and/or chemotherapy.
When the original Adjuvant! Online program was developed, genomic risk profiling was in its infancy. Genomic tools such as the 21-gene RS have subsequently demonstrated that they can help optimize the adjuvant treatment we recommend.
The RSClin tool provides more precise, individualized information than does clinical-pathological or genomic data alone. It prognosticates the risk of distant recurrence of breast cancer, which patients and providers fervently wish to minimize.
RSClin estimates the incremental benefit of contemporary adjuvant chemotherapy over modern endocrine therapy alone, in absolute values, for individual patients. This transparent, discrete, easily explained information is vital for counseling patients.
However, as highlighted in an editorial published in the Journal of Clinical Oncology, RSClin is not without its potential drawbacks. These include:
- Tumor heterogeneity leading to misleading results.
- Variable patient adherence to endocrine therapy or chemotherapy.
- The influence of comorbid conditions on the risk/benefit ratio.
- The potential of ovarian function suppression in young women to approach the magnitude of benefit associated with chemotherapy.
Accordingly, RSClin may be the latest and best available tool, but it will not be the last.
For patients with RS above 26, for older women with intermediate RS, and for younger women with a low RS and low clinical-pathologic features, RSClin may not influence treatment recommendations.
However, for the common scenario of an intermediate-risk RS and a mix of pathologic features, the accurate prognostication for distant recurrence risk and estimate of absolute benefit from chemotherapy will be terrifically helpful to oncology caregivers.
Dr. Sparano disclosed funding from the National Cancer Institute and travel support from Rhenium.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM SABCS 2020
Adaptive biomarker approach may spare some breast cancer patients chemo
The findings were reported at the 2020 San Antonio Breast Cancer Symposium.
“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.
Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.
The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.
The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.
At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
Similar outcomes
The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.
The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).
The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.
The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.
In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).
“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.
In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
Applying results to practice
“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.
“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.
The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).
“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.
Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.
“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”
Findings in context
More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.
“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.
Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).
And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.
“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”
The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.
The findings were reported at the 2020 San Antonio Breast Cancer Symposium.
“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.
Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.
The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.
The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.
At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
Similar outcomes
The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.
The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).
The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.
The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.
In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).
“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.
In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
Applying results to practice
“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.
“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.
The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).
“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.
Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.
“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”
Findings in context
More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.
“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.
Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).
And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.
“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”
The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.
The findings were reported at the 2020 San Antonio Breast Cancer Symposium.
“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.
Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.
The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.
The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.
At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
Similar outcomes
The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.
The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).
The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.
The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.
In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).
“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.
In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
Applying results to practice
“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.
“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.
The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).
“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.
Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.
“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”
Findings in context
More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.
“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.
Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).
And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.
“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”
The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.
FROM SABCS 2020
Entinostat doesn’t overcome endocrine resistance in advanced breast cancer
The study showed no difference in response, progression-free survival, or overall survival whether entinostat was added to exemestane or exemestane was given with placebo.
These results were reported at the 2020 San Antonio Breast Cancer Symposium.
“Clearly, we were very disappointed with these results after so many years of work,” said study investigator Roisin M. Connolly, MD, of University College Cork (Ireland) and Cork University Hospital in Wilton, Ireland.
“I think we’ve realized again the importance of phase 3 confirmation of promising phase 2 data,” she said, referring to results of the phase 2 ENCORE 301 trial.
“I think that the results speak for themselves. In this population of endocrine-resistant patients, the HDAC inhibitors clearly do not have a role unless we find something further on additional review of the correlative analyses,” Dr. Connolly said.
Why HDAC inhibitors in advanced breast cancer?
“Despite many advances in breast cancer in recent decades, resistance to endocrine therapy remains a significant clinical problem,” Dr. Connolly said.
One suggested approach to overcoming this resistance is to block the overacetylation of histones using HDAC inhibitors. This has been shown in preclinical studies with entinostat to inhibit growth factor signaling pathways and normalize the expression of the estrogen receptor, helping to overcome resistance to aromatase inhibitors in letrozole-resistant mouse models.
Results from the phase 2 ENCORE 301 trial, published in the Journal of Clinical Oncology, also suggested this approach could be effective. There was a 2-month improvement in progression-free survival and an 8.3-month improvement in overall survival when entinostat was added to exemestane.
Phase 3 trial details and results
The E2112 study enrolled 608 women with hormone receptor–positive, HER2-negative advanced breast cancer, 85% of whom had experienced progression after taking a nonsteroidal aromatase inhibitor in the metastatic setting.
The type of endocrine resistance, such as if ESR1 mutations were present, was not determined. Tissue samples and blood samples have been archived, so this might be a question that is investigated later on.
A quarter of patients had received one prior chemotherapy regimen for metastatic disease, around 30% had been treated with fulvestrant, and about a third of patients had received a CDK4/6 inhibitor.
“I think we had representation from both patients who did receive and did not receive a prior CDK4/6 inhibitor within E2112,” Dr. Connolly said, observing that the study started in 2014 before the use of these drugs was really established.
Patients were randomized to receive entinostat (5 mg daily) plus exemestane (25 mg daily) or exemestane plus placebo (at the same dose).
The median progression-free survival was 3.3 months in the entinostat arm and 3.1 months in the placebo arm (hazard ratio, 0.87; P = .30).
The median overall survival was 23.4 months with entinostat and 21.7 months with placebo (HR, 0.99; P = .94). The overall response rates were a respective 4.6% and 4.3%.
Grade 3/4 adverse events were more frequent in the entinostat arm. The most common were neutropenia (20% with entinostat vs. <1% with placebo), hypophosphatemia (14% vs. 1%), and anemia (8% vs. 2%).
There were three treatment-related deaths (heart failure, pneumonitis, and hepatic failure) in the entinostat arm and one (MI) in the placebo arm.
Implications and next steps
“The study is completely negative, with no benefit in progression-free or overall survival,” commented Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the study.
“It is unclear that this is a good clinical approach for further trials in advanced breast cancer, as correlative studies suggest the drug did hit the target,” he added.
Dr. Burstein’s takeaway was that “HDAC inhibition is stuck in a cul-de-sac, if not a complete dead end, for breast cancer.”
When asked if using a different aromatase inhibitor than exemestane might have affected the results, Dr. Connolly said that “it’s possible, but I think it’s unlikely.”
Exemestane was used in the phase 3 trial because it had been used in the ENCORE 301 study. Preclinical work had shown that both letrozole- and exemestane-resistant models benefited from the addition of an HDAC inhibitor.
“There is ongoing investigation of HDAC inhibitors in various combinations,” Dr. Connolly said. “HDAC inhibitors have been used with chemotherapies and other targeted therapies over the years but unfortunately have not broken into the solid tumor space. I think that ongoing work will be required to see where these may fit in the future.”
The E2122 study was coordinated by the ECOG-ACRIN Cancer Research Group with funding from the National Institutes of Health. Dr. Connolly disclosed relationships with Genentech, Merck, Novartis, Puma Biotechnology, Marcogenics, and Pfizer. Dr. Burstein had no relevant disclosures.
The study showed no difference in response, progression-free survival, or overall survival whether entinostat was added to exemestane or exemestane was given with placebo.
These results were reported at the 2020 San Antonio Breast Cancer Symposium.
“Clearly, we were very disappointed with these results after so many years of work,” said study investigator Roisin M. Connolly, MD, of University College Cork (Ireland) and Cork University Hospital in Wilton, Ireland.
“I think we’ve realized again the importance of phase 3 confirmation of promising phase 2 data,” she said, referring to results of the phase 2 ENCORE 301 trial.
“I think that the results speak for themselves. In this population of endocrine-resistant patients, the HDAC inhibitors clearly do not have a role unless we find something further on additional review of the correlative analyses,” Dr. Connolly said.
Why HDAC inhibitors in advanced breast cancer?
“Despite many advances in breast cancer in recent decades, resistance to endocrine therapy remains a significant clinical problem,” Dr. Connolly said.
One suggested approach to overcoming this resistance is to block the overacetylation of histones using HDAC inhibitors. This has been shown in preclinical studies with entinostat to inhibit growth factor signaling pathways and normalize the expression of the estrogen receptor, helping to overcome resistance to aromatase inhibitors in letrozole-resistant mouse models.
Results from the phase 2 ENCORE 301 trial, published in the Journal of Clinical Oncology, also suggested this approach could be effective. There was a 2-month improvement in progression-free survival and an 8.3-month improvement in overall survival when entinostat was added to exemestane.
Phase 3 trial details and results
The E2112 study enrolled 608 women with hormone receptor–positive, HER2-negative advanced breast cancer, 85% of whom had experienced progression after taking a nonsteroidal aromatase inhibitor in the metastatic setting.
The type of endocrine resistance, such as if ESR1 mutations were present, was not determined. Tissue samples and blood samples have been archived, so this might be a question that is investigated later on.
A quarter of patients had received one prior chemotherapy regimen for metastatic disease, around 30% had been treated with fulvestrant, and about a third of patients had received a CDK4/6 inhibitor.
“I think we had representation from both patients who did receive and did not receive a prior CDK4/6 inhibitor within E2112,” Dr. Connolly said, observing that the study started in 2014 before the use of these drugs was really established.
Patients were randomized to receive entinostat (5 mg daily) plus exemestane (25 mg daily) or exemestane plus placebo (at the same dose).
The median progression-free survival was 3.3 months in the entinostat arm and 3.1 months in the placebo arm (hazard ratio, 0.87; P = .30).
The median overall survival was 23.4 months with entinostat and 21.7 months with placebo (HR, 0.99; P = .94). The overall response rates were a respective 4.6% and 4.3%.
Grade 3/4 adverse events were more frequent in the entinostat arm. The most common were neutropenia (20% with entinostat vs. <1% with placebo), hypophosphatemia (14% vs. 1%), and anemia (8% vs. 2%).
There were three treatment-related deaths (heart failure, pneumonitis, and hepatic failure) in the entinostat arm and one (MI) in the placebo arm.
Implications and next steps
“The study is completely negative, with no benefit in progression-free or overall survival,” commented Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the study.
“It is unclear that this is a good clinical approach for further trials in advanced breast cancer, as correlative studies suggest the drug did hit the target,” he added.
Dr. Burstein’s takeaway was that “HDAC inhibition is stuck in a cul-de-sac, if not a complete dead end, for breast cancer.”
When asked if using a different aromatase inhibitor than exemestane might have affected the results, Dr. Connolly said that “it’s possible, but I think it’s unlikely.”
Exemestane was used in the phase 3 trial because it had been used in the ENCORE 301 study. Preclinical work had shown that both letrozole- and exemestane-resistant models benefited from the addition of an HDAC inhibitor.
“There is ongoing investigation of HDAC inhibitors in various combinations,” Dr. Connolly said. “HDAC inhibitors have been used with chemotherapies and other targeted therapies over the years but unfortunately have not broken into the solid tumor space. I think that ongoing work will be required to see where these may fit in the future.”
The E2122 study was coordinated by the ECOG-ACRIN Cancer Research Group with funding from the National Institutes of Health. Dr. Connolly disclosed relationships with Genentech, Merck, Novartis, Puma Biotechnology, Marcogenics, and Pfizer. Dr. Burstein had no relevant disclosures.
The study showed no difference in response, progression-free survival, or overall survival whether entinostat was added to exemestane or exemestane was given with placebo.
These results were reported at the 2020 San Antonio Breast Cancer Symposium.
“Clearly, we were very disappointed with these results after so many years of work,” said study investigator Roisin M. Connolly, MD, of University College Cork (Ireland) and Cork University Hospital in Wilton, Ireland.
“I think we’ve realized again the importance of phase 3 confirmation of promising phase 2 data,” she said, referring to results of the phase 2 ENCORE 301 trial.
“I think that the results speak for themselves. In this population of endocrine-resistant patients, the HDAC inhibitors clearly do not have a role unless we find something further on additional review of the correlative analyses,” Dr. Connolly said.
Why HDAC inhibitors in advanced breast cancer?
“Despite many advances in breast cancer in recent decades, resistance to endocrine therapy remains a significant clinical problem,” Dr. Connolly said.
One suggested approach to overcoming this resistance is to block the overacetylation of histones using HDAC inhibitors. This has been shown in preclinical studies with entinostat to inhibit growth factor signaling pathways and normalize the expression of the estrogen receptor, helping to overcome resistance to aromatase inhibitors in letrozole-resistant mouse models.
Results from the phase 2 ENCORE 301 trial, published in the Journal of Clinical Oncology, also suggested this approach could be effective. There was a 2-month improvement in progression-free survival and an 8.3-month improvement in overall survival when entinostat was added to exemestane.
Phase 3 trial details and results
The E2112 study enrolled 608 women with hormone receptor–positive, HER2-negative advanced breast cancer, 85% of whom had experienced progression after taking a nonsteroidal aromatase inhibitor in the metastatic setting.
The type of endocrine resistance, such as if ESR1 mutations were present, was not determined. Tissue samples and blood samples have been archived, so this might be a question that is investigated later on.
A quarter of patients had received one prior chemotherapy regimen for metastatic disease, around 30% had been treated with fulvestrant, and about a third of patients had received a CDK4/6 inhibitor.
“I think we had representation from both patients who did receive and did not receive a prior CDK4/6 inhibitor within E2112,” Dr. Connolly said, observing that the study started in 2014 before the use of these drugs was really established.
Patients were randomized to receive entinostat (5 mg daily) plus exemestane (25 mg daily) or exemestane plus placebo (at the same dose).
The median progression-free survival was 3.3 months in the entinostat arm and 3.1 months in the placebo arm (hazard ratio, 0.87; P = .30).
The median overall survival was 23.4 months with entinostat and 21.7 months with placebo (HR, 0.99; P = .94). The overall response rates were a respective 4.6% and 4.3%.
Grade 3/4 adverse events were more frequent in the entinostat arm. The most common were neutropenia (20% with entinostat vs. <1% with placebo), hypophosphatemia (14% vs. 1%), and anemia (8% vs. 2%).
There were three treatment-related deaths (heart failure, pneumonitis, and hepatic failure) in the entinostat arm and one (MI) in the placebo arm.
Implications and next steps
“The study is completely negative, with no benefit in progression-free or overall survival,” commented Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the study.
“It is unclear that this is a good clinical approach for further trials in advanced breast cancer, as correlative studies suggest the drug did hit the target,” he added.
Dr. Burstein’s takeaway was that “HDAC inhibition is stuck in a cul-de-sac, if not a complete dead end, for breast cancer.”
When asked if using a different aromatase inhibitor than exemestane might have affected the results, Dr. Connolly said that “it’s possible, but I think it’s unlikely.”
Exemestane was used in the phase 3 trial because it had been used in the ENCORE 301 study. Preclinical work had shown that both letrozole- and exemestane-resistant models benefited from the addition of an HDAC inhibitor.
“There is ongoing investigation of HDAC inhibitors in various combinations,” Dr. Connolly said. “HDAC inhibitors have been used with chemotherapies and other targeted therapies over the years but unfortunately have not broken into the solid tumor space. I think that ongoing work will be required to see where these may fit in the future.”
The E2122 study was coordinated by the ECOG-ACRIN Cancer Research Group with funding from the National Institutes of Health. Dr. Connolly disclosed relationships with Genentech, Merck, Novartis, Puma Biotechnology, Marcogenics, and Pfizer. Dr. Burstein had no relevant disclosures.
FROM SABCS 2020
One-week radiotherapy course should be standard for early invasive breast cancer, experts say
The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.
The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.
These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.
Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.
The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.
“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.
FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
Relapse, safety, and patient reports
The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.
The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).
The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.
In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).
Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.
However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.
Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
A new standard
“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”
“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”
“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.
Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”
“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.
“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”
FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.
SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.
The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.
The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.
These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.
Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.
The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.
“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.
FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
Relapse, safety, and patient reports
The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.
The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).
The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.
In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).
Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.
However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.
Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
A new standard
“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”
“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”
“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.
Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”
“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.
“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”
FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.
SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.
The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.
The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.
These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.
Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.
The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.
“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.
FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
Relapse, safety, and patient reports
The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.
The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).
The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.
In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).
Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.
However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.
Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
A new standard
“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”
“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”
“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.
Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”
“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.
“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”
FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.
SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.
FROM ESTRO 2020
After 48 years, NCI aims to track breast cancer recurrences
Change to SEER eventually planned.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
Change to SEER eventually planned.
Change to SEER eventually planned.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
Clinical Edge Commentary: Breast Cancer January 2021
Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.
The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.
Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.
References:
Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.
Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.
King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.
Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.
Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.
Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.
The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.
Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.
References:
Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.
Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.
King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.
Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.
Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.
Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.
The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.
Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.
References:
Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.
Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.
King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.
Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.
Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.
Omitting postop radiotherapy doesn’t affect survival in older breast cancer patients
Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.
Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).
Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).
Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.
Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.
Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.
Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).
Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).
Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.
Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.
Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.
Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).
Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).
Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.
Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.
PENELOPE-B: Palbociclib disappoints in HR+, HER2– breast cancer
Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.
Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).
Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.
Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.
Source: Loibl S et al. SABCS 2020, Abstract GS1-02.
Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.
Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).
Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.
Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.
Source: Loibl S et al. SABCS 2020, Abstract GS1-02.
Key clinical point: One year of palbociclib added to endocrine therapy after neoadjuvant chemotherapy did not improve invasive disease-free survival when compared with placebo plus endocrine therapy in women with hormone receptor–positive, HER2-negative primary breast cancer.
Major finding: The 4-year invasive disease-free survival rate was 73.0% for palbociclib and 72.4% for placebo (hazard ratio, 0.93; P = .525).
Study details: A phase 3 trial of 1,250 women with hormone receptor–positive, HER2-negative primary breast cancer who were at high risk of relapse after neoadjuvant chemotherapy.
Disclosures: The trial was sponsored by the German Breast Group in collaboration with Pfizer, the AGO Study Group, NSABP Foundation, and the Breast International Group. Dr. Loibl disclosed grant and other support from Pfizer during the conduct of the study, relationships with other companies outside the submitted work, a pending patent for a method to predict response to anti-HER2–containing therapy and/or chemotherapy, and a relationship with Medscape, which is owned by the same company as MDedge.
Source: Loibl S et al. SABCS 2020, Abstract GS1-02.