TAILORx marks major advance for precision medicine in breast cancer

 

CHICAGO – Use of the 21–tumor gene expression assay (Oncotype DX Recurrence Score) allows nearly 70% of women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer to safely forgo adjuvant chemotherapy, sparing them adverse effects and preventing overtreatment, TAILORx trial results show.

The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.

Susan London/MDedge News

“The rationale for the TAILORx precision medicine trial is that we are really trying to ‘thread the needle,’ ” lead study author Joseph A. Sparano, MD, associate director for clinical research at Albert Einstein Cancer Center and Montefiore Health System in New York, and vice chair of the ECOG-ACRIN Cancer Research Group, explained in a press briefing. Oncologists typically recommend adjuvant chemotherapy for the half of all breast cancers that are hormone receptor positive, HER2 negative, and node negative, even though its absolute benefit in reducing recurrences in this population is small. “This results in most patients being overtreated because endocrine therapy alone is adequate. But some are undertreated: They do not receive chemotherapy but could have benefited from it,” he noted.

The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”

The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.

Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.

The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.

 

Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”

In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).

Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).

“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”

 

An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.

Tailoring treatment: ‘not too much and not too little’

“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”

Susan London/MDedge News

The recurrence score has been used for a decade, so some may wonder why this trial was necessary. It was important because the score was originally developed in patients given older chemotherapy regimens and older endocrine therapies, and because there have been few data to guide decision making in the large group of patients with midrange scores, he said. “A criticism of the older literature had been, well, chemotherapy didn’t help but that’s because we were using old-fashioned chemo. Now we can say with confidence ... that the patients got contemporary chemo regimens and still saw no benefit from chemotherapy.

“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.

 

“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”

Study details

All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.

Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.

Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”

 

Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.

The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).

In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.

The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.

Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.

SOURCE: Sparano et al. ASCO 2018 Abstract LBA1

 

CHICAGO – Use of the 21–tumor gene expression assay (Oncotype DX Recurrence Score) allows nearly 70% of women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer to safely forgo adjuvant chemotherapy, sparing them adverse effects and preventing overtreatment, TAILORx trial results show.

The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.

Susan London/MDedge News

“The rationale for the TAILORx precision medicine trial is that we are really trying to ‘thread the needle,’ ” lead study author Joseph A. Sparano, MD, associate director for clinical research at Albert Einstein Cancer Center and Montefiore Health System in New York, and vice chair of the ECOG-ACRIN Cancer Research Group, explained in a press briefing. Oncologists typically recommend adjuvant chemotherapy for the half of all breast cancers that are hormone receptor positive, HER2 negative, and node negative, even though its absolute benefit in reducing recurrences in this population is small. “This results in most patients being overtreated because endocrine therapy alone is adequate. But some are undertreated: They do not receive chemotherapy but could have benefited from it,” he noted.

The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”

The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.

Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.

The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.

 

Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”

In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).

Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).

“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”

 

An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.

Tailoring treatment: ‘not too much and not too little’

“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”

Susan London/MDedge News

The recurrence score has been used for a decade, so some may wonder why this trial was necessary. It was important because the score was originally developed in patients given older chemotherapy regimens and older endocrine therapies, and because there have been few data to guide decision making in the large group of patients with midrange scores, he said. “A criticism of the older literature had been, well, chemotherapy didn’t help but that’s because we were using old-fashioned chemo. Now we can say with confidence ... that the patients got contemporary chemo regimens and still saw no benefit from chemotherapy.

“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.

 

“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”

Study details

All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.

Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.

Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”

 

Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.

The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).

In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.

The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.

Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.

SOURCE: Sparano et al. ASCO 2018 Abstract LBA1

 

CHICAGO – Use of the 21–tumor gene expression assay (Oncotype DX Recurrence Score) allows nearly 70% of women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer to safely forgo adjuvant chemotherapy, sparing them adverse effects and preventing overtreatment, TAILORx trial results show.

The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.

Susan London/MDedge News

“The rationale for the TAILORx precision medicine trial is that we are really trying to ‘thread the needle,’ ” lead study author Joseph A. Sparano, MD, associate director for clinical research at Albert Einstein Cancer Center and Montefiore Health System in New York, and vice chair of the ECOG-ACRIN Cancer Research Group, explained in a press briefing. Oncologists typically recommend adjuvant chemotherapy for the half of all breast cancers that are hormone receptor positive, HER2 negative, and node negative, even though its absolute benefit in reducing recurrences in this population is small. “This results in most patients being overtreated because endocrine therapy alone is adequate. But some are undertreated: They do not receive chemotherapy but could have benefited from it,” he noted.

The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”

The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.

Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.

The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.

 

Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”

In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).

Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).

“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”

 

An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.

Tailoring treatment: ‘not too much and not too little’

“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”

Susan London/MDedge News

The recurrence score has been used for a decade, so some may wonder why this trial was necessary. It was important because the score was originally developed in patients given older chemotherapy regimens and older endocrine therapies, and because there have been few data to guide decision making in the large group of patients with midrange scores, he said. “A criticism of the older literature had been, well, chemotherapy didn’t help but that’s because we were using old-fashioned chemo. Now we can say with confidence ... that the patients got contemporary chemo regimens and still saw no benefit from chemotherapy.

“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.

 

“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”

Study details

All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.

Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.

Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”

 

Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.

The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).

In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.

The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.

Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.

SOURCE: Sparano et al. ASCO 2018 Abstract LBA1