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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