Breast Cancer

Background Multicenter clinical trials conducted primarily at academic centers have shown that breast-conserving therapy (BCT) and mastectomy lead to equivalent overall survival (OS) for women with early-stage breast cancer.

Objective To determine rates of BCT and OS after conservation therapy in a large urban community practice, compare them with national rates, and identify risk factors for survival.

Methods We identified 1,172 T1-2, N0 breast cancer patients diagnosed during 1997-2007 in our hospital tumor registry and compared the rates of BCT and adjuvant radiotherapy with a similar population in the SEER [Surveillance, Epidemiology, and End Results] database (N = 232,898) for the same treatment period. Cox proportional hazards models were used to assess the influence of age at diagnosis, tumor grade, biomarker status, margin status, and receipt of hormones, radiation, or chemotherapy on OS after BCT.

Results The rate of breast-conserving surgery (BCS) was higher in our practice compared with the national average (90.9% and 66.4%, respectively). The rate of adjuvant radiation after BCS in our practice was 93.7%; survival estimates were higher for patients treated with adjuvant radiation across all age groups, compared with the national estimates (92.5% and 72.9%). Younger age and receipt of radiation were associated with improved survival.

Limitations Retrospective study design; confounding factors such as comorbidities were not considered.

Conclusions We had high rates of BCT and adjuvant radiation in early-stage breast cancer patients in our community practice, which resulted in excellent survival rates that compared favorably with those in large academic centers and emphasizes the role of appropriate use of adjuvant radiation.

Funding Vantage Oncology

Click on the PDF icon at the top of this introduction to read the full article.

Background Multicenter clinical trials conducted primarily at academic centers have shown that breast-conserving therapy (BCT) and mastectomy lead to equivalent overall survival (OS) for women with early-stage breast cancer.

Objective To determine rates of BCT and OS after conservation therapy in a large urban community practice, compare them with national rates, and identify risk factors for survival.

Methods We identified 1,172 T1-2, N0 breast cancer patients diagnosed during 1997-2007 in our hospital tumor registry and compared the rates of BCT and adjuvant radiotherapy with a similar population in the SEER [Surveillance, Epidemiology, and End Results] database (N = 232,898) for the same treatment period. Cox proportional hazards models were used to assess the influence of age at diagnosis, tumor grade, biomarker status, margin status, and receipt of hormones, radiation, or chemotherapy on OS after BCT.

Results The rate of breast-conserving surgery (BCS) was higher in our practice compared with the national average (90.9% and 66.4%, respectively). The rate of adjuvant radiation after BCS in our practice was 93.7%; survival estimates were higher for patients treated with adjuvant radiation across all age groups, compared with the national estimates (92.5% and 72.9%). Younger age and receipt of radiation were associated with improved survival.

Limitations Retrospective study design; confounding factors such as comorbidities were not considered.

Conclusions We had high rates of BCT and adjuvant radiation in early-stage breast cancer patients in our community practice, which resulted in excellent survival rates that compared favorably with those in large academic centers and emphasizes the role of appropriate use of adjuvant radiation.

Funding Vantage Oncology

Click on the PDF icon at the top of this introduction to read the full article.

Background Multicenter clinical trials conducted primarily at academic centers have shown that breast-conserving therapy (BCT) and mastectomy lead to equivalent overall survival (OS) for women with early-stage breast cancer.

Objective To determine rates of BCT and OS after conservation therapy in a large urban community practice, compare them with national rates, and identify risk factors for survival.

Methods We identified 1,172 T1-2, N0 breast cancer patients diagnosed during 1997-2007 in our hospital tumor registry and compared the rates of BCT and adjuvant radiotherapy with a similar population in the SEER [Surveillance, Epidemiology, and End Results] database (N = 232,898) for the same treatment period. Cox proportional hazards models were used to assess the influence of age at diagnosis, tumor grade, biomarker status, margin status, and receipt of hormones, radiation, or chemotherapy on OS after BCT.

Results The rate of breast-conserving surgery (BCS) was higher in our practice compared with the national average (90.9% and 66.4%, respectively). The rate of adjuvant radiation after BCS in our practice was 93.7%; survival estimates were higher for patients treated with adjuvant radiation across all age groups, compared with the national estimates (92.5% and 72.9%). Younger age and receipt of radiation were associated with improved survival.

Limitations Retrospective study design; confounding factors such as comorbidities were not considered.

Conclusions We had high rates of BCT and adjuvant radiation in early-stage breast cancer patients in our community practice, which resulted in excellent survival rates that compared favorably with those in large academic centers and emphasizes the role of appropriate use of adjuvant radiation.

Funding Vantage Oncology

Click on the PDF icon at the top of this introduction to read the full article.

Yes: MRI should be considered in the preoperative setting for specific clinical indications.

MRI, like any technology, has its strengths and weaknesses, with high sensitivity but low specificity. Importantly, MRI provides excellent soft tissue contrast with anatomic 3-D detail, and is not impeded by high breast density.

Admittedly, MRI only incrementally increases cancer detection rates in either the ipsilateral or contralateral breasts of all patients, and when used in the preoperative setting does not affect short-term surgical outcomes for all patients. Therefore, MRI should not be used for routine screening or routine preoperative screening.

That said, there are specific clinical situations where preoperative MRI may provide surgeons with valuable information. These include patients who have:

• Invasive lobular carcinoma.

• Neoadjuvant chemotherapy.

• Occult primaries in extremely dense breasts.

Invasive lobular carcinomas are more likely to be multi-centric, multi-focal, and/or bilateral than other breast cancer types, and they are more difficult to diagnose because they infiltrate into tissue, making it extremely difficult to determine the extent of disease. In this setting, MRI can more accurately determine tumor size than mammography. Mammography underestimates the tumor size significantly more frequently than does MRI. In addition, among women with this cancer subtype, MRI can significantly reduce the rate of excision (Breast Cancer Res Treat. 2010;119;415-22).

We know that women at risk for systemic recurrence will not be cured with surgery alone. Neoadjuvant therapies give us the opportunity to refine local therapy options, better understand the patient’s response to therapy and prognosis, and accelerate targeted drug development to improve outcomes. To accomplish all of these goals, we need a noninvasive way to assess tumors before, during, and after neoadjuvant treatment. MRI is unsurpassed for evaluating the extent of tumors, showing in larger tumors, for example, the complexity of tumor and stroma.

MRI is also a biomarker for response to therapy and has been shown to be an independent predictor of event-free survival. In addition, MRI is more accurate than either clinical exam, mammography, or ultrasound for determining residual tumor size following neoadjuvant chemotherapy (Radiology. 2012;263:663-72).

Lastly, for patients with an occult primary (by imaging) breast cancer or primary presentation of axillary node involvement, MRI has been found to have an approximately 90% sensitivity for identifying a primary tumor, and a 95% accuracy at locating the tumor in patients who undergo surgical excision. Mammography cannot distinguish a tumor mass that is dense relative to surrounding tissue. However, MRI can distinguish a tumor which is obscured by dense breast tissue because tumors are visualized on MRI by rapid contrast uptake and washout.

MRI is a catalyst for change, but you have to use it and all technology wisely: At the time of diagnosis for select patients, for screening only those patients with very breast dense tissue and very high risk for developing breast cancer, and, perhaps most importantly, for postcancer surveillance only in women at very high risk of recurrence where standard tools such as mammography are expected to have lower performance (for example, very dense breast tissue). Overuse of MRI will increase false positives, anxiety, and cost. However, used appropriately, MRI can be used to help usher in a change in practice through the evaluation of response to neoadjuvant therapy and novel therapeutic approaches to both invasive and in situ lesions.

With improvements in technology and techniques such as diffusion-weighted imaging, the value of MRI in the preoperative setting can only continue to grow. We can also expect greater performance for presurgical staging with more refined technologies for breast imaging, localization, and biopsy, but the costs have to come down. Breast-dedicated MRI technologies may address this need.

Laura Esserman, MD, is a professor of surgery and radiology at the University of California, San Francisco, and Director of the Carol Franc Buck Breast Care Center at the UCSF Mount Zion campus.

No: MRI leads to unnecessary surgeries and does not improve short-term surgical outcomes.

The key word in this debate is “routinely.” I agree that preoperative MRI may have a role in about 5% of all cases – namely in women with occult primaries and those who undergo neoadjuvant chemotherapy. But for the vast majority of patients, the 95%, I would argue that preoperative MRI has the potential to do more harm than good.

Thirty years of experience providing breast conserving therapies without MRI has taught us several important lessons:

• Selection of patients for breast-conserving therapy is not a big problem.

• The incidences of local recurrence and contralateral breast cancers have decreased over time, antedating the use of MRI.

• Surgical excision of all microscopic subclinical disease is not necessary to achieve good long-term outcomes.

In National Surgical Adjuvant Breast and Bowel Project studies from the 1990s, in the era before the use of aromatase inhibitors or HER-2 blockade, the 10-year incidence of ipsilateral breast tumor recurrence ranged from 3.5% to 6.5% in the breast cancer population at large.

In addition, the incidence of contralateral breast cancers has been declining at a rate of approximately 3% per year, thanks to the use of adjuvant systemic therapies.

We have known since the 1960s, thanks to our colleagues in pathology, that somewhere between 30% and 60% of breast cancers that appear to be localized have microscopic subclinical disease which is treated with breast irradiation. More recently, we have recognized that we can leave behind cancer in the axilla in anywhere from 13% to 27% of patients who are not receiving direct axillary radiation, and see failure rates of 1% or less.

In the context, then, of our current understanding of breast cancer biology, what outcomes could MRI be expected to improve, since the purpose of a test is to improve patient outcomes?

We know that MRI will not improve survival, because 30 years ago randomized trials showed us that survival was equal between breast conservation and mastectomy.

MRI has no apparent effect on reducing local recurrences either, as shown in an analysis of data on 3,180 patients published in 2014 (J Clin Oncol. 2014;32:292).

Regarding contralateral breast cancer, a 2007 study (N Engl J Med. 2007;356:1295-303) showed that among 969 women, MRI found unsuspected cancer in the contralateral breast within 1 year of diagnosis in 3.1%, a finding used to support the argument that all women with breast cancer should have an MRI. But a second study using Surveillance, Epidemiology and End Results (SEER) data on 339,790 women with 2.5 million person-years of follow-up found that the 10-year rate of contralateral cancers was 2%-3% of women with estrogen-receptor–positive tumors, and in 5%-6% of those with estrogen-receptor–negative tumors, strongly suggesting that MRI leads to detection and treatment of disease that would never become clinically evident.

Finally, I would point to evidence that MRI does not improve short-term surgical outcomes, as shown in a meta-analysis my colleagues and I conducted of two randomized controlled trials and seven cohort studies, involving a total of 3,112 patients (Ann Surg. 2013;257:249-55).

We found that after adjustment for age, having an MRI was associated with a three-fold greater chance of having a mastectomy, and MRI did not significantly reduce either the need for re-excision or unexpected conversion to mastectomy. We also performed a subanalysis of infiltrating lobular cancers, and found that there was no statistically significant benefit for MRI in these patients.

The overall rate of mastectomy was 25.5% among patients who had an MRI, vs. 18.2% for those who did not.

So to summarize: MRI finds two to three times more cancer than observed rates of local recurrence, leading to unnecessary mastectomies and does not improve short-term surgical outcomes, and there is no evidence indicating that MRI decreases local recurrence.

Monica Morrow, MD, FACS, is chief of the breast service in the department of surgery and holds the Anne Burnett Windfohr Chair of Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York.

Yes: MRI should be considered in the preoperative setting for specific clinical indications.

MRI, like any technology, has its strengths and weaknesses, with high sensitivity but low specificity. Importantly, MRI provides excellent soft tissue contrast with anatomic 3-D detail, and is not impeded by high breast density.

Admittedly, MRI only incrementally increases cancer detection rates in either the ipsilateral or contralateral breasts of all patients, and when used in the preoperative setting does not affect short-term surgical outcomes for all patients. Therefore, MRI should not be used for routine screening or routine preoperative screening.

That said, there are specific clinical situations where preoperative MRI may provide surgeons with valuable information. These include patients who have:

• Invasive lobular carcinoma.

• Neoadjuvant chemotherapy.

• Occult primaries in extremely dense breasts.

Invasive lobular carcinomas are more likely to be multi-centric, multi-focal, and/or bilateral than other breast cancer types, and they are more difficult to diagnose because they infiltrate into tissue, making it extremely difficult to determine the extent of disease. In this setting, MRI can more accurately determine tumor size than mammography. Mammography underestimates the tumor size significantly more frequently than does MRI. In addition, among women with this cancer subtype, MRI can significantly reduce the rate of excision (Breast Cancer Res Treat. 2010;119;415-22).

We know that women at risk for systemic recurrence will not be cured with surgery alone. Neoadjuvant therapies give us the opportunity to refine local therapy options, better understand the patient’s response to therapy and prognosis, and accelerate targeted drug development to improve outcomes. To accomplish all of these goals, we need a noninvasive way to assess tumors before, during, and after neoadjuvant treatment. MRI is unsurpassed for evaluating the extent of tumors, showing in larger tumors, for example, the complexity of tumor and stroma.

MRI is also a biomarker for response to therapy and has been shown to be an independent predictor of event-free survival. In addition, MRI is more accurate than either clinical exam, mammography, or ultrasound for determining residual tumor size following neoadjuvant chemotherapy (Radiology. 2012;263:663-72).

Lastly, for patients with an occult primary (by imaging) breast cancer or primary presentation of axillary node involvement, MRI has been found to have an approximately 90% sensitivity for identifying a primary tumor, and a 95% accuracy at locating the tumor in patients who undergo surgical excision. Mammography cannot distinguish a tumor mass that is dense relative to surrounding tissue. However, MRI can distinguish a tumor which is obscured by dense breast tissue because tumors are visualized on MRI by rapid contrast uptake and washout.

MRI is a catalyst for change, but you have to use it and all technology wisely: At the time of diagnosis for select patients, for screening only those patients with very breast dense tissue and very high risk for developing breast cancer, and, perhaps most importantly, for postcancer surveillance only in women at very high risk of recurrence where standard tools such as mammography are expected to have lower performance (for example, very dense breast tissue). Overuse of MRI will increase false positives, anxiety, and cost. However, used appropriately, MRI can be used to help usher in a change in practice through the evaluation of response to neoadjuvant therapy and novel therapeutic approaches to both invasive and in situ lesions.

With improvements in technology and techniques such as diffusion-weighted imaging, the value of MRI in the preoperative setting can only continue to grow. We can also expect greater performance for presurgical staging with more refined technologies for breast imaging, localization, and biopsy, but the costs have to come down. Breast-dedicated MRI technologies may address this need.

Laura Esserman, MD, is a professor of surgery and radiology at the University of California, San Francisco, and Director of the Carol Franc Buck Breast Care Center at the UCSF Mount Zion campus.

No: MRI leads to unnecessary surgeries and does not improve short-term surgical outcomes.

The key word in this debate is “routinely.” I agree that preoperative MRI may have a role in about 5% of all cases – namely in women with occult primaries and those who undergo neoadjuvant chemotherapy. But for the vast majority of patients, the 95%, I would argue that preoperative MRI has the potential to do more harm than good.

Thirty years of experience providing breast conserving therapies without MRI has taught us several important lessons:

• Selection of patients for breast-conserving therapy is not a big problem.

• The incidences of local recurrence and contralateral breast cancers have decreased over time, antedating the use of MRI.

• Surgical excision of all microscopic subclinical disease is not necessary to achieve good long-term outcomes.

In National Surgical Adjuvant Breast and Bowel Project studies from the 1990s, in the era before the use of aromatase inhibitors or HER-2 blockade, the 10-year incidence of ipsilateral breast tumor recurrence ranged from 3.5% to 6.5% in the breast cancer population at large.

In addition, the incidence of contralateral breast cancers has been declining at a rate of approximately 3% per year, thanks to the use of adjuvant systemic therapies.

We have known since the 1960s, thanks to our colleagues in pathology, that somewhere between 30% and 60% of breast cancers that appear to be localized have microscopic subclinical disease which is treated with breast irradiation. More recently, we have recognized that we can leave behind cancer in the axilla in anywhere from 13% to 27% of patients who are not receiving direct axillary radiation, and see failure rates of 1% or less.

In the context, then, of our current understanding of breast cancer biology, what outcomes could MRI be expected to improve, since the purpose of a test is to improve patient outcomes?

We know that MRI will not improve survival, because 30 years ago randomized trials showed us that survival was equal between breast conservation and mastectomy.

MRI has no apparent effect on reducing local recurrences either, as shown in an analysis of data on 3,180 patients published in 2014 (J Clin Oncol. 2014;32:292).

Regarding contralateral breast cancer, a 2007 study (N Engl J Med. 2007;356:1295-303) showed that among 969 women, MRI found unsuspected cancer in the contralateral breast within 1 year of diagnosis in 3.1%, a finding used to support the argument that all women with breast cancer should have an MRI. But a second study using Surveillance, Epidemiology and End Results (SEER) data on 339,790 women with 2.5 million person-years of follow-up found that the 10-year rate of contralateral cancers was 2%-3% of women with estrogen-receptor–positive tumors, and in 5%-6% of those with estrogen-receptor–negative tumors, strongly suggesting that MRI leads to detection and treatment of disease that would never become clinically evident.

Finally, I would point to evidence that MRI does not improve short-term surgical outcomes, as shown in a meta-analysis my colleagues and I conducted of two randomized controlled trials and seven cohort studies, involving a total of 3,112 patients (Ann Surg. 2013;257:249-55).

We found that after adjustment for age, having an MRI was associated with a three-fold greater chance of having a mastectomy, and MRI did not significantly reduce either the need for re-excision or unexpected conversion to mastectomy. We also performed a subanalysis of infiltrating lobular cancers, and found that there was no statistically significant benefit for MRI in these patients.

The overall rate of mastectomy was 25.5% among patients who had an MRI, vs. 18.2% for those who did not.

So to summarize: MRI finds two to three times more cancer than observed rates of local recurrence, leading to unnecessary mastectomies and does not improve short-term surgical outcomes, and there is no evidence indicating that MRI decreases local recurrence.

Monica Morrow, MD, FACS, is chief of the breast service in the department of surgery and holds the Anne Burnett Windfohr Chair of Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York.

Yes: MRI should be considered in the preoperative setting for specific clinical indications.

MRI, like any technology, has its strengths and weaknesses, with high sensitivity but low specificity. Importantly, MRI provides excellent soft tissue contrast with anatomic 3-D detail, and is not impeded by high breast density.

Admittedly, MRI only incrementally increases cancer detection rates in either the ipsilateral or contralateral breasts of all patients, and when used in the preoperative setting does not affect short-term surgical outcomes for all patients. Therefore, MRI should not be used for routine screening or routine preoperative screening.

That said, there are specific clinical situations where preoperative MRI may provide surgeons with valuable information. These include patients who have:

• Invasive lobular carcinoma.

• Neoadjuvant chemotherapy.

• Occult primaries in extremely dense breasts.

Invasive lobular carcinomas are more likely to be multi-centric, multi-focal, and/or bilateral than other breast cancer types, and they are more difficult to diagnose because they infiltrate into tissue, making it extremely difficult to determine the extent of disease. In this setting, MRI can more accurately determine tumor size than mammography. Mammography underestimates the tumor size significantly more frequently than does MRI. In addition, among women with this cancer subtype, MRI can significantly reduce the rate of excision (Breast Cancer Res Treat. 2010;119;415-22).

We know that women at risk for systemic recurrence will not be cured with surgery alone. Neoadjuvant therapies give us the opportunity to refine local therapy options, better understand the patient’s response to therapy and prognosis, and accelerate targeted drug development to improve outcomes. To accomplish all of these goals, we need a noninvasive way to assess tumors before, during, and after neoadjuvant treatment. MRI is unsurpassed for evaluating the extent of tumors, showing in larger tumors, for example, the complexity of tumor and stroma.

MRI is also a biomarker for response to therapy and has been shown to be an independent predictor of event-free survival. In addition, MRI is more accurate than either clinical exam, mammography, or ultrasound for determining residual tumor size following neoadjuvant chemotherapy (Radiology. 2012;263:663-72).

Lastly, for patients with an occult primary (by imaging) breast cancer or primary presentation of axillary node involvement, MRI has been found to have an approximately 90% sensitivity for identifying a primary tumor, and a 95% accuracy at locating the tumor in patients who undergo surgical excision. Mammography cannot distinguish a tumor mass that is dense relative to surrounding tissue. However, MRI can distinguish a tumor which is obscured by dense breast tissue because tumors are visualized on MRI by rapid contrast uptake and washout.

MRI is a catalyst for change, but you have to use it and all technology wisely: At the time of diagnosis for select patients, for screening only those patients with very breast dense tissue and very high risk for developing breast cancer, and, perhaps most importantly, for postcancer surveillance only in women at very high risk of recurrence where standard tools such as mammography are expected to have lower performance (for example, very dense breast tissue). Overuse of MRI will increase false positives, anxiety, and cost. However, used appropriately, MRI can be used to help usher in a change in practice through the evaluation of response to neoadjuvant therapy and novel therapeutic approaches to both invasive and in situ lesions.

With improvements in technology and techniques such as diffusion-weighted imaging, the value of MRI in the preoperative setting can only continue to grow. We can also expect greater performance for presurgical staging with more refined technologies for breast imaging, localization, and biopsy, but the costs have to come down. Breast-dedicated MRI technologies may address this need.

Laura Esserman, MD, is a professor of surgery and radiology at the University of California, San Francisco, and Director of the Carol Franc Buck Breast Care Center at the UCSF Mount Zion campus.

No: MRI leads to unnecessary surgeries and does not improve short-term surgical outcomes.

The key word in this debate is “routinely.” I agree that preoperative MRI may have a role in about 5% of all cases – namely in women with occult primaries and those who undergo neoadjuvant chemotherapy. But for the vast majority of patients, the 95%, I would argue that preoperative MRI has the potential to do more harm than good.

Thirty years of experience providing breast conserving therapies without MRI has taught us several important lessons:

• Selection of patients for breast-conserving therapy is not a big problem.

• The incidences of local recurrence and contralateral breast cancers have decreased over time, antedating the use of MRI.

• Surgical excision of all microscopic subclinical disease is not necessary to achieve good long-term outcomes.

In National Surgical Adjuvant Breast and Bowel Project studies from the 1990s, in the era before the use of aromatase inhibitors or HER-2 blockade, the 10-year incidence of ipsilateral breast tumor recurrence ranged from 3.5% to 6.5% in the breast cancer population at large.

In addition, the incidence of contralateral breast cancers has been declining at a rate of approximately 3% per year, thanks to the use of adjuvant systemic therapies.

We have known since the 1960s, thanks to our colleagues in pathology, that somewhere between 30% and 60% of breast cancers that appear to be localized have microscopic subclinical disease which is treated with breast irradiation. More recently, we have recognized that we can leave behind cancer in the axilla in anywhere from 13% to 27% of patients who are not receiving direct axillary radiation, and see failure rates of 1% or less.

In the context, then, of our current understanding of breast cancer biology, what outcomes could MRI be expected to improve, since the purpose of a test is to improve patient outcomes?

We know that MRI will not improve survival, because 30 years ago randomized trials showed us that survival was equal between breast conservation and mastectomy.

MRI has no apparent effect on reducing local recurrences either, as shown in an analysis of data on 3,180 patients published in 2014 (J Clin Oncol. 2014;32:292).

Regarding contralateral breast cancer, a 2007 study (N Engl J Med. 2007;356:1295-303) showed that among 969 women, MRI found unsuspected cancer in the contralateral breast within 1 year of diagnosis in 3.1%, a finding used to support the argument that all women with breast cancer should have an MRI. But a second study using Surveillance, Epidemiology and End Results (SEER) data on 339,790 women with 2.5 million person-years of follow-up found that the 10-year rate of contralateral cancers was 2%-3% of women with estrogen-receptor–positive tumors, and in 5%-6% of those with estrogen-receptor–negative tumors, strongly suggesting that MRI leads to detection and treatment of disease that would never become clinically evident.

Finally, I would point to evidence that MRI does not improve short-term surgical outcomes, as shown in a meta-analysis my colleagues and I conducted of two randomized controlled trials and seven cohort studies, involving a total of 3,112 patients (Ann Surg. 2013;257:249-55).

We found that after adjustment for age, having an MRI was associated with a three-fold greater chance of having a mastectomy, and MRI did not significantly reduce either the need for re-excision or unexpected conversion to mastectomy. We also performed a subanalysis of infiltrating lobular cancers, and found that there was no statistically significant benefit for MRI in these patients.

The overall rate of mastectomy was 25.5% among patients who had an MRI, vs. 18.2% for those who did not.

So to summarize: MRI finds two to three times more cancer than observed rates of local recurrence, leading to unnecessary mastectomies and does not improve short-term surgical outcomes, and there is no evidence indicating that MRI decreases local recurrence.

Monica Morrow, MD, FACS, is chief of the breast service in the department of surgery and holds the Anne Burnett Windfohr Chair of Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York.

A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.

Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.

To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.

“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.

To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).

For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email [email protected].

According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to [email protected]; or by submitting a report online to Medwatch.

[email protected]

On Twitter @jessnicolecraig

A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.

Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.

To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.

“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.

To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).

For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email [email protected].

According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to [email protected]; or by submitting a report online to Medwatch.

[email protected]

On Twitter @jessnicolecraig

A critical shortage of doxorubicin hydrochloride 50 mg powder for injection has been reported to the Food and Drug Administration.

Doxorubicin is approved to treat acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, gastric cancer, ovarian cancer, neuroblastoma, and other cancer types.

To increase availability, the pharmaceutical company Hospira (a Pfizer company) is coordinating with the FDA to import the drug from Ahmedabad, India, where it is manufactured by Zydus Hospira Oncology Private Ltd. at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements.

“It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved doxorubicin hydrochloride for injection, USP and the Hospira Limited’s doxorubicin hydrochloride 50 mg powder for injection,” Hospira reported in a letter to health care providers.

To place an order or to get questions answered, contact Hospira directly by calling customer care at 1-877-946-7747 (Mondays-Fridays, 7 a.m.-6 p.m. Central time).

For clinical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or email [email protected].

According to the letter, adverse events or quality problems associated with use of this product should be reported by calling Hospira Global Complaint Management by phone, 1-800-441-4100; by sending an email to [email protected]; or by submitting a report online to Medwatch.

[email protected]

On Twitter @jessnicolecraig

Genetic counseling by telephone was noninferior to in-person counseling among women at increased risk of hereditary breast and/or ovarian cancer (HBOC) for all psychosocial, decision-making, and quality-of-life measures, investigators found.

In addition, genetic testing was more common among women who received in-person counseling and women who lived in rural settings.

Gio_tto/Thinkstock

“This trial provides important evidence that telephone genetic counseling for HBOC is noninferior to in-person counseling and can be delivered as safely as in-person counseling without an adverse effect on long-term psychological, quality-of-life, and decision-making outcomes,” according to Anita Kinney, Ph.D., of the University of New Mexico, Albuquerque, and her associates (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.9557).

Investigators used the Utah Population Database and Utah Cancer Registry to identify breast and ovarian cancer survivors and their at-risk female relatives with deleterious BRCA 1/2 mutations. Of the 988 women who met study requirements, 495 were randomly assigned to receive in-person genetic counseling, and 493 women were assigned to receive genetic counseling via telephone. All patients received counseling by a certified cancer genetic counselor according to standardized national protocols. Importantly, there were no significant differences in age, race/ethnicity, marital status, education level, rural vs. urban residence, income, employment status or health care coverage between the two study arms.

At the 1-year follow-up, there was no significant difference between patients receiving in-person or telephone counseling for all psychosocial and informed decision-making outcomes which included anxiety (average brief symptom inventory scores, 2.37 vs. 2.74), cancer-specific distress (average impact of event scores, 10.06 vs. 11.19), quality-of-life for physical health (average short form health survey scores, 50.54 vs. 49.75), quality-of-life for mental health (50.51 vs. 50.74), decisional conflict (average decisional conflict score, 26.88 vs. 26.76), decisional regret (average decision regret score, 21.38 vs. 21.07), and perceived personal control (average questionnaire scores, 1.53 vs. 1.52).

Genetic testing was more common among women who received in-person counseling (37.3% vs. 27.9%; 95% confidence interval comparing difference in testing uptake, 2.2%-16.8%). Interestingly, testing was higher for rural, compared with urban residents, for both telephone and in-person counseling.

This study received funding from the National Institutes of Health, the Huntsman Cancer Foundation, the University of New Mexico Comprehensive Cancer Center, and the University of Utah. Twelve of the investigators had no disclosures to report. Two investigators reported serving in advisory roles or receiving honoraria from Myriad Genetics or In Vitae.

[email protected]

On Twitter @jessnicolecraig

Genetic counseling by telephone was noninferior to in-person counseling among women at increased risk of hereditary breast and/or ovarian cancer (HBOC) for all psychosocial, decision-making, and quality-of-life measures, investigators found.

In addition, genetic testing was more common among women who received in-person counseling and women who lived in rural settings.

Gio_tto/Thinkstock

“This trial provides important evidence that telephone genetic counseling for HBOC is noninferior to in-person counseling and can be delivered as safely as in-person counseling without an adverse effect on long-term psychological, quality-of-life, and decision-making outcomes,” according to Anita Kinney, Ph.D., of the University of New Mexico, Albuquerque, and her associates (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.9557).

Investigators used the Utah Population Database and Utah Cancer Registry to identify breast and ovarian cancer survivors and their at-risk female relatives with deleterious BRCA 1/2 mutations. Of the 988 women who met study requirements, 495 were randomly assigned to receive in-person genetic counseling, and 493 women were assigned to receive genetic counseling via telephone. All patients received counseling by a certified cancer genetic counselor according to standardized national protocols. Importantly, there were no significant differences in age, race/ethnicity, marital status, education level, rural vs. urban residence, income, employment status or health care coverage between the two study arms.

At the 1-year follow-up, there was no significant difference between patients receiving in-person or telephone counseling for all psychosocial and informed decision-making outcomes which included anxiety (average brief symptom inventory scores, 2.37 vs. 2.74), cancer-specific distress (average impact of event scores, 10.06 vs. 11.19), quality-of-life for physical health (average short form health survey scores, 50.54 vs. 49.75), quality-of-life for mental health (50.51 vs. 50.74), decisional conflict (average decisional conflict score, 26.88 vs. 26.76), decisional regret (average decision regret score, 21.38 vs. 21.07), and perceived personal control (average questionnaire scores, 1.53 vs. 1.52).

Genetic testing was more common among women who received in-person counseling (37.3% vs. 27.9%; 95% confidence interval comparing difference in testing uptake, 2.2%-16.8%). Interestingly, testing was higher for rural, compared with urban residents, for both telephone and in-person counseling.

This study received funding from the National Institutes of Health, the Huntsman Cancer Foundation, the University of New Mexico Comprehensive Cancer Center, and the University of Utah. Twelve of the investigators had no disclosures to report. Two investigators reported serving in advisory roles or receiving honoraria from Myriad Genetics or In Vitae.

[email protected]

On Twitter @jessnicolecraig

Genetic counseling by telephone was noninferior to in-person counseling among women at increased risk of hereditary breast and/or ovarian cancer (HBOC) for all psychosocial, decision-making, and quality-of-life measures, investigators found.

In addition, genetic testing was more common among women who received in-person counseling and women who lived in rural settings.

Gio_tto/Thinkstock

“This trial provides important evidence that telephone genetic counseling for HBOC is noninferior to in-person counseling and can be delivered as safely as in-person counseling without an adverse effect on long-term psychological, quality-of-life, and decision-making outcomes,” according to Anita Kinney, Ph.D., of the University of New Mexico, Albuquerque, and her associates (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2015.65.9557).

Investigators used the Utah Population Database and Utah Cancer Registry to identify breast and ovarian cancer survivors and their at-risk female relatives with deleterious BRCA 1/2 mutations. Of the 988 women who met study requirements, 495 were randomly assigned to receive in-person genetic counseling, and 493 women were assigned to receive genetic counseling via telephone. All patients received counseling by a certified cancer genetic counselor according to standardized national protocols. Importantly, there were no significant differences in age, race/ethnicity, marital status, education level, rural vs. urban residence, income, employment status or health care coverage between the two study arms.

At the 1-year follow-up, there was no significant difference between patients receiving in-person or telephone counseling for all psychosocial and informed decision-making outcomes which included anxiety (average brief symptom inventory scores, 2.37 vs. 2.74), cancer-specific distress (average impact of event scores, 10.06 vs. 11.19), quality-of-life for physical health (average short form health survey scores, 50.54 vs. 49.75), quality-of-life for mental health (50.51 vs. 50.74), decisional conflict (average decisional conflict score, 26.88 vs. 26.76), decisional regret (average decision regret score, 21.38 vs. 21.07), and perceived personal control (average questionnaire scores, 1.53 vs. 1.52).

Genetic testing was more common among women who received in-person counseling (37.3% vs. 27.9%; 95% confidence interval comparing difference in testing uptake, 2.2%-16.8%). Interestingly, testing was higher for rural, compared with urban residents, for both telephone and in-person counseling.

This study received funding from the National Institutes of Health, the Huntsman Cancer Foundation, the University of New Mexico Comprehensive Cancer Center, and the University of Utah. Twelve of the investigators had no disclosures to report. Two investigators reported serving in advisory roles or receiving honoraria from Myriad Genetics or In Vitae.

[email protected]

On Twitter @jessnicolecraig

CHICAGO – Combining two immunotherapies, one inhibiting immune suppression and the other stimulating immune activation, is well tolerated and shows activity for a variety of solid tumor types, according to a phase I trial presented at the annual meeting of the American Association of Clinical Oncology.

Investigators enrolled 51 patients with locally advanced or metastatic solid tumors of any type after progression on standard therapy to a phase Ib dose-escalation study using atezolizumab, a monoclonal antibody checkpoint inhibitor that targets PD-L1, in combination with MOXR0916 (MOXR), an agonist IgG1 monoclonal antibody targeting OX40, a costimulatory receptor. Atezolizumab received Food and Drug Administration approval in May 2016 for use in certain patients with urothelial carcinoma. There were 28 patients in a dose-escalation cohort of the study and 23 in a serial biopsy cohort. The dose of the drug combination was started at 12 mg and escalated to understand pharmacodynamic changes in the tumors.

“The pharmacokinetics of both MOXR0916 and atezolizumab were similar to their single-agent data, suggesting no interaction,” reported Dr. Jeffrey Infante of the Sarah Cannon Research Institute in Nashville, Tenn.

The drug combination was well tolerated through the entire escalation range of MOXR. There were no dose-limiting toxicities, and no maximal tolerated dose was reached. There were also no drug-related deaths or grade 4 toxicities or drug-related treatment discontinuations. One case of grade 3 pneumonitis, successfully managed with methylprednisolone and antibiotics, occurred at the MOXR 40-mg dose on cycle 4 of treatment in a patient with non–small-cell lung cancer, he said.

About half the patients (53%) experienced any form of adverse event on the drug combination, and only 8% were grade 2 or 3. There were very few adverse events of any one type, and they did not appear to cluster among patients on the higher MOXR doses. The most prevalent adverse events were nausea, fever, fatigue, and rash, and each was in the 8%-14% range and almost always grade 1.

Many patients showed efficacy of the regimens out to 6-7 cycles regardless of tumor type, and 8 of the 51 patients were still receiving the therapy past cycle 7 with partial responses.

The stimulatory molecule OX40 is not normally expressed on T cells, but it is expressed when antigen interacts with the T-cell receptor, and it can then interact with its ligand, OX40L. The result is production of inflammatory cytokines such as gamma-interferon, activation and survival of effector T cells, and production of memory T cells. At the same time, OX40 activity blocks the suppressive function of regulatory T cells.

“So a molecule that can be a cancer therapeutic such as an OX40 agonist has dual mechanisms of action,” Dr. Infante said. “It can costimulate effector T cells and at the same time inhibit regulatory T cells. Furthermore, there is a reduced risk of toxicity, potentially, as its activity is linked to antigen recognition.”

There is good rationale for using an OX40 agonist such as MOXR, either for its immune stimulatory function or to deactivate immune suppression by regulatory T cells, or both, said discussant Dr. Jedd Wolchok, chief, melanoma and immunotherapeutics service, Memorial Sloan-Kettering Cancer Center, New York. Dr. Infante’s dose-escalation study was “very nicely designed and showed quite good safety,” Dr. Wolchok said, though one thing he would have liked to have seen was a quantification of regulatory T cells in tumor biopsies.

“This [study] is very important considering that this is an agonist antibody, and the agonist agents need to be dosed very deliberatively, as was done here, to ensure safety of patients,” Dr. Wolchok said, adding that further research needs to target “optimal combinatorial partners” and explore other mechanistic biomarkers.

MOXR was given in this trial at escalating doses on a 3+3 design (0.8-1,200 mg) on the same day as atezolizumab 1,200 mg IV once every 3 weeks with a 21-day window for assessment of MOXR dose-limiting toxicities. MOXR doses of 300 mg maintained trough concentrations sufficient to saturate OX40 receptors. An expansion regimen using 300 mg MOXR with atezolizumab 1,200 mg every 3 weeks is underway and will assess efficacy in the treatment of melanoma, renal cell carcinoma, non–small-cell lung cancer, urothelial carcinoma, and triple-negative breast cancer.

The study was sponsored by Roche. Dr. Infante reported having no relevant financial disclosures. Dr. Wolchok owns stock in Potenza Therapeutics and Vesuvius Pharmaceuticals, has received travel expenses and/or has an advisory role with several other companies, and is a coinventor on an issued patent for DNA vaccines for the treatment of cancer in companion animals.

CHICAGO – Combining two immunotherapies, one inhibiting immune suppression and the other stimulating immune activation, is well tolerated and shows activity for a variety of solid tumor types, according to a phase I trial presented at the annual meeting of the American Association of Clinical Oncology.

Investigators enrolled 51 patients with locally advanced or metastatic solid tumors of any type after progression on standard therapy to a phase Ib dose-escalation study using atezolizumab, a monoclonal antibody checkpoint inhibitor that targets PD-L1, in combination with MOXR0916 (MOXR), an agonist IgG1 monoclonal antibody targeting OX40, a costimulatory receptor. Atezolizumab received Food and Drug Administration approval in May 2016 for use in certain patients with urothelial carcinoma. There were 28 patients in a dose-escalation cohort of the study and 23 in a serial biopsy cohort. The dose of the drug combination was started at 12 mg and escalated to understand pharmacodynamic changes in the tumors.

“The pharmacokinetics of both MOXR0916 and atezolizumab were similar to their single-agent data, suggesting no interaction,” reported Dr. Jeffrey Infante of the Sarah Cannon Research Institute in Nashville, Tenn.

The drug combination was well tolerated through the entire escalation range of MOXR. There were no dose-limiting toxicities, and no maximal tolerated dose was reached. There were also no drug-related deaths or grade 4 toxicities or drug-related treatment discontinuations. One case of grade 3 pneumonitis, successfully managed with methylprednisolone and antibiotics, occurred at the MOXR 40-mg dose on cycle 4 of treatment in a patient with non–small-cell lung cancer, he said.

About half the patients (53%) experienced any form of adverse event on the drug combination, and only 8% were grade 2 or 3. There were very few adverse events of any one type, and they did not appear to cluster among patients on the higher MOXR doses. The most prevalent adverse events were nausea, fever, fatigue, and rash, and each was in the 8%-14% range and almost always grade 1.

Many patients showed efficacy of the regimens out to 6-7 cycles regardless of tumor type, and 8 of the 51 patients were still receiving the therapy past cycle 7 with partial responses.

The stimulatory molecule OX40 is not normally expressed on T cells, but it is expressed when antigen interacts with the T-cell receptor, and it can then interact with its ligand, OX40L. The result is production of inflammatory cytokines such as gamma-interferon, activation and survival of effector T cells, and production of memory T cells. At the same time, OX40 activity blocks the suppressive function of regulatory T cells.

“So a molecule that can be a cancer therapeutic such as an OX40 agonist has dual mechanisms of action,” Dr. Infante said. “It can costimulate effector T cells and at the same time inhibit regulatory T cells. Furthermore, there is a reduced risk of toxicity, potentially, as its activity is linked to antigen recognition.”

There is good rationale for using an OX40 agonist such as MOXR, either for its immune stimulatory function or to deactivate immune suppression by regulatory T cells, or both, said discussant Dr. Jedd Wolchok, chief, melanoma and immunotherapeutics service, Memorial Sloan-Kettering Cancer Center, New York. Dr. Infante’s dose-escalation study was “very nicely designed and showed quite good safety,” Dr. Wolchok said, though one thing he would have liked to have seen was a quantification of regulatory T cells in tumor biopsies.

“This [study] is very important considering that this is an agonist antibody, and the agonist agents need to be dosed very deliberatively, as was done here, to ensure safety of patients,” Dr. Wolchok said, adding that further research needs to target “optimal combinatorial partners” and explore other mechanistic biomarkers.

MOXR was given in this trial at escalating doses on a 3+3 design (0.8-1,200 mg) on the same day as atezolizumab 1,200 mg IV once every 3 weeks with a 21-day window for assessment of MOXR dose-limiting toxicities. MOXR doses of 300 mg maintained trough concentrations sufficient to saturate OX40 receptors. An expansion regimen using 300 mg MOXR with atezolizumab 1,200 mg every 3 weeks is underway and will assess efficacy in the treatment of melanoma, renal cell carcinoma, non–small-cell lung cancer, urothelial carcinoma, and triple-negative breast cancer.

The study was sponsored by Roche. Dr. Infante reported having no relevant financial disclosures. Dr. Wolchok owns stock in Potenza Therapeutics and Vesuvius Pharmaceuticals, has received travel expenses and/or has an advisory role with several other companies, and is a coinventor on an issued patent for DNA vaccines for the treatment of cancer in companion animals.

CHICAGO – Combining two immunotherapies, one inhibiting immune suppression and the other stimulating immune activation, is well tolerated and shows activity for a variety of solid tumor types, according to a phase I trial presented at the annual meeting of the American Association of Clinical Oncology.

Investigators enrolled 51 patients with locally advanced or metastatic solid tumors of any type after progression on standard therapy to a phase Ib dose-escalation study using atezolizumab, a monoclonal antibody checkpoint inhibitor that targets PD-L1, in combination with MOXR0916 (MOXR), an agonist IgG1 monoclonal antibody targeting OX40, a costimulatory receptor. Atezolizumab received Food and Drug Administration approval in May 2016 for use in certain patients with urothelial carcinoma. There were 28 patients in a dose-escalation cohort of the study and 23 in a serial biopsy cohort. The dose of the drug combination was started at 12 mg and escalated to understand pharmacodynamic changes in the tumors.

“The pharmacokinetics of both MOXR0916 and atezolizumab were similar to their single-agent data, suggesting no interaction,” reported Dr. Jeffrey Infante of the Sarah Cannon Research Institute in Nashville, Tenn.

The drug combination was well tolerated through the entire escalation range of MOXR. There were no dose-limiting toxicities, and no maximal tolerated dose was reached. There were also no drug-related deaths or grade 4 toxicities or drug-related treatment discontinuations. One case of grade 3 pneumonitis, successfully managed with methylprednisolone and antibiotics, occurred at the MOXR 40-mg dose on cycle 4 of treatment in a patient with non–small-cell lung cancer, he said.

About half the patients (53%) experienced any form of adverse event on the drug combination, and only 8% were grade 2 or 3. There were very few adverse events of any one type, and they did not appear to cluster among patients on the higher MOXR doses. The most prevalent adverse events were nausea, fever, fatigue, and rash, and each was in the 8%-14% range and almost always grade 1.

Many patients showed efficacy of the regimens out to 6-7 cycles regardless of tumor type, and 8 of the 51 patients were still receiving the therapy past cycle 7 with partial responses.

The stimulatory molecule OX40 is not normally expressed on T cells, but it is expressed when antigen interacts with the T-cell receptor, and it can then interact with its ligand, OX40L. The result is production of inflammatory cytokines such as gamma-interferon, activation and survival of effector T cells, and production of memory T cells. At the same time, OX40 activity blocks the suppressive function of regulatory T cells.

“So a molecule that can be a cancer therapeutic such as an OX40 agonist has dual mechanisms of action,” Dr. Infante said. “It can costimulate effector T cells and at the same time inhibit regulatory T cells. Furthermore, there is a reduced risk of toxicity, potentially, as its activity is linked to antigen recognition.”

There is good rationale for using an OX40 agonist such as MOXR, either for its immune stimulatory function or to deactivate immune suppression by regulatory T cells, or both, said discussant Dr. Jedd Wolchok, chief, melanoma and immunotherapeutics service, Memorial Sloan-Kettering Cancer Center, New York. Dr. Infante’s dose-escalation study was “very nicely designed and showed quite good safety,” Dr. Wolchok said, though one thing he would have liked to have seen was a quantification of regulatory T cells in tumor biopsies.

“This [study] is very important considering that this is an agonist antibody, and the agonist agents need to be dosed very deliberatively, as was done here, to ensure safety of patients,” Dr. Wolchok said, adding that further research needs to target “optimal combinatorial partners” and explore other mechanistic biomarkers.

MOXR was given in this trial at escalating doses on a 3+3 design (0.8-1,200 mg) on the same day as atezolizumab 1,200 mg IV once every 3 weeks with a 21-day window for assessment of MOXR dose-limiting toxicities. MOXR doses of 300 mg maintained trough concentrations sufficient to saturate OX40 receptors. An expansion regimen using 300 mg MOXR with atezolizumab 1,200 mg every 3 weeks is underway and will assess efficacy in the treatment of melanoma, renal cell carcinoma, non–small-cell lung cancer, urothelial carcinoma, and triple-negative breast cancer.

The study was sponsored by Roche. Dr. Infante reported having no relevant financial disclosures. Dr. Wolchok owns stock in Potenza Therapeutics and Vesuvius Pharmaceuticals, has received travel expenses and/or has an advisory role with several other companies, and is a coinventor on an issued patent for DNA vaccines for the treatment of cancer in companion animals.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Do anthracyclines still have a role in treating breast cancer? What are the implications for resistance of extending adjuvant aromatase inhibitors to 10 years or beyond? How best to treat women with metastatic hormone receptor–positive breast cancer, in light of findings on CDK 4/6 and mTOR inhibitors? Does sequence matter? In the case of HER2-positive disease, can a trastuzumab biosimilar be as effective as trastuzumab? And does a regimen with TDM-1 do more than reduce toxicity?

Dr. William A. Gradishar and Dr. Hope S. Rugo reflect on these questions and more in a video roundtable at the annual meeting of the American Society of Clinical Oncology.

Dr. William A. Gradishar is the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago. He had no disclosures to report. Dr. Hope S. Rugo is professor of medicine at the University of California, San Francisco. She disclosed she is on the Speakers’ Bureau for Genomic Health and receives research funding (institutional) from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, and Merck.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – Do anthracyclines still have a role in treating breast cancer? What are the implications for resistance of extending adjuvant aromatase inhibitors to 10 years or beyond? How best to treat women with metastatic hormone receptor–positive breast cancer, in light of findings on CDK 4/6 and mTOR inhibitors? Does sequence matter? In the case of HER2-positive disease, can a trastuzumab biosimilar be as effective as trastuzumab? And does a regimen with TDM-1 do more than reduce toxicity?

Dr. William A. Gradishar and Dr. Hope S. Rugo reflect on these questions and more in a video roundtable at the annual meeting of the American Society of Clinical Oncology.

Dr. William A. Gradishar is the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago. He had no disclosures to report. Dr. Hope S. Rugo is professor of medicine at the University of California, San Francisco. She disclosed she is on the Speakers’ Bureau for Genomic Health and receives research funding (institutional) from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, and Merck.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – Do anthracyclines still have a role in treating breast cancer? What are the implications for resistance of extending adjuvant aromatase inhibitors to 10 years or beyond? How best to treat women with metastatic hormone receptor–positive breast cancer, in light of findings on CDK 4/6 and mTOR inhibitors? Does sequence matter? In the case of HER2-positive disease, can a trastuzumab biosimilar be as effective as trastuzumab? And does a regimen with TDM-1 do more than reduce toxicity?

Dr. William A. Gradishar and Dr. Hope S. Rugo reflect on these questions and more in a video roundtable at the annual meeting of the American Society of Clinical Oncology.

Dr. William A. Gradishar is the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago. He had no disclosures to report. Dr. Hope S. Rugo is professor of medicine at the University of California, San Francisco. She disclosed she is on the Speakers’ Bureau for Genomic Health and receives research funding (institutional) from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, and Merck.

[email protected]

On Twitter @NikolaidesLaura

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]