Breast Cancer

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

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“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

sdominick/iStock/Getty Images

“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

sdominick/iStock/Getty Images

“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

It’s a toss-up: For patients with early, HER2-positive breast cancer, subcutaneous trastuzumab is comparable in efficacy and safety with intravenous trastuzumab, final results of the phase 3, randomized HannaH trial indicate.

The 6-year event-free survival (EFS) and overall survival (OS) rates were identical for patients randomized either to subcutaneously or intravenously delivered trastuzumab (Herceptin and biosimilars); adverse events rates also were similar, reported Christian Jackisch, MD, PhD, from Sana Klinikum Offenbach, Germany, and his associates.

“Event-free survival and OS results after 6 years of follow-up continue to support the noninferiority of subcutaneous trastuzumab to intravenous trastuzumab observed in the primary analysis. Results for EFS were consistent with those observed in the Neoadjuvant Herceptin [NOAH] trial of intravenous trastuzumab,” the investigators wrote in JAMA Oncology.

The HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial was designed to show whether subcutaneous trastuzumab was noninferior to intravenous trastuzumab for patients with HER2 (ERBB2)-positive early breast cancer.

Patients received four cycles of neoadjuvant docetaxel, followed by four cycles of combination chemotherapy with fluorouracil, epirubicin, and cyclophosphamide, plus either subcutaneous trastuzumab 600 mg delivered over 5 minutes or IV trastuzumab at a loading dose of 8 mg/kg and maintenance dose of 6 mg/kg every 3 weeks. Patients received an additional 10 cycles of trastuzumab post surgery.

The coprimary endpoints were pathologic complete response, defined as absence of invasive neoplastic cells in the breast (remaining ductal carcinoma in situ was accepted) and serum trough concentration predose on dose cycle 8.

The primary analysis, published in 2012, showed that the subcutaneous formulation has pharmacokinetic, efficacy and safety profiles comparable with those of standard intravenous administration. Subsequent analyses showed similar 3-year EFS rates and safety profiles, Dr. Jackisch and colleagues noted.

The current, final analysis was conducted after a median follow-up of 5.9 years in an intention-to-treat population within the subcutaneous group (294 women), and 6.0 years in the intravenous group (297 women).

The 6-year EFS rate was 65% in each group, and the OS rate was 84% in each group. In both trial arms, 6-year EFS and OS rates were higher for patients with complete pathologic responses than for patients with residual disease.

Adverse events of any grade were reported in 97.6% in the subcutaneous group and 94.6% in the intravenous group. Grade 3 or greater adverse events occurred in 53.2% versus 53.7%, cardiac adverse events in 14.8% versus 14.1%, and serious adverse events in 21.9% versus 15.1%, respectively.

The HannaH trial was sponsored by Hoffman-La Roche. Dr. Jackisch and several coauthors reported receiving grants and personal fees from Hoffmann-La Roche.

SOURCE: Jackisch C et al. JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339.

It’s a toss-up: For patients with early, HER2-positive breast cancer, subcutaneous trastuzumab is comparable in efficacy and safety with intravenous trastuzumab, final results of the phase 3, randomized HannaH trial indicate.

The 6-year event-free survival (EFS) and overall survival (OS) rates were identical for patients randomized either to subcutaneously or intravenously delivered trastuzumab (Herceptin and biosimilars); adverse events rates also were similar, reported Christian Jackisch, MD, PhD, from Sana Klinikum Offenbach, Germany, and his associates.

“Event-free survival and OS results after 6 years of follow-up continue to support the noninferiority of subcutaneous trastuzumab to intravenous trastuzumab observed in the primary analysis. Results for EFS were consistent with those observed in the Neoadjuvant Herceptin [NOAH] trial of intravenous trastuzumab,” the investigators wrote in JAMA Oncology.

The HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial was designed to show whether subcutaneous trastuzumab was noninferior to intravenous trastuzumab for patients with HER2 (ERBB2)-positive early breast cancer.

Patients received four cycles of neoadjuvant docetaxel, followed by four cycles of combination chemotherapy with fluorouracil, epirubicin, and cyclophosphamide, plus either subcutaneous trastuzumab 600 mg delivered over 5 minutes or IV trastuzumab at a loading dose of 8 mg/kg and maintenance dose of 6 mg/kg every 3 weeks. Patients received an additional 10 cycles of trastuzumab post surgery.

The coprimary endpoints were pathologic complete response, defined as absence of invasive neoplastic cells in the breast (remaining ductal carcinoma in situ was accepted) and serum trough concentration predose on dose cycle 8.

The primary analysis, published in 2012, showed that the subcutaneous formulation has pharmacokinetic, efficacy and safety profiles comparable with those of standard intravenous administration. Subsequent analyses showed similar 3-year EFS rates and safety profiles, Dr. Jackisch and colleagues noted.

The current, final analysis was conducted after a median follow-up of 5.9 years in an intention-to-treat population within the subcutaneous group (294 women), and 6.0 years in the intravenous group (297 women).

The 6-year EFS rate was 65% in each group, and the OS rate was 84% in each group. In both trial arms, 6-year EFS and OS rates were higher for patients with complete pathologic responses than for patients with residual disease.

Adverse events of any grade were reported in 97.6% in the subcutaneous group and 94.6% in the intravenous group. Grade 3 or greater adverse events occurred in 53.2% versus 53.7%, cardiac adverse events in 14.8% versus 14.1%, and serious adverse events in 21.9% versus 15.1%, respectively.

The HannaH trial was sponsored by Hoffman-La Roche. Dr. Jackisch and several coauthors reported receiving grants and personal fees from Hoffmann-La Roche.

SOURCE: Jackisch C et al. JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339.

It’s a toss-up: For patients with early, HER2-positive breast cancer, subcutaneous trastuzumab is comparable in efficacy and safety with intravenous trastuzumab, final results of the phase 3, randomized HannaH trial indicate.

The 6-year event-free survival (EFS) and overall survival (OS) rates were identical for patients randomized either to subcutaneously or intravenously delivered trastuzumab (Herceptin and biosimilars); adverse events rates also were similar, reported Christian Jackisch, MD, PhD, from Sana Klinikum Offenbach, Germany, and his associates.

“Event-free survival and OS results after 6 years of follow-up continue to support the noninferiority of subcutaneous trastuzumab to intravenous trastuzumab observed in the primary analysis. Results for EFS were consistent with those observed in the Neoadjuvant Herceptin [NOAH] trial of intravenous trastuzumab,” the investigators wrote in JAMA Oncology.

The HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial was designed to show whether subcutaneous trastuzumab was noninferior to intravenous trastuzumab for patients with HER2 (ERBB2)-positive early breast cancer.

Patients received four cycles of neoadjuvant docetaxel, followed by four cycles of combination chemotherapy with fluorouracil, epirubicin, and cyclophosphamide, plus either subcutaneous trastuzumab 600 mg delivered over 5 minutes or IV trastuzumab at a loading dose of 8 mg/kg and maintenance dose of 6 mg/kg every 3 weeks. Patients received an additional 10 cycles of trastuzumab post surgery.

The coprimary endpoints were pathologic complete response, defined as absence of invasive neoplastic cells in the breast (remaining ductal carcinoma in situ was accepted) and serum trough concentration predose on dose cycle 8.

The primary analysis, published in 2012, showed that the subcutaneous formulation has pharmacokinetic, efficacy and safety profiles comparable with those of standard intravenous administration. Subsequent analyses showed similar 3-year EFS rates and safety profiles, Dr. Jackisch and colleagues noted.

The current, final analysis was conducted after a median follow-up of 5.9 years in an intention-to-treat population within the subcutaneous group (294 women), and 6.0 years in the intravenous group (297 women).

The 6-year EFS rate was 65% in each group, and the OS rate was 84% in each group. In both trial arms, 6-year EFS and OS rates were higher for patients with complete pathologic responses than for patients with residual disease.

Adverse events of any grade were reported in 97.6% in the subcutaneous group and 94.6% in the intravenous group. Grade 3 or greater adverse events occurred in 53.2% versus 53.7%, cardiac adverse events in 14.8% versus 14.1%, and serious adverse events in 21.9% versus 15.1%, respectively.

The HannaH trial was sponsored by Hoffman-La Roche. Dr. Jackisch and several coauthors reported receiving grants and personal fees from Hoffmann-La Roche.

SOURCE: Jackisch C et al. JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339.

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

[email protected]

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

[email protected]

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

Clinicians should offer biennial mammography to screen for breast cancer in asymptomatic average-risk women aged 50-74 years and should abandon clinical breast examinations (CBE) for screening in such women of any age, according to a new guideline from the American College of Physicians.

Catherine Yeulet/Thinkstock

Further, clinicians should discuss whether to screen with mammography in average-risk women aged 40-49 years and consider potential harms and benefits, as well as patient preferences. Providers should discontinue screening average-risk women at age 75 years and women with a life expectancy of 10 years or less, Amir Qaseem, MD, PhD, of the ACP and colleagues wrote on behalf of the ACP Clinical Guidelines Committee.

The ACP guidance also addresses the varying recommendations from other organizations on the age at which to start and stop screening and on screening intervals, noting that “areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals,” and stresses the importance of patient input.

“Women should be informed participants in personalized decisions about breast cancer screening,” the authors wrote, adding that those under age 50 years without a clear preference for screening should not be screened.

However, the evidence shows that most average-risk women with no symptoms will benefit from mammography every other year beginning at age 50 years, they said.

The statement, published online April 8 in the Annals of Internal Medicine, was derived from a review of seven existing English-language breast cancer screening guidelines and the evidence cited in those guidelines. It’s intended to be a resource for all clinicians.

It differs from the 2017 American College of Obstetricians and Gynecologists (ACOG) guidelines in that ACOG recommends CBE and does not address screening in those with a life expectancy of less than 10 years. It also differs from the 2016 U.S. Preventive Services Task Force (USPSTF) guidelines, which make no recommendation on CBE and also do not address screening in those with a life expectancy of less than 10 years.

Other guidelines, such as those from the American College of Radiology, American Cancer Society (ACS), the Canadian Task Force on Preventive Health Care, and the National Comprehensive Cancer Network, recommend CBE, and the World Health Organization guidelines recommend CBE in low resource settings.

“Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography,” the ACP guideline authors wrote. “The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results.”

The guidance, which does not apply to patients with prior abnormal screening results or those at higher breast cancer risk, also includes an evidence-driven “talking points with patients” section based on frequently asked questions.

An important goal of the ACP Clinical Guidelines Committee in developing the guidance is to reduce overdiagnosis and overtreatment, which affects about 20% of women diagnosed over a 10-year period.

The committee reviewed all national guidelines published in English between January 1, 2013, and November 15, 2017, in the National Guideline Clearinghouse or Guidelines International Network library, and it also selected other guidelines commonly used in clinical practice. The committee evaluated the quality of each by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Alex Krist, MD, the USPSTF vice-chairperson, offered support for the “shift toward shared decision making that is emerging” and added it’s “part of a larger movement toward empowering people with information not only about the potential benefits but also the potential harms of screening tests.”

“In its 2016 recommendation, the Task Force found that the value of mammography increases with age, with women ages 50-74 benefiting most from screening. For women in their 40s, the Task Force also found that mammography screening every two years can be effective,” he told this publication. “We recommend that the decision to start screening should be an individual one, taking into account a woman’s health history, preferences, and how she values the different potential benefits and harms.”

Dr. Krist further noted that the USPSTF, ACP, and many others “have all affirmed that mammography is an important tool to reduce breast cancer mortality and that the benefits of mammography increase with age.”

Likewise, Robert Smith, PhD, vice president of cancer screening for the ACS, noted that the ACP guidance generally aligns with ACS and USPSTF guidelines because all “support informed decision making starting at age 40, and screening every two years starting at age 50 (USPSTF) or 55 (ACS).”

“The fact that all guidelines are not totally in sync is not unexpected. ... The most important thing to recognize is that all of these guidelines stress that regular mammography plays an important role in breast cancer early detection, and women should be aware of its benefits and limitations, and also remain vigilant and report any breast changes,” he said.

The guidance authors reported having no conflicts of interest.

[email protected]

SOURCE: Qaseem A et al., Ann Intern Med. 2019. doi: 10.7326/M18-2147.

The Food and Drug Administration has expanded the indication of palbociclib (Ibrance) in combination with specific endocrine therapies for hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer in men.

Approval was based on postmarketing reports and electronic health records showing that the safety profile for men is consistent with that of women, the FDA said in a statement.

Less than 1% of all cases of breast cancer occur in men, but in the majority of those cases the tumors do express hormone receptors. Men are more likely to be diagnosed at a more advanced stage of disease. “According to the current clinical practice standards, male patients with breast cancer are treated similarly to women with breast cancer,” the FDA said.

The kinase inhibitor palbociclib was initially approved in 2015, in combination with an aromatase inhibitor, for postmenopausal women as first-line treatment of advanced disease.

The most common side effects in patients taking palbociclib are infections, leukopenia, fatigue, nausea, stomatitis, anemia, hair loss, diarrhea, and thrombocytopenia.

Because of the potential for genotoxicity, the FDA advised health care providers to tell male patients with female partners of reproductive potential to use effective contraception during treatment with palbociclib and for 3 months after the last dose.

 

The Food and Drug Administration has expanded the indication of palbociclib (Ibrance) in combination with specific endocrine therapies for hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer in men.

Approval was based on postmarketing reports and electronic health records showing that the safety profile for men is consistent with that of women, the FDA said in a statement.

Less than 1% of all cases of breast cancer occur in men, but in the majority of those cases the tumors do express hormone receptors. Men are more likely to be diagnosed at a more advanced stage of disease. “According to the current clinical practice standards, male patients with breast cancer are treated similarly to women with breast cancer,” the FDA said.

The kinase inhibitor palbociclib was initially approved in 2015, in combination with an aromatase inhibitor, for postmenopausal women as first-line treatment of advanced disease.

The most common side effects in patients taking palbociclib are infections, leukopenia, fatigue, nausea, stomatitis, anemia, hair loss, diarrhea, and thrombocytopenia.

Because of the potential for genotoxicity, the FDA advised health care providers to tell male patients with female partners of reproductive potential to use effective contraception during treatment with palbociclib and for 3 months after the last dose.

 

The Food and Drug Administration has expanded the indication of palbociclib (Ibrance) in combination with specific endocrine therapies for hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer in men.

Approval was based on postmarketing reports and electronic health records showing that the safety profile for men is consistent with that of women, the FDA said in a statement.

Less than 1% of all cases of breast cancer occur in men, but in the majority of those cases the tumors do express hormone receptors. Men are more likely to be diagnosed at a more advanced stage of disease. “According to the current clinical practice standards, male patients with breast cancer are treated similarly to women with breast cancer,” the FDA said.

The kinase inhibitor palbociclib was initially approved in 2015, in combination with an aromatase inhibitor, for postmenopausal women as first-line treatment of advanced disease.

The most common side effects in patients taking palbociclib are infections, leukopenia, fatigue, nausea, stomatitis, anemia, hair loss, diarrhea, and thrombocytopenia.

Because of the potential for genotoxicity, the FDA advised health care providers to tell male patients with female partners of reproductive potential to use effective contraception during treatment with palbociclib and for 3 months after the last dose.

 

Proposed changes to federal mammography regulations aim to provide more information for doctors and patients, as well as standardize patient information on breast density’s impact on screening.

The Food and Drug Administration posted a new proposed rule online March 27 that would “expand the information mammography facilities must provide to patients and health care professionals, allowing for more informed medical decision making,” the agency said in a statement. “It would also modernize mammography quality standards and better position the FDA to enforce regulations that apply to the safety and quality of mammography services.”

Key among the proposed changes is the addition of breast density information to the summary letter provided to patients and to the medical report provided to referring health care professionals.

“The FDA is proposing specific language that would explain how breast density can influence the accuracy of mammography and would recommend patients with dense breasts talk to their health care provider about high breast density and how it relates to breast cancer risk and their individual situation,” the agency said in a statement.

Laurie Margolies, MD, section chief of breast imaging at Mount Sinai Health System in New York, said the regulations would bring some uniformity to the communication process.

“It builds on the experience of the 37 states and the District of Columbia, all of whom have passed dense breast notification laws, and can serve to unify those disparate regulations into one that would be uniform throughout the country to give one clear message to women and health care providers,” Dr. Margolies said in an interview.

She noted that dense breasts are very common and communicating issues that are related to them, including the potential need for supplemental screening, are important.

“Almost half of American women have dense breasts and why that is significant is because the dense breast issue not only increases one’s risk of getting breast cancer, but it also can hide small breast cancers on the mammogram,” she said.

If you take 1,000 women with dense breasts and then do a breast ultrasound as a supplemental screening measure, “you will find three more small node-negative breast cancers that would not have come to light if you didn’t do the extra supplemental screening,” underscoring the importance of communicating dense breast information, she continued.

FDA also is seeking to enhance information provided to health care professionals by codifying three additional categories for mammogram assessments, including the addition of the “known biopsy proven malignancy” category, which the agency says would help identify which scans were being used to evaluate treatment of already diagnosed cancers.

Both patients and health care professionals would receive more detailed information about the mammography facility under the proposed rule.

FDA is proposing modernization of quality standards to help the agency enforce regulations, including giving the agency the authority to notify patients and health care professionals directly if a mammography facility does not meet quality standards and that a reevaluation or repeat of the exam at a different facility may be needed. The proposed amendments also include requiring that only digital accessory components specifically FDA approved or cleared for mammography be used or that facilities use components that otherwise meet the requirements, and stronger record-keeping requirements.

Dr. Margolies did note one potential deficiency in the proposed rule – the lack of any information on health insurance coverage of supplemental screening for women with dense breasts, though she noted this may not fall under the FDA’s authority.

“It would do the most good if everybody could get the supplemental screening without regards to their ability to pay for it out of pocket,” she said.

The proposal amends regulations issued under the Mammography Quality Standards Act of 1992, which gives FDA oversight authority over mammography facilities, including accreditation, certification, annual inspection, and enforcement of standards.

Comments on the proposal are due 90 days after the proposed rule is published in the Federal Register, which is scheduled for March 28.

[email protected]

Proposed changes to federal mammography regulations aim to provide more information for doctors and patients, as well as standardize patient information on breast density’s impact on screening.

The Food and Drug Administration posted a new proposed rule online March 27 that would “expand the information mammography facilities must provide to patients and health care professionals, allowing for more informed medical decision making,” the agency said in a statement. “It would also modernize mammography quality standards and better position the FDA to enforce regulations that apply to the safety and quality of mammography services.”

Key among the proposed changes is the addition of breast density information to the summary letter provided to patients and to the medical report provided to referring health care professionals.

“The FDA is proposing specific language that would explain how breast density can influence the accuracy of mammography and would recommend patients with dense breasts talk to their health care provider about high breast density and how it relates to breast cancer risk and their individual situation,” the agency said in a statement.

Laurie Margolies, MD, section chief of breast imaging at Mount Sinai Health System in New York, said the regulations would bring some uniformity to the communication process.

“It builds on the experience of the 37 states and the District of Columbia, all of whom have passed dense breast notification laws, and can serve to unify those disparate regulations into one that would be uniform throughout the country to give one clear message to women and health care providers,” Dr. Margolies said in an interview.

She noted that dense breasts are very common and communicating issues that are related to them, including the potential need for supplemental screening, are important.

“Almost half of American women have dense breasts and why that is significant is because the dense breast issue not only increases one’s risk of getting breast cancer, but it also can hide small breast cancers on the mammogram,” she said.

If you take 1,000 women with dense breasts and then do a breast ultrasound as a supplemental screening measure, “you will find three more small node-negative breast cancers that would not have come to light if you didn’t do the extra supplemental screening,” underscoring the importance of communicating dense breast information, she continued.

FDA also is seeking to enhance information provided to health care professionals by codifying three additional categories for mammogram assessments, including the addition of the “known biopsy proven malignancy” category, which the agency says would help identify which scans were being used to evaluate treatment of already diagnosed cancers.

Both patients and health care professionals would receive more detailed information about the mammography facility under the proposed rule.

FDA is proposing modernization of quality standards to help the agency enforce regulations, including giving the agency the authority to notify patients and health care professionals directly if a mammography facility does not meet quality standards and that a reevaluation or repeat of the exam at a different facility may be needed. The proposed amendments also include requiring that only digital accessory components specifically FDA approved or cleared for mammography be used or that facilities use components that otherwise meet the requirements, and stronger record-keeping requirements.

Dr. Margolies did note one potential deficiency in the proposed rule – the lack of any information on health insurance coverage of supplemental screening for women with dense breasts, though she noted this may not fall under the FDA’s authority.

“It would do the most good if everybody could get the supplemental screening without regards to their ability to pay for it out of pocket,” she said.

The proposal amends regulations issued under the Mammography Quality Standards Act of 1992, which gives FDA oversight authority over mammography facilities, including accreditation, certification, annual inspection, and enforcement of standards.

Comments on the proposal are due 90 days after the proposed rule is published in the Federal Register, which is scheduled for March 28.

[email protected]

Proposed changes to federal mammography regulations aim to provide more information for doctors and patients, as well as standardize patient information on breast density’s impact on screening.

The Food and Drug Administration posted a new proposed rule online March 27 that would “expand the information mammography facilities must provide to patients and health care professionals, allowing for more informed medical decision making,” the agency said in a statement. “It would also modernize mammography quality standards and better position the FDA to enforce regulations that apply to the safety and quality of mammography services.”

Key among the proposed changes is the addition of breast density information to the summary letter provided to patients and to the medical report provided to referring health care professionals.

“The FDA is proposing specific language that would explain how breast density can influence the accuracy of mammography and would recommend patients with dense breasts talk to their health care provider about high breast density and how it relates to breast cancer risk and their individual situation,” the agency said in a statement.

Laurie Margolies, MD, section chief of breast imaging at Mount Sinai Health System in New York, said the regulations would bring some uniformity to the communication process.

“It builds on the experience of the 37 states and the District of Columbia, all of whom have passed dense breast notification laws, and can serve to unify those disparate regulations into one that would be uniform throughout the country to give one clear message to women and health care providers,” Dr. Margolies said in an interview.

She noted that dense breasts are very common and communicating issues that are related to them, including the potential need for supplemental screening, are important.

“Almost half of American women have dense breasts and why that is significant is because the dense breast issue not only increases one’s risk of getting breast cancer, but it also can hide small breast cancers on the mammogram,” she said.

If you take 1,000 women with dense breasts and then do a breast ultrasound as a supplemental screening measure, “you will find three more small node-negative breast cancers that would not have come to light if you didn’t do the extra supplemental screening,” underscoring the importance of communicating dense breast information, she continued.

FDA also is seeking to enhance information provided to health care professionals by codifying three additional categories for mammogram assessments, including the addition of the “known biopsy proven malignancy” category, which the agency says would help identify which scans were being used to evaluate treatment of already diagnosed cancers.

Both patients and health care professionals would receive more detailed information about the mammography facility under the proposed rule.

FDA is proposing modernization of quality standards to help the agency enforce regulations, including giving the agency the authority to notify patients and health care professionals directly if a mammography facility does not meet quality standards and that a reevaluation or repeat of the exam at a different facility may be needed. The proposed amendments also include requiring that only digital accessory components specifically FDA approved or cleared for mammography be used or that facilities use components that otherwise meet the requirements, and stronger record-keeping requirements.

Dr. Margolies did note one potential deficiency in the proposed rule – the lack of any information on health insurance coverage of supplemental screening for women with dense breasts, though she noted this may not fall under the FDA’s authority.

“It would do the most good if everybody could get the supplemental screening without regards to their ability to pay for it out of pocket,” she said.

The proposal amends regulations issued under the Mammography Quality Standards Act of 1992, which gives FDA oversight authority over mammography facilities, including accreditation, certification, annual inspection, and enforcement of standards.

Comments on the proposal are due 90 days after the proposed rule is published in the Federal Register, which is scheduled for March 28.

[email protected]

For women with metastatic hormone receptor–positive breast cancer, the addition of the selective estrogen receptor modifier fulvestrant (Faslodex) to the aromatase inhibitor anastrozole (Arimidex and generics) resulted in a small but significant improvement in overall survival, according to final results from a randomized phase 3 trial.

Among 694 patients randomized for whom data were available, the hazard ratio for death with the combination when compared with anastrozole alone was 0.82 (P = .03), reported Rita S. Mehta, MD, from the University of California (Irvine) Medical Center and her colleagues.

The benefit of the combination was highest for patients without prior exposure to adjuvant endocrine therapy.

“Furthermore, sequential therapy with anastrozole and fulvestrant (45% of patients crossed over to fulvestrant alone) did not negate the significance of the long-term overall survival benefit with the combination therapy as compared with anastrozole,” the investigators wrote in The New England Journal of Medicine.

The current report is the final survival analysis of the trial. The primary results were reported in 2012 (N Engl J Med. 2012; 367:435-44). A total of 707 postmenopausal women with previously untreated metastatic disease were randomly assigned to receive either 1 mg of anastrozole orally every day with crossover to fulvestrant alone strongly encouraged if the disease progressed or to anastrozole and fulvestrant in combination. Randomization was stratified according to prior adjuvant tamoxifen use. A total of 694 women had data available for analysis.

The primary analysis, conducted at a median follow-up of 35 months, showed a median progression-free survival (PFS) with anastrozole alone of 13.5 months, compared with 15.0 months for anastrozole/fulvestrant (HR for progression or death 0.80; P = .007). Respective median overall survival was 41.3 months and 47.7 months (HR for death 0.81; P = .05).

The current, final analysis, conducted at a median follow-up of 7 years in patients who did not have disease progression, showed 261 deaths among 345 women (76%) in the anastrozole-only group, compared with 247 deaths among 349 women (71%) in the combination group (HR for death 0.82; P = .03).

Overall survival was longer for those women who had not previously received tamoxifen who were treated with the combination, at a median of 52.2 months versus 40.3 months for women not previously treated with tamoxifen who received anastrozole alone (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92). In contrast, there was no significant difference in OS between the two treatment groups in women who had previously received tamoxifen.

Approximately 45% of patients initially randomized to anastrozole alone were crossed over to fulvestrant.

The incidence of long-term toxic effects and treatment-related deaths was similar between the groups. Previously reported treatment-related deaths with the combination included pulmonary emboli in two patients and a cerebrovascular ischemic event in one patients.

At the time of data cutoff for the final report, 15% of patients in the combination-therapy group and 13% in the anastrozole-only group had experienced grade 3 toxicities.

The study was supported by National Cancer Institute grants and by AstraZeneca. Dr. Mehta reported institutional and personal grants from AstraZeneca and others. Multiple coauthors reported similar relationships.

SOURCE: Mehta RS et al. N Engl J Med. 2019;380:1226-34.

For women with metastatic hormone receptor–positive breast cancer, the addition of the selective estrogen receptor modifier fulvestrant (Faslodex) to the aromatase inhibitor anastrozole (Arimidex and generics) resulted in a small but significant improvement in overall survival, according to final results from a randomized phase 3 trial.

Among 694 patients randomized for whom data were available, the hazard ratio for death with the combination when compared with anastrozole alone was 0.82 (P = .03), reported Rita S. Mehta, MD, from the University of California (Irvine) Medical Center and her colleagues.

The benefit of the combination was highest for patients without prior exposure to adjuvant endocrine therapy.

“Furthermore, sequential therapy with anastrozole and fulvestrant (45% of patients crossed over to fulvestrant alone) did not negate the significance of the long-term overall survival benefit with the combination therapy as compared with anastrozole,” the investigators wrote in The New England Journal of Medicine.

The current report is the final survival analysis of the trial. The primary results were reported in 2012 (N Engl J Med. 2012; 367:435-44). A total of 707 postmenopausal women with previously untreated metastatic disease were randomly assigned to receive either 1 mg of anastrozole orally every day with crossover to fulvestrant alone strongly encouraged if the disease progressed or to anastrozole and fulvestrant in combination. Randomization was stratified according to prior adjuvant tamoxifen use. A total of 694 women had data available for analysis.

The primary analysis, conducted at a median follow-up of 35 months, showed a median progression-free survival (PFS) with anastrozole alone of 13.5 months, compared with 15.0 months for anastrozole/fulvestrant (HR for progression or death 0.80; P = .007). Respective median overall survival was 41.3 months and 47.7 months (HR for death 0.81; P = .05).

The current, final analysis, conducted at a median follow-up of 7 years in patients who did not have disease progression, showed 261 deaths among 345 women (76%) in the anastrozole-only group, compared with 247 deaths among 349 women (71%) in the combination group (HR for death 0.82; P = .03).

Overall survival was longer for those women who had not previously received tamoxifen who were treated with the combination, at a median of 52.2 months versus 40.3 months for women not previously treated with tamoxifen who received anastrozole alone (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92). In contrast, there was no significant difference in OS between the two treatment groups in women who had previously received tamoxifen.

Approximately 45% of patients initially randomized to anastrozole alone were crossed over to fulvestrant.

The incidence of long-term toxic effects and treatment-related deaths was similar between the groups. Previously reported treatment-related deaths with the combination included pulmonary emboli in two patients and a cerebrovascular ischemic event in one patients.

At the time of data cutoff for the final report, 15% of patients in the combination-therapy group and 13% in the anastrozole-only group had experienced grade 3 toxicities.

The study was supported by National Cancer Institute grants and by AstraZeneca. Dr. Mehta reported institutional and personal grants from AstraZeneca and others. Multiple coauthors reported similar relationships.

SOURCE: Mehta RS et al. N Engl J Med. 2019;380:1226-34.

For women with metastatic hormone receptor–positive breast cancer, the addition of the selective estrogen receptor modifier fulvestrant (Faslodex) to the aromatase inhibitor anastrozole (Arimidex and generics) resulted in a small but significant improvement in overall survival, according to final results from a randomized phase 3 trial.

Among 694 patients randomized for whom data were available, the hazard ratio for death with the combination when compared with anastrozole alone was 0.82 (P = .03), reported Rita S. Mehta, MD, from the University of California (Irvine) Medical Center and her colleagues.

The benefit of the combination was highest for patients without prior exposure to adjuvant endocrine therapy.

“Furthermore, sequential therapy with anastrozole and fulvestrant (45% of patients crossed over to fulvestrant alone) did not negate the significance of the long-term overall survival benefit with the combination therapy as compared with anastrozole,” the investigators wrote in The New England Journal of Medicine.

The current report is the final survival analysis of the trial. The primary results were reported in 2012 (N Engl J Med. 2012; 367:435-44). A total of 707 postmenopausal women with previously untreated metastatic disease were randomly assigned to receive either 1 mg of anastrozole orally every day with crossover to fulvestrant alone strongly encouraged if the disease progressed or to anastrozole and fulvestrant in combination. Randomization was stratified according to prior adjuvant tamoxifen use. A total of 694 women had data available for analysis.

The primary analysis, conducted at a median follow-up of 35 months, showed a median progression-free survival (PFS) with anastrozole alone of 13.5 months, compared with 15.0 months for anastrozole/fulvestrant (HR for progression or death 0.80; P = .007). Respective median overall survival was 41.3 months and 47.7 months (HR for death 0.81; P = .05).

The current, final analysis, conducted at a median follow-up of 7 years in patients who did not have disease progression, showed 261 deaths among 345 women (76%) in the anastrozole-only group, compared with 247 deaths among 349 women (71%) in the combination group (HR for death 0.82; P = .03).

Overall survival was longer for those women who had not previously received tamoxifen who were treated with the combination, at a median of 52.2 months versus 40.3 months for women not previously treated with tamoxifen who received anastrozole alone (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92). In contrast, there was no significant difference in OS between the two treatment groups in women who had previously received tamoxifen.

Approximately 45% of patients initially randomized to anastrozole alone were crossed over to fulvestrant.

The incidence of long-term toxic effects and treatment-related deaths was similar between the groups. Previously reported treatment-related deaths with the combination included pulmonary emboli in two patients and a cerebrovascular ischemic event in one patients.

At the time of data cutoff for the final report, 15% of patients in the combination-therapy group and 13% in the anastrozole-only group had experienced grade 3 toxicities.

The study was supported by National Cancer Institute grants and by AstraZeneca. Dr. Mehta reported institutional and personal grants from AstraZeneca and others. Multiple coauthors reported similar relationships.

SOURCE: Mehta RS et al. N Engl J Med. 2019;380:1226-34.

A qualitative study representing the patient perspective provides insight on reducing economic burden after breast cancer, including specific recommendations for changes to insurance, supportive services, financial assistance, and protective policies.

As part of a 6-month observational study conducted in 2015, Lorraine T. Dean, ScD, of Johns Hopkins Schools of Public Health and Medicine, Baltimore, and her associates, interviewed 40 women diagnosed with invasive stage I-III breast cancer who had completed active cancer treatment. All patients, who reported having more than one lymph node removed resided in Pennsylvania or New Jersey. The mean age of the women was 64 years.

Of those interviewed, 53% were white; 42.5% were black. More than half of participants (53%) were college graduates or had received a graduate degree. Annual income for 58% of the patients ranged from $30,000 to $70,000; 11% earned under $30,000. All participants included in the study were insured, including 82.5% who had private insurance. The patients had been diagnosed a mean of 12 years prior. Breast cancer–related lymphedema was reported in 60% of patients, Dr. Dean and her associates reported in a report published in Cancer.

Among the 40 participants, 27 made recommendations for easing economic burden, including nine key recommendations across four significant areas: insurance, supportive services and care, financial assistance, and protective policies. These findings are consistent with previous studies that examined patient recommendations, but they address additional areas where cost-saving services and policies could be offered or improved upon, the investigators noted.

Insurance-related recommendations included offering more complementary and integrative treatments as well as helping patients understand what insurance plans cover and how to adjust to changes under new insurance plans. Providing high-quality plans with low copays, premiums, and deductibles that cover required as well as elective cancer-related services, and covering lymphedema-related materials and treatments also were flagged as important.

Supportive service recommendations included addressing psychosocial costs through expansion of support groups and buddy services, offering extended home health services following cancer treatment, and providing domestic assistance with household chores, child care, and transportation.

Financial assistance that broadens financial aid and social services eligibility to those not classified as being in poverty was considered important.

Protective policy recommendations focused on expanding employment and medical leave policies concerning the amount of time offered off from work.

Patient recommendations offer just one viewpoint concerning potential challenges to the overall system, but “their thoughts on how it can be improved add value to decision-making processes,” noted Dr. Dean and her associates.

They were careful to acknowledge the benefits of the Patient Protection and Affordable Care Act, but they noted that it does not include provisions to address the adverse treatment effects of conditions such as cancer. While some states already have successfully passed legislation requiring private insurance carriers to cover lymphedema treatment, similar legislation should be adopted at a national level through joint efforts of Congress and the Department of Labor, they advised.

Any such efforts to make sweeping changes within the insurance industry would take considerable effort on the part of patients, providers, insurers, and state and federal policy makers, as well as the pharmaceutical industry. Yet, such “top-down and bottom-up strategies that involve all parties are warranted,” they urged.

Several important limitations of the study are worth noting. All participants were from the East Coast, had insurance coverage, and reported an overall low level of economic burden. Responses may have differed had the study been conducted in other regions of the country. The study was voluntary, so it is important to consider that patients with greater financial challenges may not have had time to enroll and participate, which suggests that the level of economic burden affecting this population actually could be understated.

SOURCE: Dean LT et al. Cancer 2019 Mar 6. doi: 10.1002/cncr.32012.

A qualitative study representing the patient perspective provides insight on reducing economic burden after breast cancer, including specific recommendations for changes to insurance, supportive services, financial assistance, and protective policies.

As part of a 6-month observational study conducted in 2015, Lorraine T. Dean, ScD, of Johns Hopkins Schools of Public Health and Medicine, Baltimore, and her associates, interviewed 40 women diagnosed with invasive stage I-III breast cancer who had completed active cancer treatment. All patients, who reported having more than one lymph node removed resided in Pennsylvania or New Jersey. The mean age of the women was 64 years.

Of those interviewed, 53% were white; 42.5% were black. More than half of participants (53%) were college graduates or had received a graduate degree. Annual income for 58% of the patients ranged from $30,000 to $70,000; 11% earned under $30,000. All participants included in the study were insured, including 82.5% who had private insurance. The patients had been diagnosed a mean of 12 years prior. Breast cancer–related lymphedema was reported in 60% of patients, Dr. Dean and her associates reported in a report published in Cancer.

Among the 40 participants, 27 made recommendations for easing economic burden, including nine key recommendations across four significant areas: insurance, supportive services and care, financial assistance, and protective policies. These findings are consistent with previous studies that examined patient recommendations, but they address additional areas where cost-saving services and policies could be offered or improved upon, the investigators noted.

Insurance-related recommendations included offering more complementary and integrative treatments as well as helping patients understand what insurance plans cover and how to adjust to changes under new insurance plans. Providing high-quality plans with low copays, premiums, and deductibles that cover required as well as elective cancer-related services, and covering lymphedema-related materials and treatments also were flagged as important.

Supportive service recommendations included addressing psychosocial costs through expansion of support groups and buddy services, offering extended home health services following cancer treatment, and providing domestic assistance with household chores, child care, and transportation.

Financial assistance that broadens financial aid and social services eligibility to those not classified as being in poverty was considered important.

Protective policy recommendations focused on expanding employment and medical leave policies concerning the amount of time offered off from work.

Patient recommendations offer just one viewpoint concerning potential challenges to the overall system, but “their thoughts on how it can be improved add value to decision-making processes,” noted Dr. Dean and her associates.

They were careful to acknowledge the benefits of the Patient Protection and Affordable Care Act, but they noted that it does not include provisions to address the adverse treatment effects of conditions such as cancer. While some states already have successfully passed legislation requiring private insurance carriers to cover lymphedema treatment, similar legislation should be adopted at a national level through joint efforts of Congress and the Department of Labor, they advised.

Any such efforts to make sweeping changes within the insurance industry would take considerable effort on the part of patients, providers, insurers, and state and federal policy makers, as well as the pharmaceutical industry. Yet, such “top-down and bottom-up strategies that involve all parties are warranted,” they urged.

Several important limitations of the study are worth noting. All participants were from the East Coast, had insurance coverage, and reported an overall low level of economic burden. Responses may have differed had the study been conducted in other regions of the country. The study was voluntary, so it is important to consider that patients with greater financial challenges may not have had time to enroll and participate, which suggests that the level of economic burden affecting this population actually could be understated.

SOURCE: Dean LT et al. Cancer 2019 Mar 6. doi: 10.1002/cncr.32012.

A qualitative study representing the patient perspective provides insight on reducing economic burden after breast cancer, including specific recommendations for changes to insurance, supportive services, financial assistance, and protective policies.

As part of a 6-month observational study conducted in 2015, Lorraine T. Dean, ScD, of Johns Hopkins Schools of Public Health and Medicine, Baltimore, and her associates, interviewed 40 women diagnosed with invasive stage I-III breast cancer who had completed active cancer treatment. All patients, who reported having more than one lymph node removed resided in Pennsylvania or New Jersey. The mean age of the women was 64 years.

Of those interviewed, 53% were white; 42.5% were black. More than half of participants (53%) were college graduates or had received a graduate degree. Annual income for 58% of the patients ranged from $30,000 to $70,000; 11% earned under $30,000. All participants included in the study were insured, including 82.5% who had private insurance. The patients had been diagnosed a mean of 12 years prior. Breast cancer–related lymphedema was reported in 60% of patients, Dr. Dean and her associates reported in a report published in Cancer.

Among the 40 participants, 27 made recommendations for easing economic burden, including nine key recommendations across four significant areas: insurance, supportive services and care, financial assistance, and protective policies. These findings are consistent with previous studies that examined patient recommendations, but they address additional areas where cost-saving services and policies could be offered or improved upon, the investigators noted.

Insurance-related recommendations included offering more complementary and integrative treatments as well as helping patients understand what insurance plans cover and how to adjust to changes under new insurance plans. Providing high-quality plans with low copays, premiums, and deductibles that cover required as well as elective cancer-related services, and covering lymphedema-related materials and treatments also were flagged as important.

Supportive service recommendations included addressing psychosocial costs through expansion of support groups and buddy services, offering extended home health services following cancer treatment, and providing domestic assistance with household chores, child care, and transportation.

Financial assistance that broadens financial aid and social services eligibility to those not classified as being in poverty was considered important.

Protective policy recommendations focused on expanding employment and medical leave policies concerning the amount of time offered off from work.

Patient recommendations offer just one viewpoint concerning potential challenges to the overall system, but “their thoughts on how it can be improved add value to decision-making processes,” noted Dr. Dean and her associates.

They were careful to acknowledge the benefits of the Patient Protection and Affordable Care Act, but they noted that it does not include provisions to address the adverse treatment effects of conditions such as cancer. While some states already have successfully passed legislation requiring private insurance carriers to cover lymphedema treatment, similar legislation should be adopted at a national level through joint efforts of Congress and the Department of Labor, they advised.

Any such efforts to make sweeping changes within the insurance industry would take considerable effort on the part of patients, providers, insurers, and state and federal policy makers, as well as the pharmaceutical industry. Yet, such “top-down and bottom-up strategies that involve all parties are warranted,” they urged.

Several important limitations of the study are worth noting. All participants were from the East Coast, had insurance coverage, and reported an overall low level of economic burden. Responses may have differed had the study been conducted in other regions of the country. The study was voluntary, so it is important to consider that patients with greater financial challenges may not have had time to enroll and participate, which suggests that the level of economic burden affecting this population actually could be understated.

SOURCE: Dean LT et al. Cancer 2019 Mar 6. doi: 10.1002/cncr.32012.

The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.

The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.

The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.