M. Alexander Otto, PA, MMS

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved the gene therapy valoctocogene roxaparvovec (Roctavian, BioMarin) for adults with severe hemophilia A.

Valoctocogene roxaparvovec, a one-time, single-dose IV infusion, is the first gene therapy approved in the United States for severe hemophilia A and will cost around $2.9 million. BioMarin has said the price tag reflects “the possibility of freedom from years” of infusions, which come to about $800,000 each year.

However, last December, the Institute for Clinical and Economic Review (ICER) set the upper bounds for the gene therapy at about $1.96 million. The extent to which the gene therapy will provide freedom from infusions, for how long, and in which patients are not completely understood.

Hemophilia A is caused by a mutation in the gene that produces a protein called coagulation factor VIII, which is essential for blood clotting. Valoctocogene roxaparvovec delivers a functional gene to liver cells via an adeno-associated virus serotype 5; the gene instructs the cells to make the missing clotting factor.

“Adults with severe hemophilia A face a lifelong burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreversible joint damage,” Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, and an investigator for the phase 3 study that led to the approval, said in a statement. The approval of valoctocogene roxaparvovec “has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

About 6,500 U.S. adults live with severe hemophilia A, and BioMarin said it anticipates approximately 2,500 will be eligible to receive the gene therapy following the approval. The U.S. indication is limited to patients without a history of factor VIII inhibitors and without detectable antibodies to the adeno-associated virus serotype 5.

Last August, the European Medicines Agency authorized the gene therapy for use in Europe, but according to Forbes and PharmaPhorum, uptake in Europe has been delayed because of reimbursement issues, given the cost of treatment and clinical uncertainties.

Data to date, however, are promising for most patients. Approval was based on BioMarin’s open-label, single-arm GENEr8-1 study in 134 men with severe congenital hemophilia A. Patients received a single infusion of 6 x 10¹³ vector genomes per kilogram.

Among the 132 patients available for 2-year evaluation, median factor VIII activity was in the range for mild hemophilia (6%-39% of normal) with an 84.5% reduction in bleeding events from baseline.

More than 80% of participants had no bleeding events requiring treatment, and there was a 98% reduction from baseline in mean use of exogenous factor VIII.

Overall, at 2 years, only 4.5% of patients had factor VIII activity consistent with severe hemophilia A; 9.1% had activity consistent with moderate disease; 59.8% had activity consistent with mild disease, and 26.5% had activity in the normal range above 40 IU/dL.

Trial investigators estimated that the typical half-life of the transgene-derived factor VIII production system is 123 weeks.

Among the six men who resumed prophylaxis, most had fewer bleeding events than when they were on prophylaxis before the infusion. All patients developed antibodies to the virus delivery vector, precluding retreatment.

Elevated alanine aminotransferase levels were the most common adverse event, occurring in 88.8% of patients, who were treated with immunosuppressants for a median of 33 weeks. Elevations persisted at 2 years in 29% of patients.

The other most common adverse events were headache (38.1%), nausea (37.3%), and increases in aspartate aminotransferase (35.1%).

A version of this article first appeared on Medscape.com.

Guidelines recommend chemoradiation (CRT) before surgery for patients with clinical stage II-III rectal cancer in order to lower the risk of locoregional recurrence, but there is a growing concern among oncologists that the approach leads to overtreatment.

However, the issue has been how best to identify patients who would do well with less intensive treatment.

A German team reported a promising approach to this issue, describing the use of preoperative MRI to assess the mesorectal fascia (MRF) for the presence of a tumor. The paper was published in the Journal of Clinical Oncology.

The thinking is that with uninvolved MRF, the tumor is removed by total mesorectal excision (TME) alone, while patients with involved MRF need neoadjuvant chemoradiation therapy to shrink the tumor before resection.

The team put the idea to the test in 884 patients with cT2-4 rectal cancer.

There were 530 patients (60%) with clear MRFs, and they proceeded directly to total mesorectal excision. The 5-year locoregional recurrence rate was just 2.9% in this group.

In comparison, almost 6% of the 354 patients who received neoadjuvant CRT in this study had a locoregional recurrence within 5 years of TME.

Neoadjuvant chemoradiation offers “no advantage over optimized surgery” for such patients “if a 5-year [locoregional recurrence] rate of approximately 5% is acceptable,” said investigators, led by Reinhard Ruppert, MD, of the department of general and visceral surgery, endocrine surgery, and coloproctology at the Municipal Hospital of Munich-Neuperlach.

If so, neoadjuvant chemoradiation “and its adverse effects can be avoided in 60% of the total population and in 45% of patients with clinical stage II and III cancer” as found in the study, they said.

“The risk of undertreatment because of the omission of” neoadjuvant chemoradiation is low, they commented. Of the 10 patients who had a negative MRF but turned out to have positive resection margins at surgery, only one had a recurrence, the team noted.

Overall, the study suggests that neoadjuvant chemoradiation therapy can be restricted to patients at high risk of locoregional recurrence. “These findings may be used for guiding clinical surgical practice and the administration of neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy,” the investigators said.
 

Concern about reproducibility

Approached for comment, Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, said, “This is another paper that pretty much confirms the assumption that we overtreat many patients with rectal cancer.”

These “data support the principle that many, if not most, patients with localized rectal cancer do not require trimodality therapy (chemotherapy, radiation, surgery) to achieve cure. That said, it remains a real challenge to figure out which of the modalities can or should be omitted in the average patient,” Dr. Venook told this news organization.

Overall, the German results “are excellent” but it’s unknown if the results can be replicated in community settings, given the expertise needed to discern MRF involvement on MRI and the fact that not every patient gets TME, the gold-standard surgery used in the trial, he said.

Venook said that at his university, given the rapidly evolving literature on de-escalating treatment, every rectal cancer case is discussed at a multidisciplinary tumor board to decide the best course of action.
 

Study details

Patients in the trial were treated at 14 centers in Germany from 2007 to 2016; nodal involvement was allowed, but subjects had no distant metastases. The call on whether or not they had MRF involvement was based on the distance between the MRF on preoperative MRI and their tumor, suspicious lymph nodes, and tumor deposits.

Patients with a distance greater than 1 mm were considered low risk for recurrence and underwent upfront total mesorectal excision. Those with a distance of 1 mm or fewer as well as patients with cT4 tumors and cT3 tumors in the lower rectal third – a location that makes it difficult to assess the MRF involvement – received up to 50.4 Gy radiation plus fluorouracil before surgery.

The 5-year rate of distant metastases was 15.9% in the upfront surgery group versus 30.5% in the nCRT arm; 11% of the upfront surgery group died of rectal cancer during follow-up versus 21.8% of the nCRT arm.

The work was funded by Johannes Gutenberg University Mainz. Dr. Ruppert and Dr. Venook report no relevant financial relationships. Three investigators reported honoraria and/or travel expenses from Intuitive Surgical, AbbVie, Johnson & Johnson, and other companies.

A version of this article originally appeared on Medscape.com.

Guidelines recommend chemoradiation (CRT) before surgery for patients with clinical stage II-III rectal cancer in order to lower the risk of locoregional recurrence, but there is a growing concern among oncologists that the approach leads to overtreatment.

However, the issue has been how best to identify patients who would do well with less intensive treatment.

A German team reported a promising approach to this issue, describing the use of preoperative MRI to assess the mesorectal fascia (MRF) for the presence of a tumor. The paper was published in the Journal of Clinical Oncology.

The thinking is that with uninvolved MRF, the tumor is removed by total mesorectal excision (TME) alone, while patients with involved MRF need neoadjuvant chemoradiation therapy to shrink the tumor before resection.

The team put the idea to the test in 884 patients with cT2-4 rectal cancer.

There were 530 patients (60%) with clear MRFs, and they proceeded directly to total mesorectal excision. The 5-year locoregional recurrence rate was just 2.9% in this group.

In comparison, almost 6% of the 354 patients who received neoadjuvant CRT in this study had a locoregional recurrence within 5 years of TME.

Neoadjuvant chemoradiation offers “no advantage over optimized surgery” for such patients “if a 5-year [locoregional recurrence] rate of approximately 5% is acceptable,” said investigators, led by Reinhard Ruppert, MD, of the department of general and visceral surgery, endocrine surgery, and coloproctology at the Municipal Hospital of Munich-Neuperlach.

If so, neoadjuvant chemoradiation “and its adverse effects can be avoided in 60% of the total population and in 45% of patients with clinical stage II and III cancer” as found in the study, they said.

“The risk of undertreatment because of the omission of” neoadjuvant chemoradiation is low, they commented. Of the 10 patients who had a negative MRF but turned out to have positive resection margins at surgery, only one had a recurrence, the team noted.

Overall, the study suggests that neoadjuvant chemoradiation therapy can be restricted to patients at high risk of locoregional recurrence. “These findings may be used for guiding clinical surgical practice and the administration of neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy,” the investigators said.
 

Concern about reproducibility

Approached for comment, Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, said, “This is another paper that pretty much confirms the assumption that we overtreat many patients with rectal cancer.”

These “data support the principle that many, if not most, patients with localized rectal cancer do not require trimodality therapy (chemotherapy, radiation, surgery) to achieve cure. That said, it remains a real challenge to figure out which of the modalities can or should be omitted in the average patient,” Dr. Venook told this news organization.

Overall, the German results “are excellent” but it’s unknown if the results can be replicated in community settings, given the expertise needed to discern MRF involvement on MRI and the fact that not every patient gets TME, the gold-standard surgery used in the trial, he said.

Venook said that at his university, given the rapidly evolving literature on de-escalating treatment, every rectal cancer case is discussed at a multidisciplinary tumor board to decide the best course of action.
 

Study details

Patients in the trial were treated at 14 centers in Germany from 2007 to 2016; nodal involvement was allowed, but subjects had no distant metastases. The call on whether or not they had MRF involvement was based on the distance between the MRF on preoperative MRI and their tumor, suspicious lymph nodes, and tumor deposits.

Patients with a distance greater than 1 mm were considered low risk for recurrence and underwent upfront total mesorectal excision. Those with a distance of 1 mm or fewer as well as patients with cT4 tumors and cT3 tumors in the lower rectal third – a location that makes it difficult to assess the MRF involvement – received up to 50.4 Gy radiation plus fluorouracil before surgery.

The 5-year rate of distant metastases was 15.9% in the upfront surgery group versus 30.5% in the nCRT arm; 11% of the upfront surgery group died of rectal cancer during follow-up versus 21.8% of the nCRT arm.

The work was funded by Johannes Gutenberg University Mainz. Dr. Ruppert and Dr. Venook report no relevant financial relationships. Three investigators reported honoraria and/or travel expenses from Intuitive Surgical, AbbVie, Johnson & Johnson, and other companies.

A version of this article originally appeared on Medscape.com.

Guidelines recommend chemoradiation (CRT) before surgery for patients with clinical stage II-III rectal cancer in order to lower the risk of locoregional recurrence, but there is a growing concern among oncologists that the approach leads to overtreatment.

However, the issue has been how best to identify patients who would do well with less intensive treatment.

A German team reported a promising approach to this issue, describing the use of preoperative MRI to assess the mesorectal fascia (MRF) for the presence of a tumor. The paper was published in the Journal of Clinical Oncology.

The thinking is that with uninvolved MRF, the tumor is removed by total mesorectal excision (TME) alone, while patients with involved MRF need neoadjuvant chemoradiation therapy to shrink the tumor before resection.

The team put the idea to the test in 884 patients with cT2-4 rectal cancer.

There were 530 patients (60%) with clear MRFs, and they proceeded directly to total mesorectal excision. The 5-year locoregional recurrence rate was just 2.9% in this group.

In comparison, almost 6% of the 354 patients who received neoadjuvant CRT in this study had a locoregional recurrence within 5 years of TME.

Neoadjuvant chemoradiation offers “no advantage over optimized surgery” for such patients “if a 5-year [locoregional recurrence] rate of approximately 5% is acceptable,” said investigators, led by Reinhard Ruppert, MD, of the department of general and visceral surgery, endocrine surgery, and coloproctology at the Municipal Hospital of Munich-Neuperlach.

If so, neoadjuvant chemoradiation “and its adverse effects can be avoided in 60% of the total population and in 45% of patients with clinical stage II and III cancer” as found in the study, they said.

“The risk of undertreatment because of the omission of” neoadjuvant chemoradiation is low, they commented. Of the 10 patients who had a negative MRF but turned out to have positive resection margins at surgery, only one had a recurrence, the team noted.

Overall, the study suggests that neoadjuvant chemoradiation therapy can be restricted to patients at high risk of locoregional recurrence. “These findings may be used for guiding clinical surgical practice and the administration of neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy,” the investigators said.
 

Concern about reproducibility

Approached for comment, Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, said, “This is another paper that pretty much confirms the assumption that we overtreat many patients with rectal cancer.”

These “data support the principle that many, if not most, patients with localized rectal cancer do not require trimodality therapy (chemotherapy, radiation, surgery) to achieve cure. That said, it remains a real challenge to figure out which of the modalities can or should be omitted in the average patient,” Dr. Venook told this news organization.

Overall, the German results “are excellent” but it’s unknown if the results can be replicated in community settings, given the expertise needed to discern MRF involvement on MRI and the fact that not every patient gets TME, the gold-standard surgery used in the trial, he said.

Venook said that at his university, given the rapidly evolving literature on de-escalating treatment, every rectal cancer case is discussed at a multidisciplinary tumor board to decide the best course of action.
 

Study details

Patients in the trial were treated at 14 centers in Germany from 2007 to 2016; nodal involvement was allowed, but subjects had no distant metastases. The call on whether or not they had MRF involvement was based on the distance between the MRF on preoperative MRI and their tumor, suspicious lymph nodes, and tumor deposits.

Patients with a distance greater than 1 mm were considered low risk for recurrence and underwent upfront total mesorectal excision. Those with a distance of 1 mm or fewer as well as patients with cT4 tumors and cT3 tumors in the lower rectal third – a location that makes it difficult to assess the MRF involvement – received up to 50.4 Gy radiation plus fluorouracil before surgery.

The 5-year rate of distant metastases was 15.9% in the upfront surgery group versus 30.5% in the nCRT arm; 11% of the upfront surgery group died of rectal cancer during follow-up versus 21.8% of the nCRT arm.

The work was funded by Johannes Gutenberg University Mainz. Dr. Ruppert and Dr. Venook report no relevant financial relationships. Three investigators reported honoraria and/or travel expenses from Intuitive Surgical, AbbVie, Johnson & Johnson, and other companies.

A version of this article originally appeared on Medscape.com.

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

A version of this article first appeared on Medscape.com.

The common side effect of hand-foot syndrome seen in patients taking capecitabine can be prevented with a cheap and safe topical gel containing 1% diclofenac, researchers reported in a study that has been hailed by experts as “practice changing.”

Hand-foot syndrome causes painful, bleeding blisters and ulcers on the palms and soles. It often leads to dose reductions and sometimes even discontinuations, both of which limit the effectiveness of capecitabine, a standard oral chemotherapy drug widely used for colorectal and breast  cancers.

In a new study presented at the annual meeting of the American Society of Clinical Oncology, Indian researchers reported that a cheap, safe, and widely available over-the-counter nonsteroidal anti-inflammatory gel containing 1% diclofenac reduced the incidence of hand-foot syndrome by 75% among patients with cancer being treated with capecitabine.

Up until now, the oral anti-inflammatory celecoxib (Celebrex) was the only agent proven to prevent the problem, but it’s rarely used because of the risk for strokes, gastric bleeding, and other issues, none of which are a concern with topical diclofenac, which osteoarthritis patients have used safely for years.

The Indian trial, dubbed D-Torch, establishes “1% topical diclofenac gel as the new standard of care to prevent capecitabine-associated hand-foot syndrome,” said investigator and study presenter Atul Batra, MD, a medical oncologist at the All India Institute of Medical Sciences, New Delhi.

Dr. Batra told ASCO Daily News that there is no need for a second trial. “We don’t feel there’s a need to replicate these results” in a larger study “because this was adequately powered, and the results speak for themselves. There’s no confusion about these results. Diclofenac is clearly effective.”

Dr. Batra also commented that his clinic now uses topical diclofenac routinely during capecitabine treatment and that he hopes oncology practices elsewhere will do the same.   

Diclofenac gel is sold under the brand name Voltaren and is also available as a generic; in the United States, a 150-gram tube costs about $18 at Walmart.
 

‘The most practice-changing study’ at ASCO 2023

Audience members at ASCO’s annual meeting immediately saw the importance of the study.

Tarah Ballinger, MD, a breast cancer specialist at Indiana University, Indianapolis, said on Twitter that “this might be the most practice changing study I heard at ASCO23.” Topical diclofenac is “widely available, affordable, [and] addresses [a] major” quality of life issue.

The study discussant at the meeting, gastrointestinal cancer specialist Pallavi Kumar, MD, of the University of Pennsylvania, Philadelphia, concurred: “For me as a GI oncologist, topical diclofenac for prevention of HFS for patients on capecitabine is practice changing,” she said.

The takeaway is “that topical diclofenac significantly reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine.” The results are “very impressive,” Dr. Kumar said.

Study details

The idea for the new study came after Batra and colleagues realized that celecoxib, a COX-2 enzyme inhibitor, helps prevent capecitabine hand-foot syndrome (HFS) by blocking a key process that leads to it, the up-regulation of COX-2 and subsequent release of proinflammatory prostaglandins.

They turned to diclofenac gel hoping to get the same effect but more safely; diclofenac is also a COX-2 blocker, and its topical formulation has a strong safety record. 

To test the approach, the team randomly assigned 130 patients to topical diclofenac and 133 to placebo – the gel vehicle without the medication – while they were being treated with capecitabine for 12 weeks; 56% were being treated for breast cancer and the rest for gastrointestinal cancers.

Subjects rubbed one fingertip’s worth of gel – about half a gram – on each palm and the back of each hand twice a day. The dose was about 4 grams/day, which is well below maximal dosages for osteoarthritis (up to 32 g/day over all affected joints). Adherence to treatment was about 95% in both arms.

By the end of 12 weeks, the incidence of grade 2 or higher HFS was 3.8% in the diclofenac arm (5 patients) versus 15% (n = 20) with placebo (P = .003), a 75% risk reduction.

The incidence of any grade HFS was 6.1% in the treatment group versus 18.1% with placebo (P = .003).

Hand-foot syndrome led to dose reductions of capecitabine in 13.5% of placebo but only 3.8% of those in the diclofenac group (P = .002). 

The findings held regardless of whether patients were being treated for breast or GI cancer or if they were men or women. 

Other capecitabine-induced adverse events, including diarrhea, mucositis, and myelosuppression, were not significantly different between the groups.

The treatment arms were well balanced, with a median age of 47 years in both groups and women making up about 70% of each. About 40% of subjects in each group were on capecitabine monotherapy with the rest on combination treatments. The mean dose of capecitabine was just over 1,880 mg/m² in both groups.

At the meeting, Dr. Batra was asked if topical diclofenac would also work for another common problem in oncology: hand-food syndrome occurring as a side-effect with VEGF–tyrosine kinase inhibitors. He didn’t think so because it probably has a different cause than capecitabine HFS, one not strongly related to COX-2 up-regulation.

The study was partly funded by the Indian Supportive Care of Cancer Association. The investigators reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The common side effect of hand-foot syndrome seen in patients taking capecitabine can be prevented with a cheap and safe topical gel containing 1% diclofenac, researchers reported in a study that has been hailed by experts as “practice changing.”

Hand-foot syndrome causes painful, bleeding blisters and ulcers on the palms and soles. It often leads to dose reductions and sometimes even discontinuations, both of which limit the effectiveness of capecitabine, a standard oral chemotherapy drug widely used for colorectal and breast  cancers.

In a new study presented at the annual meeting of the American Society of Clinical Oncology, Indian researchers reported that a cheap, safe, and widely available over-the-counter nonsteroidal anti-inflammatory gel containing 1% diclofenac reduced the incidence of hand-foot syndrome by 75% among patients with cancer being treated with capecitabine.

Up until now, the oral anti-inflammatory celecoxib (Celebrex) was the only agent proven to prevent the problem, but it’s rarely used because of the risk for strokes, gastric bleeding, and other issues, none of which are a concern with topical diclofenac, which osteoarthritis patients have used safely for years.

The Indian trial, dubbed D-Torch, establishes “1% topical diclofenac gel as the new standard of care to prevent capecitabine-associated hand-foot syndrome,” said investigator and study presenter Atul Batra, MD, a medical oncologist at the All India Institute of Medical Sciences, New Delhi.

Dr. Batra told ASCO Daily News that there is no need for a second trial. “We don’t feel there’s a need to replicate these results” in a larger study “because this was adequately powered, and the results speak for themselves. There’s no confusion about these results. Diclofenac is clearly effective.”

Dr. Batra also commented that his clinic now uses topical diclofenac routinely during capecitabine treatment and that he hopes oncology practices elsewhere will do the same.   

Diclofenac gel is sold under the brand name Voltaren and is also available as a generic; in the United States, a 150-gram tube costs about $18 at Walmart.
 

‘The most practice-changing study’ at ASCO 2023

Audience members at ASCO’s annual meeting immediately saw the importance of the study.

Tarah Ballinger, MD, a breast cancer specialist at Indiana University, Indianapolis, said on Twitter that “this might be the most practice changing study I heard at ASCO23.” Topical diclofenac is “widely available, affordable, [and] addresses [a] major” quality of life issue.

The study discussant at the meeting, gastrointestinal cancer specialist Pallavi Kumar, MD, of the University of Pennsylvania, Philadelphia, concurred: “For me as a GI oncologist, topical diclofenac for prevention of HFS for patients on capecitabine is practice changing,” she said.

The takeaway is “that topical diclofenac significantly reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine.” The results are “very impressive,” Dr. Kumar said.

Study details

The idea for the new study came after Batra and colleagues realized that celecoxib, a COX-2 enzyme inhibitor, helps prevent capecitabine hand-foot syndrome (HFS) by blocking a key process that leads to it, the up-regulation of COX-2 and subsequent release of proinflammatory prostaglandins.

They turned to diclofenac gel hoping to get the same effect but more safely; diclofenac is also a COX-2 blocker, and its topical formulation has a strong safety record. 

To test the approach, the team randomly assigned 130 patients to topical diclofenac and 133 to placebo – the gel vehicle without the medication – while they were being treated with capecitabine for 12 weeks; 56% were being treated for breast cancer and the rest for gastrointestinal cancers.

Subjects rubbed one fingertip’s worth of gel – about half a gram – on each palm and the back of each hand twice a day. The dose was about 4 grams/day, which is well below maximal dosages for osteoarthritis (up to 32 g/day over all affected joints). Adherence to treatment was about 95% in both arms.

By the end of 12 weeks, the incidence of grade 2 or higher HFS was 3.8% in the diclofenac arm (5 patients) versus 15% (n = 20) with placebo (P = .003), a 75% risk reduction.

The incidence of any grade HFS was 6.1% in the treatment group versus 18.1% with placebo (P = .003).

Hand-foot syndrome led to dose reductions of capecitabine in 13.5% of placebo but only 3.8% of those in the diclofenac group (P = .002). 

The findings held regardless of whether patients were being treated for breast or GI cancer or if they were men or women. 

Other capecitabine-induced adverse events, including diarrhea, mucositis, and myelosuppression, were not significantly different between the groups.

The treatment arms were well balanced, with a median age of 47 years in both groups and women making up about 70% of each. About 40% of subjects in each group were on capecitabine monotherapy with the rest on combination treatments. The mean dose of capecitabine was just over 1,880 mg/m² in both groups.

At the meeting, Dr. Batra was asked if topical diclofenac would also work for another common problem in oncology: hand-food syndrome occurring as a side-effect with VEGF–tyrosine kinase inhibitors. He didn’t think so because it probably has a different cause than capecitabine HFS, one not strongly related to COX-2 up-regulation.

The study was partly funded by the Indian Supportive Care of Cancer Association. The investigators reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The common side effect of hand-foot syndrome seen in patients taking capecitabine can be prevented with a cheap and safe topical gel containing 1% diclofenac, researchers reported in a study that has been hailed by experts as “practice changing.”

Hand-foot syndrome causes painful, bleeding blisters and ulcers on the palms and soles. It often leads to dose reductions and sometimes even discontinuations, both of which limit the effectiveness of capecitabine, a standard oral chemotherapy drug widely used for colorectal and breast  cancers.

In a new study presented at the annual meeting of the American Society of Clinical Oncology, Indian researchers reported that a cheap, safe, and widely available over-the-counter nonsteroidal anti-inflammatory gel containing 1% diclofenac reduced the incidence of hand-foot syndrome by 75% among patients with cancer being treated with capecitabine.

Up until now, the oral anti-inflammatory celecoxib (Celebrex) was the only agent proven to prevent the problem, but it’s rarely used because of the risk for strokes, gastric bleeding, and other issues, none of which are a concern with topical diclofenac, which osteoarthritis patients have used safely for years.

The Indian trial, dubbed D-Torch, establishes “1% topical diclofenac gel as the new standard of care to prevent capecitabine-associated hand-foot syndrome,” said investigator and study presenter Atul Batra, MD, a medical oncologist at the All India Institute of Medical Sciences, New Delhi.

Dr. Batra told ASCO Daily News that there is no need for a second trial. “We don’t feel there’s a need to replicate these results” in a larger study “because this was adequately powered, and the results speak for themselves. There’s no confusion about these results. Diclofenac is clearly effective.”

Dr. Batra also commented that his clinic now uses topical diclofenac routinely during capecitabine treatment and that he hopes oncology practices elsewhere will do the same.   

Diclofenac gel is sold under the brand name Voltaren and is also available as a generic; in the United States, a 150-gram tube costs about $18 at Walmart.
 

‘The most practice-changing study’ at ASCO 2023

Audience members at ASCO’s annual meeting immediately saw the importance of the study.

Tarah Ballinger, MD, a breast cancer specialist at Indiana University, Indianapolis, said on Twitter that “this might be the most practice changing study I heard at ASCO23.” Topical diclofenac is “widely available, affordable, [and] addresses [a] major” quality of life issue.

The study discussant at the meeting, gastrointestinal cancer specialist Pallavi Kumar, MD, of the University of Pennsylvania, Philadelphia, concurred: “For me as a GI oncologist, topical diclofenac for prevention of HFS for patients on capecitabine is practice changing,” she said.

The takeaway is “that topical diclofenac significantly reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine.” The results are “very impressive,” Dr. Kumar said.

Study details

The idea for the new study came after Batra and colleagues realized that celecoxib, a COX-2 enzyme inhibitor, helps prevent capecitabine hand-foot syndrome (HFS) by blocking a key process that leads to it, the up-regulation of COX-2 and subsequent release of proinflammatory prostaglandins.

They turned to diclofenac gel hoping to get the same effect but more safely; diclofenac is also a COX-2 blocker, and its topical formulation has a strong safety record. 

To test the approach, the team randomly assigned 130 patients to topical diclofenac and 133 to placebo – the gel vehicle without the medication – while they were being treated with capecitabine for 12 weeks; 56% were being treated for breast cancer and the rest for gastrointestinal cancers.

Subjects rubbed one fingertip’s worth of gel – about half a gram – on each palm and the back of each hand twice a day. The dose was about 4 grams/day, which is well below maximal dosages for osteoarthritis (up to 32 g/day over all affected joints). Adherence to treatment was about 95% in both arms.

By the end of 12 weeks, the incidence of grade 2 or higher HFS was 3.8% in the diclofenac arm (5 patients) versus 15% (n = 20) with placebo (P = .003), a 75% risk reduction.

The incidence of any grade HFS was 6.1% in the treatment group versus 18.1% with placebo (P = .003).

Hand-foot syndrome led to dose reductions of capecitabine in 13.5% of placebo but only 3.8% of those in the diclofenac group (P = .002). 

The findings held regardless of whether patients were being treated for breast or GI cancer or if they were men or women. 

Other capecitabine-induced adverse events, including diarrhea, mucositis, and myelosuppression, were not significantly different between the groups.

The treatment arms were well balanced, with a median age of 47 years in both groups and women making up about 70% of each. About 40% of subjects in each group were on capecitabine monotherapy with the rest on combination treatments. The mean dose of capecitabine was just over 1,880 mg/m² in both groups.

At the meeting, Dr. Batra was asked if topical diclofenac would also work for another common problem in oncology: hand-food syndrome occurring as a side-effect with VEGF–tyrosine kinase inhibitors. He didn’t think so because it probably has a different cause than capecitabine HFS, one not strongly related to COX-2 up-regulation.

The study was partly funded by the Indian Supportive Care of Cancer Association. The investigators reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

A version of this article first appeared on Medscape.com.

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

A version of this article first appeared on Medscape.com.

Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.

However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.

These drugs come with a substantial risk of cognitive problems and fatigue and increase the risk of falls by 87%, the authors reported.

These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.

The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.

The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.

Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.

The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.

The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.

The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
 

Study details

The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.

The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).

Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).

The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).

The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.

Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.

The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.

The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors are a cornerstone of non–small cell lung cancer (NSCLC) treatment. But there is a question that’s been vexing oncologists for years: When can treatment be stopped?
 

A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.

“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,”  said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.

“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.

The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.

Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.

In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.

“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
 

Study details

For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.

The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).

Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.

Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.

The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.

Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.

Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.

The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.

There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article first appeared on Medscape.com.

A board-certified New Jersey oncologist has pled guilty to using her medical license to purchase cancer medications under the false pretense that they would be used to treat her own patients, according to a press release from the U.S. Attorney’s Office for the District of New Jersey.

Instead, the drug purchases were part of a fraudulent profit-making scheme.

Anise Kachadourian, MD, of Towaco, N.J. – located about 20 miles from Manhattan – now faces a maximum of 3 years in prison and a $10,000 fine. Her sentencing is scheduled for Feb. 6, 2024.

Overall, “Kachadourian was paid more than $170,000 for purchasing and allowing others to purchase in her name millions of dollars in prescription drugs during the scheme, which ran from October 2016 through January 2019,” the office said in the release.

The scheme involved Dr. Kachadourian and others making “numerous false and misleading representations to the pharmaceutical manufacturers and authorized distributors, including that Dr. Kachadourian purchased the drugs to use to treat her patients, and that the drugs would not be resold or redistributed,” the office said.

However, none of the drugs were administered to any of Dr. Kachadourian’s patients.

The press release explained that while working in her medical practice’s offices in various parts of New Jersey, Dr. Kachadourian was recruited by an individual who owned a pharmacy as well as two wholesale prescription drug distributors.

At this individual’s request and at the request of others who worked for him, Dr. Kachadourian used her medical license and allowed others to use it to purchase expensive drugs. The drugs primarily included cold-chain biologic infusion medications, such as trastuzumab and rituximab, often use to treat cancer, macular degeneration, and autoimmune diseases.

In return, Dr. Kachadourian received a kickback of approximately $5,000 per month.

“By recruiting and using Kachadourian and her medical license to purchase the drugs, these individuals were able to obtain prescription drugs from the pharmaceutical manufacturers’ authorized distributors that they would not otherwise have been permitted to purchase,” the DA’s office said.

The drugs were ultimately sold to customers of the two wholesale distributor businesses “at a significant profit.”

For example, according to a court document, on April 26, 2018, trastuzumab 150 mg was purchased for $254,189.04 and then sold by the wholesale distributor businesses at $336,000, for a profit of $81,810.95.

Dr. Kachadourian is the third doctor to plead guilty to the scheme. The press release didn’t name the other two doctors or the pharmacy owner and their two businesses. A court document did name a coconspirator, Jon Paul Dadaian, MD, a board-certified anesthesiologist and pain management specialist who had offices at several locations in New Jersey.

A version of this article first appeared on Medscape.com.

A board-certified New Jersey oncologist has pled guilty to using her medical license to purchase cancer medications under the false pretense that they would be used to treat her own patients, according to a press release from the U.S. Attorney’s Office for the District of New Jersey.

Instead, the drug purchases were part of a fraudulent profit-making scheme.

Anise Kachadourian, MD, of Towaco, N.J. – located about 20 miles from Manhattan – now faces a maximum of 3 years in prison and a $10,000 fine. Her sentencing is scheduled for Feb. 6, 2024.

Overall, “Kachadourian was paid more than $170,000 for purchasing and allowing others to purchase in her name millions of dollars in prescription drugs during the scheme, which ran from October 2016 through January 2019,” the office said in the release.

The scheme involved Dr. Kachadourian and others making “numerous false and misleading representations to the pharmaceutical manufacturers and authorized distributors, including that Dr. Kachadourian purchased the drugs to use to treat her patients, and that the drugs would not be resold or redistributed,” the office said.

However, none of the drugs were administered to any of Dr. Kachadourian’s patients.

The press release explained that while working in her medical practice’s offices in various parts of New Jersey, Dr. Kachadourian was recruited by an individual who owned a pharmacy as well as two wholesale prescription drug distributors.

At this individual’s request and at the request of others who worked for him, Dr. Kachadourian used her medical license and allowed others to use it to purchase expensive drugs. The drugs primarily included cold-chain biologic infusion medications, such as trastuzumab and rituximab, often use to treat cancer, macular degeneration, and autoimmune diseases.

In return, Dr. Kachadourian received a kickback of approximately $5,000 per month.

“By recruiting and using Kachadourian and her medical license to purchase the drugs, these individuals were able to obtain prescription drugs from the pharmaceutical manufacturers’ authorized distributors that they would not otherwise have been permitted to purchase,” the DA’s office said.

The drugs were ultimately sold to customers of the two wholesale distributor businesses “at a significant profit.”

For example, according to a court document, on April 26, 2018, trastuzumab 150 mg was purchased for $254,189.04 and then sold by the wholesale distributor businesses at $336,000, for a profit of $81,810.95.

Dr. Kachadourian is the third doctor to plead guilty to the scheme. The press release didn’t name the other two doctors or the pharmacy owner and their two businesses. A court document did name a coconspirator, Jon Paul Dadaian, MD, a board-certified anesthesiologist and pain management specialist who had offices at several locations in New Jersey.

A version of this article first appeared on Medscape.com.

A board-certified New Jersey oncologist has pled guilty to using her medical license to purchase cancer medications under the false pretense that they would be used to treat her own patients, according to a press release from the U.S. Attorney’s Office for the District of New Jersey.

Instead, the drug purchases were part of a fraudulent profit-making scheme.

Anise Kachadourian, MD, of Towaco, N.J. – located about 20 miles from Manhattan – now faces a maximum of 3 years in prison and a $10,000 fine. Her sentencing is scheduled for Feb. 6, 2024.

Overall, “Kachadourian was paid more than $170,000 for purchasing and allowing others to purchase in her name millions of dollars in prescription drugs during the scheme, which ran from October 2016 through January 2019,” the office said in the release.

The scheme involved Dr. Kachadourian and others making “numerous false and misleading representations to the pharmaceutical manufacturers and authorized distributors, including that Dr. Kachadourian purchased the drugs to use to treat her patients, and that the drugs would not be resold or redistributed,” the office said.

However, none of the drugs were administered to any of Dr. Kachadourian’s patients.

The press release explained that while working in her medical practice’s offices in various parts of New Jersey, Dr. Kachadourian was recruited by an individual who owned a pharmacy as well as two wholesale prescription drug distributors.

At this individual’s request and at the request of others who worked for him, Dr. Kachadourian used her medical license and allowed others to use it to purchase expensive drugs. The drugs primarily included cold-chain biologic infusion medications, such as trastuzumab and rituximab, often use to treat cancer, macular degeneration, and autoimmune diseases.

In return, Dr. Kachadourian received a kickback of approximately $5,000 per month.

“By recruiting and using Kachadourian and her medical license to purchase the drugs, these individuals were able to obtain prescription drugs from the pharmaceutical manufacturers’ authorized distributors that they would not otherwise have been permitted to purchase,” the DA’s office said.

The drugs were ultimately sold to customers of the two wholesale distributor businesses “at a significant profit.”

For example, according to a court document, on April 26, 2018, trastuzumab 150 mg was purchased for $254,189.04 and then sold by the wholesale distributor businesses at $336,000, for a profit of $81,810.95.

Dr. Kachadourian is the third doctor to plead guilty to the scheme. The press release didn’t name the other two doctors or the pharmacy owner and their two businesses. A court document did name a coconspirator, Jon Paul Dadaian, MD, a board-certified anesthesiologist and pain management specialist who had offices at several locations in New Jersey.

A version of this article first appeared on Medscape.com.

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

A version of this article first appeared on Medscape.com.

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

A version of this article first appeared on Medscape.com.

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

A version of this article first appeared on Medscape.com.