Leukemia, Myelodysplasia, Transplantation

myelodysplastic syndrome

Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.

In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.

Overall survival (OS) was about a year longer for responders than for non-responders.

MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.

Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).

Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.

The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.

Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.

Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).

All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.

Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m²/day to 1700 mg/m²/day in 14-day cycles.

The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m²/day, and the recommended phase 2 dose was 1375 mg/m²/day.

Safety

All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).

The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).

Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.

Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.

Efficacy

Nineteen patients were evaluable for efficacy.

Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.

Five patients had stable disease, 3 with MDS and 2 with tAML.

The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).

“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.

He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.

myelodysplastic syndrome

Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.

In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.

Overall survival (OS) was about a year longer for responders than for non-responders.

MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.

Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).

Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.

The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.

Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.

Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).

All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.

Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m²/day to 1700 mg/m²/day in 14-day cycles.

The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m²/day, and the recommended phase 2 dose was 1375 mg/m²/day.

Safety

All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).

The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).

Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.

Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.

Efficacy

Nineteen patients were evaluable for efficacy.

Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.

Five patients had stable disease, 3 with MDS and 2 with tAML.

The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).

“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.

He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.

myelodysplastic syndrome

Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.

In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.

Overall survival (OS) was about a year longer for responders than for non-responders.

MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.

Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).

Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.

The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.

Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.

Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).

All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.

Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m²/day to 1700 mg/m²/day in 14-day cycles.

The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m²/day, and the recommended phase 2 dose was 1375 mg/m²/day.

Safety

All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).

The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).

Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.

Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.

Efficacy

Nineteen patients were evaluable for efficacy.

Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.

Five patients had stable disease, 3 with MDS and 2 with tAML.

The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).

“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.

He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.

acute lymphoblastic leukemia

The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.

The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.

Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).

acute lymphoblastic leukemia

The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.

The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.

Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).

acute lymphoblastic leukemia

The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.

The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.

Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

acute myeloid leukemia

Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).

The generic drug is approved for the same indications as VIDAZA®.

This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.

It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.

“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.

“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”

VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.

While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.

Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.

Susan London, Frontline Medical News

VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.

While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.

Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.

Susan London, Frontline Medical News

VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.

While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.

Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.

Susan London, Frontline Medical News

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

Photo by Steven Harbour

US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.

A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.

Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.

However, patients who were already paying the most for their medications saw their monthly costs go up.

“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.

“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”

To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.

The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.

About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.

For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).

The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).

“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”

The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).

Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.

For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.

“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.

“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”

However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.

Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.

On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.

The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.

“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”

The Food and Drug Administration has approved dasatinib for children with Philadelphia chromosome–positive (Ph+) chronic phase chronic myeloid leukemia (CML).

The tyrosine kinase inhibitor was approved for the treatment of newly diagnosed adult patients with chronic phase Ph+ CML in 2010.

[email protected]

On Twitter @nikolaideslaura

The Food and Drug Administration has approved dasatinib for children with Philadelphia chromosome–positive (Ph+) chronic phase chronic myeloid leukemia (CML).

The tyrosine kinase inhibitor was approved for the treatment of newly diagnosed adult patients with chronic phase Ph+ CML in 2010.

[email protected]

On Twitter @nikolaideslaura

The Food and Drug Administration has approved dasatinib for children with Philadelphia chromosome–positive (Ph+) chronic phase chronic myeloid leukemia (CML).

The tyrosine kinase inhibitor was approved for the treatment of newly diagnosed adult patients with chronic phase Ph+ CML in 2010.

[email protected]

On Twitter @nikolaideslaura

Among children with average-risk acute lymphoblastic leukemia (ALL), those with impairments in physical and emotional functioning at 2 months after diagnosis are likely to have continuing difficulties over 2 years later, based on the results of a 594-patient study published online in Cancer (2017 Nov 7. doi: 10.1002/cncr.31085).

Evaluations of quality of life and family functioning as early as 2 months after diagnosis identified those at highest risk of continued impairment, and can be used to target patients and their families for interventions and risk factor modification, the researchers said.

“These results provide a compelling rationale to screen patients for physical and emotional functioning early in therapy to target interventions toward patients at the highest risk of later impairment,” wrote lead author Daniel J. Zheng, MD, of the section of pediatric hematology-oncology at Yale University, New Haven, Conn., and coauthors.

Dr. Zheng and his colleagues measured impairments in children with average-risk ALL using the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0), a 23-item survey that measures a child’s quality of life, and the 12-question General Functioning subscale of the McMaster Family Assessment Device (FAD-GF). Both are quick and low-cost screening measures that can be conducted in the clinic, they added. Evaluations occurred at approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis. The mean age of participants at diagnosis was 6.0 years (standard deviation, 1.6 years).

At 2 months after diagnosis, 36.5% of the children had impairments in physical functioning, and 26.2% had impairments in emotional functioning. The population norms for these measures are 2.3% for both scales, investigators wrote. At a 26-month evaluation, levels of impairment were still 11.9% for physical and 9.8% for emotional functioning.

Boys had an additional 38-month evaluation, at which time there were no significant differences in quality of life outcomes versus those observed at 26 months in the girls.

Unhealthy family functioning was a significant predictor of emotional impairment (odds ratio, 1.5; 95% confidence interval, 1.1-2.1) in multivariate models controlling for age and sex.

Strategies are needed to “intervene early and help the substantial proportion of children” with quality of life impairments, the researchers said. In particular, family functioning is “potentially modifiable with early intervention,” as suggested by a series of promising studies of techniques such as stress management sessions for parents. Most techniques feature a “targeted family-centered approach to psychosocial needs” that includes “embedded psychologists” as part of the multidisciplinary cancer care team.

Study funding came from the National Institutes of Health, National Cancer Institute, and the St. Baldrick’s Foundation. Dr. Zheng reported funding from a Yale Medical Student research fellowship, while coauthors reported conflict of interest disclosures from entities including Amgen, Takeda Pharmaceuticals International, and Shire Pharmaceuticals.

Among children with average-risk acute lymphoblastic leukemia (ALL), those with impairments in physical and emotional functioning at 2 months after diagnosis are likely to have continuing difficulties over 2 years later, based on the results of a 594-patient study published online in Cancer (2017 Nov 7. doi: 10.1002/cncr.31085).

Evaluations of quality of life and family functioning as early as 2 months after diagnosis identified those at highest risk of continued impairment, and can be used to target patients and their families for interventions and risk factor modification, the researchers said.

“These results provide a compelling rationale to screen patients for physical and emotional functioning early in therapy to target interventions toward patients at the highest risk of later impairment,” wrote lead author Daniel J. Zheng, MD, of the section of pediatric hematology-oncology at Yale University, New Haven, Conn., and coauthors.

Dr. Zheng and his colleagues measured impairments in children with average-risk ALL using the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0), a 23-item survey that measures a child’s quality of life, and the 12-question General Functioning subscale of the McMaster Family Assessment Device (FAD-GF). Both are quick and low-cost screening measures that can be conducted in the clinic, they added. Evaluations occurred at approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis. The mean age of participants at diagnosis was 6.0 years (standard deviation, 1.6 years).

At 2 months after diagnosis, 36.5% of the children had impairments in physical functioning, and 26.2% had impairments in emotional functioning. The population norms for these measures are 2.3% for both scales, investigators wrote. At a 26-month evaluation, levels of impairment were still 11.9% for physical and 9.8% for emotional functioning.

Boys had an additional 38-month evaluation, at which time there were no significant differences in quality of life outcomes versus those observed at 26 months in the girls.

Unhealthy family functioning was a significant predictor of emotional impairment (odds ratio, 1.5; 95% confidence interval, 1.1-2.1) in multivariate models controlling for age and sex.

Strategies are needed to “intervene early and help the substantial proportion of children” with quality of life impairments, the researchers said. In particular, family functioning is “potentially modifiable with early intervention,” as suggested by a series of promising studies of techniques such as stress management sessions for parents. Most techniques feature a “targeted family-centered approach to psychosocial needs” that includes “embedded psychologists” as part of the multidisciplinary cancer care team.

Study funding came from the National Institutes of Health, National Cancer Institute, and the St. Baldrick’s Foundation. Dr. Zheng reported funding from a Yale Medical Student research fellowship, while coauthors reported conflict of interest disclosures from entities including Amgen, Takeda Pharmaceuticals International, and Shire Pharmaceuticals.

Among children with average-risk acute lymphoblastic leukemia (ALL), those with impairments in physical and emotional functioning at 2 months after diagnosis are likely to have continuing difficulties over 2 years later, based on the results of a 594-patient study published online in Cancer (2017 Nov 7. doi: 10.1002/cncr.31085).

Evaluations of quality of life and family functioning as early as 2 months after diagnosis identified those at highest risk of continued impairment, and can be used to target patients and their families for interventions and risk factor modification, the researchers said.

“These results provide a compelling rationale to screen patients for physical and emotional functioning early in therapy to target interventions toward patients at the highest risk of later impairment,” wrote lead author Daniel J. Zheng, MD, of the section of pediatric hematology-oncology at Yale University, New Haven, Conn., and coauthors.

Dr. Zheng and his colleagues measured impairments in children with average-risk ALL using the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0), a 23-item survey that measures a child’s quality of life, and the 12-question General Functioning subscale of the McMaster Family Assessment Device (FAD-GF). Both are quick and low-cost screening measures that can be conducted in the clinic, they added. Evaluations occurred at approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis. The mean age of participants at diagnosis was 6.0 years (standard deviation, 1.6 years).

At 2 months after diagnosis, 36.5% of the children had impairments in physical functioning, and 26.2% had impairments in emotional functioning. The population norms for these measures are 2.3% for both scales, investigators wrote. At a 26-month evaluation, levels of impairment were still 11.9% for physical and 9.8% for emotional functioning.

Boys had an additional 38-month evaluation, at which time there were no significant differences in quality of life outcomes versus those observed at 26 months in the girls.

Unhealthy family functioning was a significant predictor of emotional impairment (odds ratio, 1.5; 95% confidence interval, 1.1-2.1) in multivariate models controlling for age and sex.

Strategies are needed to “intervene early and help the substantial proportion of children” with quality of life impairments, the researchers said. In particular, family functioning is “potentially modifiable with early intervention,” as suggested by a series of promising studies of techniques such as stress management sessions for parents. Most techniques feature a “targeted family-centered approach to psychosocial needs” that includes “embedded psychologists” as part of the multidisciplinary cancer care team.

Study funding came from the National Institutes of Health, National Cancer Institute, and the St. Baldrick’s Foundation. Dr. Zheng reported funding from a Yale Medical Student research fellowship, while coauthors reported conflict of interest disclosures from entities including Amgen, Takeda Pharmaceuticals International, and Shire Pharmaceuticals.

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel^®).

The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

This approval was granted under priority review, and the drug received orphan designation for this indication.

The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.

The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.

For more details, see the full prescribing information.

Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Pediatric studies

The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.

There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.

Ninety-one patients received dasatinib at 60 mg/m² once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.

The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.

The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).

At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.

At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.

The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.

Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny