Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).

Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).

Photo by Bill Branson

Azacitidine for injection (Vidaza®) is now available in China.

The nucleoside metabolic inhibitor was approved in China to treat patients with intermediate-2/high-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20% to 30% bone marrow blasts, and chronic myelomonocytic leukemia (CMML).

Azacitidine for injection is marketed in China by BeiGene Ltd. under an exclusive license from Celgene Corporation.

“Vidaza is the only approved hypomethylating agent shown to prolong survival for patients with MDS and the first new treatment for MDS patients approved in China since 2009,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene.

“We are excited to announce that the first prescription was made in January 2018. From now on, Chinese patients can benefit from Vidaza in hospitals around China.”

Azacitidine was evaluated in a global phase 3 trial of patients with intermediate-2- and high-risk MDS, CMML, or AML (AZA-001). Results from this trial were published in The Lancet Oncology in 2009.

Patients were randomized to receive azacitidine plus best supportive care (BSC, n=179) or conventional care regimens plus BSC (105 to BSC alone, 49 to low-dose cytarabine, and 25 to chemotherapy with cytarabine and anthracycline).

Azacitidine was given subcutaneously at a dose of 75 mg/m² daily for 7 consecutive days every 28 days until disease progression, relapse after response, or unacceptable toxicity.

The median overall survival was 24.5 months with azacitidine, compared to 15 months for patients treated with conventional care regimens.

There was a higher hematologic response rate in the azacitidine arm than the conventional care arm—29% and 12%, respectively.

In the azacitidine group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent, compared with 11% in the conventional care group.

Forty-six percent of patients in the azacitidine arm and 63% in the conventional care arm died.

Grade 3/4 hematologic toxicity (in the azacitidine and conventional care arms, respectively) included neutropenia (91% and 76%), thrombocytopenia (85% and 80%), and anemia (57% and 68%).

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

SAN FRANCISCO – Patients who have undergone nephro-ureterectomy for upper-tract urothelial cancer (UTUC) fare much better if they are given adjuvant chemotherapy, according to the first results of the POUT trial reported at the 2018 Genitourinary Cancers Symposium.

Standard treatment for this rare cancer is radical nephro-ureterectomy followed by surveillance, noted lead author Alison Jane Birtle, MD, MRCP, FRCR, a consultant clinical oncologist at the Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom. Evidence has been insufficient to recommend adjuvant therapy.

“We know that UTUC shares a similar etiology with bladder cancer, where there is strong evidence for chemotherapy,” she said. “Trials of adjuvant chemotherapy in bladder cancer have been challenging because of cystectomy being a much more morbid operation. So adjuvant chemotherapy after nephro-ureterectomy should be much easier to give because of the less morbid procedure.”

Other viewpoints

“It’s fantastic that we finally have data in upper-tract cancer. However, I worry about how this data is going to be interpreted, and I argue that it should not be considered the standard of care,” session attendee Matthew Campbell, MD, of the MD Anderson Cancer Center, Houston, commented during a question and answer period.

“I believe that this is showing that chemotherapy is very important in this disease, and if anything, it should be moved into the neoadjuvant setting, where more patients will be cisplatin candidates. Though there is challenge with staging upper-tract disease, at MD Anderson, we consider patients with high-grade disease or hydronephrosis to be at high enough risk to consider for neoadjuvant chemotherapy, and that’s been our approach.”

“When we looked at developing POUT, there was a big debate about whether it should be a neoadjuvant or adjuvant study,” Dr. Birtle replied. UK oncologists expressed concern that not all patients have histologic confirmation of UTUC preoperatively; therefore, chemotherapy could lead to overtreatment for some.

“We plan to go back and look at the CT urograms and the diagnostic imaging done prior to surgery just to see if we can be 100% confident in our diagnostic accuracy preoperatively, to see if we would be more confident with a neoadjuvant study,” she added. The investigators have also reviewed data from the British Association of Urological Surgeons on the postoperative dip in GFR. “It didn’t really seem from that 2015 data that there was a huge unmet need for patients postoperatively, where we would have missed them had we not treated them preoperatively,” she said.

On a related note, session attendee Surena Matin, MD, also of MD Anderson, asked “How many patients were potentially precluded because of their GFR, and do you have any data regarding response rates in the carboplatin arm?”

The main reason for exclusion was ineligible pathology and not GFR, according to Dr. Birtle. “This goes back to the previous question of can you be certain that a patient has locally advanced disease prior to nephro-ureterectomy? About 60% of patients who were thought to have muscle-invasive disease ultimately on nephro-ureterectomy didn’t.”

Confidence intervals for chemotherapy benefit in the subgroup given carboplatin were wide and overlapped unity, but still favoring benefit and falling within the overall treatment effect, she said.

Session attendee Joaquim Bellmunt, MD, Dana-Farber Cancer Institute, Boston, noted that the chemotherapy benefit was not significant in that subgroup and also in the subgroups with lymph node–positive disease and with positive margins. “I think that saying … chemotherapy is for everybody based on this trial” is incorrect, he asserted. “It may be good just to tone down the message that this is the new standard of care.” He further questioned the trial’s early stopping, noting that continuing would have provided more information in these patients.

Those subgroups were small, so analyses were underpowered to definitively rule out chemotherapy benefit, according to Dr. Birtle. The investigators had intensive discussion about the recommendation to stop early, because of a goal to determine overall survival impact. Ultimately, “when we saw the data in terms of disease-free survival and metastasis-free survival, the magnitude of the effect was so big that we felt it was uncomfortable and unethical not to offer patients treatment,” she said.

Study details

Patients in POUT’s chemotherapy arm received four cycles of chemotherapy—gemcitabine-cisplatin if their GFR was 50 mL/min or higher, or gemcitabine-carboplatin if their GFR was 30-49 mL/min—starting within 90 days of nephro-ureterectomy.

Of note, approximately 40% of all patients in the trial were aged 70 years or older, including the 5% who were aged 80 years or older. “This is very reassuring for a study of adjuvant platinum-based chemotherapy,” Dr. Birtle commented. Fully 71.2% of the chemotherapy patients received all four planned cycles.

In an intention-to-treat analysis, risk of disease-free survival events (death from any cause, metastasis, or any ureteric or renal bed recurrence) was sharply reduced with chemotherapy versus surveillance (hazard ratio, 0.49; P=.001). The proportion of patients event free at 2 years was 71% in the chemotherapy group and 54% in the surveillance group. Benefit was generally similar across subgroups, and findings were much the same after adjustment for nodal involvement, microscopic margin status, and planned chemotherapy regimen (hazard ratio, 0.47; P=.001).

Risk of metastasis-free survival events was also sharply lower with chemotherapy (hazard ratio, 0.49; P=.002), with a proportion event free at 2 years of 74% in the chemotherapy group and 60% in the surveillance group. These findings were also much the same after adjustment for the above factors (hazard ratio, 0.47; P=.002).

Overall survival tended to be better with chemotherapy than with surveillance (hazard ratio, 0.55), but data are still immature for this endpoint.

The rate of grade 3 or worse adverse events during the treatment period was 53.2% with chemotherapy and 13.5% with surveillance; events with chemotherapy were as expected, with neutropenia, thrombocytopenia, and gastrointestinal events predominating. The rate of febrile neutropenia was 5.7% with gemcitabine-cisplatin and 7.8% with gemcitabine-carboplatin, but there were no neutropenic deaths.

The rate of grade 3 or worse adverse events for the entire trial period was 62.1% with chemotherapy and 24.8% with surveillance.

Data on nephrotoxicity are still being evaluated, according to Dr. Birtle. Only seven patients who started on gemcitabine-cisplatin had to switch to gemcitabine-carboplatin because their GFR fell.

In a related translational study, the investigators are evaluating both the baseline CT urograms and the resected tumors to identify prognostic and predictive markers, she said.

Dr. Birtle disclosed that she receives honoraria from Roche, Janssen, Astellas, and Bayer, and is a consultant to Sanofi-Aventis. The trial was funded by the UK Clinical Trials Awards and Advisory Committee.

SOURCE: Birtle A et al. Genitourinary Cancers Symposium. Abstract 407

SAN FRANCISCO – Patients who have undergone nephro-ureterectomy for upper-tract urothelial cancer (UTUC) fare much better if they are given adjuvant chemotherapy, according to the first results of the POUT trial reported at the 2018 Genitourinary Cancers Symposium.

Standard treatment for this rare cancer is radical nephro-ureterectomy followed by surveillance, noted lead author Alison Jane Birtle, MD, MRCP, FRCR, a consultant clinical oncologist at the Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom. Evidence has been insufficient to recommend adjuvant therapy.

“We know that UTUC shares a similar etiology with bladder cancer, where there is strong evidence for chemotherapy,” she said. “Trials of adjuvant chemotherapy in bladder cancer have been challenging because of cystectomy being a much more morbid operation. So adjuvant chemotherapy after nephro-ureterectomy should be much easier to give because of the less morbid procedure.”

Other viewpoints

“It’s fantastic that we finally have data in upper-tract cancer. However, I worry about how this data is going to be interpreted, and I argue that it should not be considered the standard of care,” session attendee Matthew Campbell, MD, of the MD Anderson Cancer Center, Houston, commented during a question and answer period.

“I believe that this is showing that chemotherapy is very important in this disease, and if anything, it should be moved into the neoadjuvant setting, where more patients will be cisplatin candidates. Though there is challenge with staging upper-tract disease, at MD Anderson, we consider patients with high-grade disease or hydronephrosis to be at high enough risk to consider for neoadjuvant chemotherapy, and that’s been our approach.”

“When we looked at developing POUT, there was a big debate about whether it should be a neoadjuvant or adjuvant study,” Dr. Birtle replied. UK oncologists expressed concern that not all patients have histologic confirmation of UTUC preoperatively; therefore, chemotherapy could lead to overtreatment for some.

“We plan to go back and look at the CT urograms and the diagnostic imaging done prior to surgery just to see if we can be 100% confident in our diagnostic accuracy preoperatively, to see if we would be more confident with a neoadjuvant study,” she added. The investigators have also reviewed data from the British Association of Urological Surgeons on the postoperative dip in GFR. “It didn’t really seem from that 2015 data that there was a huge unmet need for patients postoperatively, where we would have missed them had we not treated them preoperatively,” she said.

On a related note, session attendee Surena Matin, MD, also of MD Anderson, asked “How many patients were potentially precluded because of their GFR, and do you have any data regarding response rates in the carboplatin arm?”

The main reason for exclusion was ineligible pathology and not GFR, according to Dr. Birtle. “This goes back to the previous question of can you be certain that a patient has locally advanced disease prior to nephro-ureterectomy? About 60% of patients who were thought to have muscle-invasive disease ultimately on nephro-ureterectomy didn’t.”

Confidence intervals for chemotherapy benefit in the subgroup given carboplatin were wide and overlapped unity, but still favoring benefit and falling within the overall treatment effect, she said.

Session attendee Joaquim Bellmunt, MD, Dana-Farber Cancer Institute, Boston, noted that the chemotherapy benefit was not significant in that subgroup and also in the subgroups with lymph node–positive disease and with positive margins. “I think that saying … chemotherapy is for everybody based on this trial” is incorrect, he asserted. “It may be good just to tone down the message that this is the new standard of care.” He further questioned the trial’s early stopping, noting that continuing would have provided more information in these patients.

Those subgroups were small, so analyses were underpowered to definitively rule out chemotherapy benefit, according to Dr. Birtle. The investigators had intensive discussion about the recommendation to stop early, because of a goal to determine overall survival impact. Ultimately, “when we saw the data in terms of disease-free survival and metastasis-free survival, the magnitude of the effect was so big that we felt it was uncomfortable and unethical not to offer patients treatment,” she said.

Study details

Patients in POUT’s chemotherapy arm received four cycles of chemotherapy—gemcitabine-cisplatin if their GFR was 50 mL/min or higher, or gemcitabine-carboplatin if their GFR was 30-49 mL/min—starting within 90 days of nephro-ureterectomy.

Of note, approximately 40% of all patients in the trial were aged 70 years or older, including the 5% who were aged 80 years or older. “This is very reassuring for a study of adjuvant platinum-based chemotherapy,” Dr. Birtle commented. Fully 71.2% of the chemotherapy patients received all four planned cycles.

In an intention-to-treat analysis, risk of disease-free survival events (death from any cause, metastasis, or any ureteric or renal bed recurrence) was sharply reduced with chemotherapy versus surveillance (hazard ratio, 0.49; P=.001). The proportion of patients event free at 2 years was 71% in the chemotherapy group and 54% in the surveillance group. Benefit was generally similar across subgroups, and findings were much the same after adjustment for nodal involvement, microscopic margin status, and planned chemotherapy regimen (hazard ratio, 0.47; P=.001).

Risk of metastasis-free survival events was also sharply lower with chemotherapy (hazard ratio, 0.49; P=.002), with a proportion event free at 2 years of 74% in the chemotherapy group and 60% in the surveillance group. These findings were also much the same after adjustment for the above factors (hazard ratio, 0.47; P=.002).

Overall survival tended to be better with chemotherapy than with surveillance (hazard ratio, 0.55), but data are still immature for this endpoint.

The rate of grade 3 or worse adverse events during the treatment period was 53.2% with chemotherapy and 13.5% with surveillance; events with chemotherapy were as expected, with neutropenia, thrombocytopenia, and gastrointestinal events predominating. The rate of febrile neutropenia was 5.7% with gemcitabine-cisplatin and 7.8% with gemcitabine-carboplatin, but there were no neutropenic deaths.

The rate of grade 3 or worse adverse events for the entire trial period was 62.1% with chemotherapy and 24.8% with surveillance.

Data on nephrotoxicity are still being evaluated, according to Dr. Birtle. Only seven patients who started on gemcitabine-cisplatin had to switch to gemcitabine-carboplatin because their GFR fell.

In a related translational study, the investigators are evaluating both the baseline CT urograms and the resected tumors to identify prognostic and predictive markers, she said.

Dr. Birtle disclosed that she receives honoraria from Roche, Janssen, Astellas, and Bayer, and is a consultant to Sanofi-Aventis. The trial was funded by the UK Clinical Trials Awards and Advisory Committee.

SOURCE: Birtle A et al. Genitourinary Cancers Symposium. Abstract 407

SAN FRANCISCO – Patients who have undergone nephro-ureterectomy for upper-tract urothelial cancer (UTUC) fare much better if they are given adjuvant chemotherapy, according to the first results of the POUT trial reported at the 2018 Genitourinary Cancers Symposium.

Standard treatment for this rare cancer is radical nephro-ureterectomy followed by surveillance, noted lead author Alison Jane Birtle, MD, MRCP, FRCR, a consultant clinical oncologist at the Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom. Evidence has been insufficient to recommend adjuvant therapy.

“We know that UTUC shares a similar etiology with bladder cancer, where there is strong evidence for chemotherapy,” she said. “Trials of adjuvant chemotherapy in bladder cancer have been challenging because of cystectomy being a much more morbid operation. So adjuvant chemotherapy after nephro-ureterectomy should be much easier to give because of the less morbid procedure.”

Other viewpoints

“It’s fantastic that we finally have data in upper-tract cancer. However, I worry about how this data is going to be interpreted, and I argue that it should not be considered the standard of care,” session attendee Matthew Campbell, MD, of the MD Anderson Cancer Center, Houston, commented during a question and answer period.

“I believe that this is showing that chemotherapy is very important in this disease, and if anything, it should be moved into the neoadjuvant setting, where more patients will be cisplatin candidates. Though there is challenge with staging upper-tract disease, at MD Anderson, we consider patients with high-grade disease or hydronephrosis to be at high enough risk to consider for neoadjuvant chemotherapy, and that’s been our approach.”

“When we looked at developing POUT, there was a big debate about whether it should be a neoadjuvant or adjuvant study,” Dr. Birtle replied. UK oncologists expressed concern that not all patients have histologic confirmation of UTUC preoperatively; therefore, chemotherapy could lead to overtreatment for some.

“We plan to go back and look at the CT urograms and the diagnostic imaging done prior to surgery just to see if we can be 100% confident in our diagnostic accuracy preoperatively, to see if we would be more confident with a neoadjuvant study,” she added. The investigators have also reviewed data from the British Association of Urological Surgeons on the postoperative dip in GFR. “It didn’t really seem from that 2015 data that there was a huge unmet need for patients postoperatively, where we would have missed them had we not treated them preoperatively,” she said.

On a related note, session attendee Surena Matin, MD, also of MD Anderson, asked “How many patients were potentially precluded because of their GFR, and do you have any data regarding response rates in the carboplatin arm?”

The main reason for exclusion was ineligible pathology and not GFR, according to Dr. Birtle. “This goes back to the previous question of can you be certain that a patient has locally advanced disease prior to nephro-ureterectomy? About 60% of patients who were thought to have muscle-invasive disease ultimately on nephro-ureterectomy didn’t.”

Confidence intervals for chemotherapy benefit in the subgroup given carboplatin were wide and overlapped unity, but still favoring benefit and falling within the overall treatment effect, she said.

Session attendee Joaquim Bellmunt, MD, Dana-Farber Cancer Institute, Boston, noted that the chemotherapy benefit was not significant in that subgroup and also in the subgroups with lymph node–positive disease and with positive margins. “I think that saying … chemotherapy is for everybody based on this trial” is incorrect, he asserted. “It may be good just to tone down the message that this is the new standard of care.” He further questioned the trial’s early stopping, noting that continuing would have provided more information in these patients.

Those subgroups were small, so analyses were underpowered to definitively rule out chemotherapy benefit, according to Dr. Birtle. The investigators had intensive discussion about the recommendation to stop early, because of a goal to determine overall survival impact. Ultimately, “when we saw the data in terms of disease-free survival and metastasis-free survival, the magnitude of the effect was so big that we felt it was uncomfortable and unethical not to offer patients treatment,” she said.

Study details

Patients in POUT’s chemotherapy arm received four cycles of chemotherapy—gemcitabine-cisplatin if their GFR was 50 mL/min or higher, or gemcitabine-carboplatin if their GFR was 30-49 mL/min—starting within 90 days of nephro-ureterectomy.

Of note, approximately 40% of all patients in the trial were aged 70 years or older, including the 5% who were aged 80 years or older. “This is very reassuring for a study of adjuvant platinum-based chemotherapy,” Dr. Birtle commented. Fully 71.2% of the chemotherapy patients received all four planned cycles.

In an intention-to-treat analysis, risk of disease-free survival events (death from any cause, metastasis, or any ureteric or renal bed recurrence) was sharply reduced with chemotherapy versus surveillance (hazard ratio, 0.49; P=.001). The proportion of patients event free at 2 years was 71% in the chemotherapy group and 54% in the surveillance group. Benefit was generally similar across subgroups, and findings were much the same after adjustment for nodal involvement, microscopic margin status, and planned chemotherapy regimen (hazard ratio, 0.47; P=.001).

Risk of metastasis-free survival events was also sharply lower with chemotherapy (hazard ratio, 0.49; P=.002), with a proportion event free at 2 years of 74% in the chemotherapy group and 60% in the surveillance group. These findings were also much the same after adjustment for the above factors (hazard ratio, 0.47; P=.002).

Overall survival tended to be better with chemotherapy than with surveillance (hazard ratio, 0.55), but data are still immature for this endpoint.

The rate of grade 3 or worse adverse events during the treatment period was 53.2% with chemotherapy and 13.5% with surveillance; events with chemotherapy were as expected, with neutropenia, thrombocytopenia, and gastrointestinal events predominating. The rate of febrile neutropenia was 5.7% with gemcitabine-cisplatin and 7.8% with gemcitabine-carboplatin, but there were no neutropenic deaths.

The rate of grade 3 or worse adverse events for the entire trial period was 62.1% with chemotherapy and 24.8% with surveillance.

Data on nephrotoxicity are still being evaluated, according to Dr. Birtle. Only seven patients who started on gemcitabine-cisplatin had to switch to gemcitabine-carboplatin because their GFR fell.

In a related translational study, the investigators are evaluating both the baseline CT urograms and the resected tumors to identify prognostic and predictive markers, she said.

Dr. Birtle disclosed that she receives honoraria from Roche, Janssen, Astellas, and Bayer, and is a consultant to Sanofi-Aventis. The trial was funded by the UK Clinical Trials Awards and Advisory Committee.

SOURCE: Birtle A et al. Genitourinary Cancers Symposium. Abstract 407

DALLAS – A hospital-wide intervention designed to prevent stillbirth by focusing on reduced fetal movement failed to do so – but did result in significant increases in labor induction and cesarean sections.

After the interventions was implemented, hospitals achieved a stillbirth rate of 4 per 1,000 – not significantly different than the 4.4 per 1,000 rate in the controls, Jane Norman, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine. On the other hand, the risk of a C-section increased by 9% and the risk of a labor induction by 8%, said Prof. Norman of the University of Edinburgh.

Michele G Sullivan/Frontline Medical News

[email protected]

SOURCE: Norman JE et al. Am J Obstet Gynecol. 2018;218,S603.

DALLAS – A hospital-wide intervention designed to prevent stillbirth by focusing on reduced fetal movement failed to do so – but did result in significant increases in labor induction and cesarean sections.

After the interventions was implemented, hospitals achieved a stillbirth rate of 4 per 1,000 – not significantly different than the 4.4 per 1,000 rate in the controls, Jane Norman, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine. On the other hand, the risk of a C-section increased by 9% and the risk of a labor induction by 8%, said Prof. Norman of the University of Edinburgh.

Michele G Sullivan/Frontline Medical News

[email protected]

SOURCE: Norman JE et al. Am J Obstet Gynecol. 2018;218,S603.

DALLAS – A hospital-wide intervention designed to prevent stillbirth by focusing on reduced fetal movement failed to do so – but did result in significant increases in labor induction and cesarean sections.

After the interventions was implemented, hospitals achieved a stillbirth rate of 4 per 1,000 – not significantly different than the 4.4 per 1,000 rate in the controls, Jane Norman, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine. On the other hand, the risk of a C-section increased by 9% and the risk of a labor induction by 8%, said Prof. Norman of the University of Edinburgh.

Michele G Sullivan/Frontline Medical News

[email protected]

SOURCE: Norman JE et al. Am J Obstet Gynecol. 2018;218,S603.

The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.

“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and as the United States is on the verge of a similar transition, the ACR is poised to reconsider its position” on biosimilars, S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.

The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.

The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.

“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.

EULAR2017 - Streaming.hr

Immunogenicity

Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”

Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
 

Extrapolation of indications

The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.

However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
 

Substitution, interchangeability, and switching

The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.

While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.

Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.

While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.

“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
 

Costs

The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.

“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”

It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.

No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.

[email protected]

SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402

The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.

“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and as the United States is on the verge of a similar transition, the ACR is poised to reconsider its position” on biosimilars, S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.

The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.

The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.

“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.

EULAR2017 - Streaming.hr

Immunogenicity

Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”

Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
 

Extrapolation of indications

The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.

However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
 

Substitution, interchangeability, and switching

The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.

While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.

Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.

While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.

“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
 

Costs

The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.

“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”

It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.

No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.

[email protected]

SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402

The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.

“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and as the United States is on the verge of a similar transition, the ACR is poised to reconsider its position” on biosimilars, S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.

The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.

The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.

“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.

EULAR2017 - Streaming.hr

Immunogenicity

Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”

Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
 

Extrapolation of indications

The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.

However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
 

Substitution, interchangeability, and switching

The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.

While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.

Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.

While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.

“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
 

Costs

The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.

“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”

It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.

No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.

[email protected]

SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402

KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.

It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.

Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.

It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.

Dr. Eichenfield explained how the field is evolving and discussed the pediatric experience with dupilumab to date, in addition to how he is using crisaborole (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.

Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.

It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.

Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.

It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.

Dr. Eichenfield explained how the field is evolving and discussed the pediatric experience with dupilumab to date, in addition to how he is using crisaborole (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.

Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

KAUAI, HAWAII – Pediatric dermatologists aren’t waiting for Food and Drug Administration approval to try dupilumab (Dupixent) for their patients with severe atopic dermatitis.

It’s not approved in children, but the possibility of good control without the side effects of cyclosporine and other alternatives is too much to resist. A phase 2, company-sponsored study reported Eczema Area and Severity Index score improvements of up to 76% in pediatric patients treated with dupilumab, an interleukin-4 and IL-13 signaling blocker approved in 2017 for moderate to severe AD in adults.

Large pediatric trials are pending, but with results like that, “many of us just feel if it was our own kid, and we could get dupilumab, we would like to do that first,” said Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego.

It’s not just dupilumab that’s causing excitement. With almost 20 biologics in the pipeline, eczema seems poised to undergo a revolution in treatment much like psoriasis has in recent years.

Dr. Eichenfield explained how the field is evolving and discussed the pediatric experience with dupilumab to date, in addition to how he is using crisaborole (Eucrisa), a topical nonsteroidal phosphodiesterase-4 inhibitor approved for mild to moderate AD for children and adults ages two and older in December 2016, which doesn’t seem to have the duration limits of steroids, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Treatment of pediatric AD is “going to be a very different picture over the next few years,” he said.

Dr. Eichenfield is a consultant or investigator for many companies, including Regeneron/Sanofi, Genentech, Novartis, Pfizer, Lilly, and Allergan.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.

Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.

Clinical implications

“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”

Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”

“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
 

Study details

The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.

Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.

Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.

“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.

“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”

In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group

Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).

Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.

When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.

Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.

[email protected]

SOURCE: James ND et al. GUCS Abstract 162.

SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.

Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.

Clinical implications

“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”

Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”

“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
 

Study details

The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.

Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.

Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.

“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.

“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”

In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group

Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).

Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.

When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.

Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.

[email protected]

SOURCE: James ND et al. GUCS Abstract 162.

SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.

Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.

Clinical implications

“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”

Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”

“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.
 

Study details

The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.

Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.

Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.

“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.

“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”

In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group

Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).

Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.

When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.

Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.

[email protected]

SOURCE: James ND et al. GUCS Abstract 162.

Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.

Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.

New EAA Members

Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.

Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series. The series highlights unique case studies and the important role the VA plays in graduate medical education. Dr. Breu is an assistant professor of medicine at Harvard Medical School and the director of resident education at the VA Boston Healthcare System.

Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.

Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.

William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.

Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the Veteran and Military Care Academic Programs at the University of Colorado College of Nursing, which trains health care providers to address the unique needs of both veteran and active-duty populations.

Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.

Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.

Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.

New EAA Members

Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.

Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series. The series highlights unique case studies and the important role the VA plays in graduate medical education. Dr. Breu is an assistant professor of medicine at Harvard Medical School and the director of resident education at the VA Boston Healthcare System.

Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.

Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.

William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.

Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the Veteran and Military Care Academic Programs at the University of Colorado College of Nursing, which trains health care providers to address the unique needs of both veteran and active-duty populations.

Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.

Being a peer-reviewed journal, Federal Practitioner relies on the dedicated efforts of a great number of unsung (and uncompensated) people, and we would like to recognize these efforts. This journal exists because of the large body of federal health care providers who devote their time and energy to sharing best practices, case studies, literature reviews, and original research. An even larger number of men and women review the many submissions, check the research, and provide essential feedback to our authors. By design, this army of reviewers remains anonymous, but that does not diminish their importance.

Although it would be impossible to adequately thank our reviewers, authors, and other contributors, sufficiently, we are trying. We are delighted to induct some of the most engaged members of the Federal Practitioner community to the Editorial Advisory Association (EAA). The EAA helps guide the journal to ensure it remains focused on the essential issues that confront federal health care providers. Federal Practitioner strives for continuous improvement and is focused on enhancing the breadth, depth, and quality of the online and print content. The EAA plays an important role in that process, and we thank all the current EAA and new members for their guidance.

New EAA Members

Susanne G. Barnett, PharmD, BCPS, has directed the Pharmacy Notes column for Federal Practitioner since 2015. Dr. Barnett is an associate professor at the University of Wisconsin-Madison School of Pharmacy and a clinical pharmacist at the William S. Middleton Memorial Veterans Hospital. She has focused on antimicrobial stewardship and infectious diseases.

Anthony Breu, MD, conceived and directs the VA Boston Medical Forum series. The series highlights unique case studies and the important role the VA plays in graduate medical education. Dr. Breu is an assistant professor of medicine at Harvard Medical School and the director of resident education at the VA Boston Healthcare System.

Maggie Chartier, PsyD, MPH, has authored multiple articles for Federal Practitioner and provided guidance and direction for the 2017 and (forthcoming) 2018 editions of the public pathogens/infectious diseases special issues. Dr. Chartier is the deputy director for the HIV, Hepatitis, and Related Conditions Program in the VHA Office of Specialty Care Services and an assistant clinical professor at the University of California, San Francisco.

Marcia Johnson, DNP, FNP-BC, has been a highly active author and peer reviewer. Dr. Johnson has been a nurse practitioner at the VA for 18 years, and currently provides primary care at the Clermont CBOC in Florida. She previously served as the hepatitis C research coordinator at Philadelphia VAMC and practiced at the Orlando VAMC spinal cord injury clinic.

William Rodríguez-Cintrón, MD, is another active peer reviewer and a prolific contributor. Dr. Rodríguez-Cintrón is chief of the pulmonary, critical care and sleep medicine departments at the VA Caribbean Healthcare System in Puerto Rico.

Col. (Ret) Mona Pearl Treyball, PhD, MS, RN, USAF, also has been a dedicated peer reviewer. Col. Treyball is professor and specialty director of the Veteran and Military Care Academic Programs at the University of Colorado College of Nursing, which trains health care providers to address the unique needs of both veteran and active-duty populations.

Federal Practitioner would like to thank all of the current and new members of the EAA for their continued support. All of the journal’s successes are built on their dedication and commitment. Federal Practitioner encourages all the members of the federal health care community to become more involved, whether as a peer reviewer, author, or by responding to our content in print, online, or via social media. Your feedback and involvement makes this journal better.

The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).

The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.

[email protected]

The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).

The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.

[email protected]

The Food and Drug Administration has approved abiraterone acetate tablets in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer (CSPC).

The FDA first approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who had received prior chemotherapy. The indication was expanded in 2012 to patients with metastatic castration-resistant prostate cancer, the FDA said in a press statement.

[email protected]

Mother has severe pain — uterine rupture: $9M settlement

At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous cesarean delivery. When seen by hospital nurses, she was dilated to .5-cm and reported a pain score of 8/10. Fetal heart-rate (FHR) monitoring showed that the mother was having irregular contractions and that the baby had a reassuring heart-rate tracing. Her ObGyn, contacted by phone, prescribed a medication to stop the contractions. The patient’s pain score dropped to 0/10, and she was discharged.

She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00 am. The ObGyn ordered a cesarean delivery via phone at 8:05 am, and said he was leaving for the hospital. An on-call ObGyn began the cesarean delivery at 8:52 am and found a uterine rupture with the baby outside the uterus. The patient’s ObGyn arrived just after the incision was made. The infant was delivered at 8:54 am.

The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.

The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.

PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.

VERDICT: A $9 million Michigan settlement was reached during mediation.

Baby dies at birth: $1.3M settlement

A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.

PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.

PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.

VERDICT: A $1.3 million Virginia settlement was reached.

Was tachycardic FHR ignored? $3M settlement

A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.

After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.

DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.

VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Mother has severe pain — uterine rupture: $9M settlement

At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous cesarean delivery. When seen by hospital nurses, she was dilated to .5-cm and reported a pain score of 8/10. Fetal heart-rate (FHR) monitoring showed that the mother was having irregular contractions and that the baby had a reassuring heart-rate tracing. Her ObGyn, contacted by phone, prescribed a medication to stop the contractions. The patient’s pain score dropped to 0/10, and she was discharged.

She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00 am. The ObGyn ordered a cesarean delivery via phone at 8:05 am, and said he was leaving for the hospital. An on-call ObGyn began the cesarean delivery at 8:52 am and found a uterine rupture with the baby outside the uterus. The patient’s ObGyn arrived just after the incision was made. The infant was delivered at 8:54 am.

The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.

The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.

PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.

VERDICT: A $9 million Michigan settlement was reached during mediation.

Baby dies at birth: $1.3M settlement

A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.

PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.

PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.

VERDICT: A $1.3 million Virginia settlement was reached.

Was tachycardic FHR ignored? $3M settlement

A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.

After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.

DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.

VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Mother has severe pain — uterine rupture: $9M settlement

At 37 weeks’ gestation, a woman went to the hospital with contractions and abdominal pain 2 weeks before her scheduled delivery. She had a previous cesarean delivery. When seen by hospital nurses, she was dilated to .5-cm and reported a pain score of 8/10. Fetal heart-rate (FHR) monitoring showed that the mother was having irregular contractions and that the baby had a reassuring heart-rate tracing. Her ObGyn, contacted by phone, prescribed a medication to stop the contractions. The patient’s pain score dropped to 0/10, and she was discharged.

She returned the next night after midnight with contractions and a pain score of 9/10, and she was admitted. The nurses spoke with the ObGyn via phone 6 times over the next 8 hours. He prescribed 3 pain medications but the patient’s pain was unresponsive. When the patient called her ObGyn, he told her an ultrasound would be performed and the baby would be delivered in the morning. FHR monitoring became nonreassuring at 8:00 am. The ObGyn ordered a cesarean delivery via phone at 8:05 am, and said he was leaving for the hospital. An on-call ObGyn began the cesarean delivery at 8:52 am and found a uterine rupture with the baby outside the uterus. The patient’s ObGyn arrived just after the incision was made. The infant was delivered at 8:54 am.

The baby was transferred to the neonatal intensive care unit (NICU) where he received therapeutic hypothermia. The parents were told that there was a 70% chance that the child would have cerebral palsy. The baby required a feeding tube and was hospitalized for 84 days. After discharge, he was moved to a long-term care facility. During his first year of life, he had pneumonia requiring hospitalization. Due to frequent aspiration of food and saliva into his airway, a tracheostomy was placed.

The child has hypoxic ischemic encephalopathy with severe brain damage, including spastic quadriplegic cerebral palsy. He is blind but can hear. He will need 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The ObGyn did not properly react to the mother’s reported severe pain. A cesarean delivery should have been performed when the mother first reported to the hospital or when she returned the following night.

PHYSICIAN'S DEFENSE: The defense was expected to argue at trial that the mother was not in labor because medication had stopped contractions; therefore it was reasonable to mature longer before delivery. The case settled during the trial.

VERDICT: A $9 million Michigan settlement was reached during mediation.

Baby dies at birth: $1.3M settlement

A 39-year-old woman was admitted to the hospital at 36 weeks’ gestation with regular contractions. Results of an ultrasound showed normal amniotic fluid and an anterior placental location. The patient’s membranes were artificially ruptured, and she received an epidural. The baby remained at plus-one station for more than 7 hours until delivery. Three attempts to rotate the baby over the course of labor failed. Variable decelerations were present on FHR monitoring throughout labor, and deep decelerations were noted within 2 hours of delivery. The ObGyn ordered cesarean delivery due to arrest of labor and fetal distress; delivery began 64 minutes after the decision. The baby’s head was deeply impacted in the pelvis and a Bandl’s ring was encountered. Several attempts were made to dislodge the fetal head. The fourth attempt, in conjunction with enlarging the hysterotomy, was successful. At birth, the baby was pale with no palpable pulse. A 17-minute resuscitation effort failed. An autopsy concluded that the cause of death was a subgaleal hemorrhage in the setting of acute and subacute placental pathology.

PARENT'S CLAIM: The ObGyn was negligent for not performing a cesarean delivery when the baby could not be rotated from a plus-one station and fetal distress was evident. The ObGyn never accessed the patient’s electronic medical records during the 8 hours of labor. An audit trail review revealed the editing and alleged purging of medical records.

PHYSICIAN'S CLAIM: The case was defended on the basis of the autopsy findings, alleging that the baby was compromised before labor and delivery. A pathology expert testified that blood loss from a subgaleal hemorrhage was not necessarily lethal and may occur spontaneously. However, the pathologist conceded that she failed to note complications that occurred during delivery and acknowledged that the autopsy did not document the bruising of the baby’s head, ear, neck, shoulder, and torso that was evident in autopsy photographs.

VERDICT: A $1.3 million Virginia settlement was reached.

Was tachycardic FHR ignored? $3M settlement

A 25-year-old woman with gestational diabetes was scheduled for induction of labor at 39 2/7 weeks’ gestation. When she presented for induction, artificial rupture of the membranes demonstrated clear fluid with no sign of fetal or maternal distress. Labor and delivery was managed by a certified nurse midwife (CNM) employed by an ObGyn group. Just prior to the CNM’s arrival, the FHR monitor tracings showed a series of decelerations; the CNM stopped the oxytocin. As labor progressed, the CNM reintroduced and increased the oxytocin dosage. The infant’s heart rate became tachycardic. The CNM documented a bloody show of vaginal fluid. After the mother began pushing, the FHR signal was lost on the external monitor and only the maternal pulse was detected. As the infant’s head crowned, the FHR monitor was reconnected; an FHR of 210 bpm was detected showing marked tachycardia.

After vaginal delivery, the child was limp and unresponsive. He had hypoxic ischemic encephalopathy and immediately began to have seizures. He was transferred to the NICU at another hospital where he stayed for 34 days. The infant was found to have spastic quadriplegic cerebral palsy, cortical visual impairment, a seizure disorder, right-sided torticollis, plagiocephaly, expressive language disorder, and dysphagia. He will require 24-hour nursing care for the rest of his life.

PARENT'S CLAIM: The CNM failed to consult an ObGyn to determine whether the patient needed an urgent cesarean delivery when FHR monitoring first indicated a worrisome fetal heart rate. The CNM improperly increased the dosage of oxytocin and did not remain at the mother’s bedside until she was fully dilated and began pushing. The CNM failed to rule out placental abruption or to communicate to the ObGyn that there was bloody show in vaginal fluid. The CNM interpreted the maternal heart rate as a reassuring fetal heart rate. When the monitor was reattached, the CNM failed to call for emergency assistance, despite signs of acute fetal distress. Testing ruled out any preexisting neurologic injury or congenital defect.

DEFENDANT'S DEFENSE: The CNM claimed that she delegated the heart monitoring to the labor nurse and relied on the nurse to report any irregularities. The case was settled during the trial.

VERDICT: A $3 million Virginia settlement was reached, which included $2.1M for the infant and $.9M for the mother.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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