Patrice Wendling

Metastatic triple-negative breast cancer appears to be the latest hard-to-treat cancer to yield to the juggernaut that is now anti-PD-L1 immunotherapy.

MPDL3280L, an investigational monoclonal antibody against programmed death ligand 1 (PD-L1), posted an overall response rate of 19% among 21 evaluable patients in a phase Ia trial (95% confidence interval, 5-42).

© 2015 AACR/Todd Buchanan

This included two complete responses in patients with high PD-L1 expression and two partial responses. Three of the four responses are ongoing, Dr. Leisha Emens reported at the annual meeting of the American Association for Cancer Research.

“I think it very well could be the first targeted therapy that bears out in a larger trial,” she said during a press briefing. “These data are still early, and we need to enroll and treat a lot more patients with this agent, but I think it has great, great promise for this particular breast cancer subtype.”

There is great unmet need for new treatments in triple-negative breast cancer (TNBC) because it has a worse prognosis than other breast cancer subtypes do, and the only approved treatment option in the United States is chemotherapy.

TNBC is a good candidate for immunotherapy, particularly PD-L1 targeted therapies, because it has a higher mutation rate than do other breast cancer subtypes. This produces neoantigens that can be recognized as foreign by the immune system and be more effective targets for an immune response, Dr. Emens of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, explained.

TNBC also has higher PD-L1 expression levels, which can inhibit T-cell antitumor responses, and more tumor-infiltrating lymphocytes, which can facilitate a immune response and are associated with improved outcomes when present in high numbers.

MPDL3280A is designed to inhibit the binding of PD-L1 to programmed death receptor 1 (PD-1) and B7.1, which can restore antitumor T-cell activity and enhance T-cell priming, she said.

The checkpoint inhibitor received breakthrough therapy designation for metastatic bladder cancer in 2014 and a second designation in non–small cell lung cancer in February.

The ongoing phase Ia trial enrolled 54 women with metastatic TNBC and an ECOG performance status of 0 or 1. This included 21 patients initially selected for high PD-L1 expression levels (at least 5%) on their immune cells and 33 all-comers. MPDL3280A intravenous infusions were given every 3 weeks at doses of 15 mg/kg, 20 mg/kg, or 1,200 mg. Efficacy was evaluated in the 21 patients and safety in all 54 patients.

At 24 weeks, progression-free survival was 27% (95% CI, 7-47), Dr. Emens said.The median duration of response (range, 18-56+ weeks) has not been reached.

Three patients with progressive disease experienced pseudoprogression, where the target lesion shrank, but new lesions developed. Pseudoprogression, a feature of checkpoint inhibition that also has been seen with ipilimumab (Yervoy), is new for many physicians to manage and requires the patient’s entire clinical picture be taken into account, Dr. Emens said.

“An important component of the phenomenon of pseudoprogression is that if you see evidence of new lesions on a scan and the patient’s doing clinically well, you continue to treat and then reevaluate subsequent to that,” she said. “If there’s progression at that point, then potentially you consider changing the therapy or just following the patient more closely. Another potential option to help sort through that is to try and obtain tissue from one of those lesions to get some idea of what is happening, if it’s a phenomenon of the inflammatory response or a response to the therapy.”

Dr. Emens detailed one such case in which three target lesions decreased in size from baseline on 9- and 20-month follow-up scans, but newly enlarged axillary nodes that appeared inflammatory or necrotic developed near the third target lesion at 9 months. The patient remained on therapy and is doing well today, with further shrinkage of the target lesion and regression of the axillary nodes at 20 months.

MPDL3280A was generally well tolerated, with fatigue, nausea, fever, decreased appetite, and asthenia being the most common adverse events, Dr. Emens said. In all, 11% of patients experienced grade 3 treatment-related events. Two deaths, assessed as drug related by the investigator, are under investigation.

Press briefing moderator Louis M. Winer, director of the Georgetown Lombardi Comprehensive Cancer Center, commented that it wasn’t that long ago that phase I investigators were pleased if they saw even a hint of activity that would justify moving forward to phase II. The activity signals with the checkpoint inhibitors, however, are “unequivocal” and the implications for the future treatment of people with triple negative breast cancer are “very, very exciting,” according to Dr. Winer.

Earlier in the meeting, stellar results with the checkpoint inhibitor pembrolizumab from the KEYNOTE-006 trial upended the treatment paradigm for advanced melanoma. Pembrolizumab has been evaluated in TNBC and the safety profile and responses are similar to those with MPDL3280A, Dr. Emens said.

A global phase III trial evaluating MPDL3280A in combination with paclitaxel (Abraxane) as first-line therapy for metastatic TNBC is preparing to launch.

[email protected]

On Twitter @pwendl

Metastatic triple-negative breast cancer appears to be the latest hard-to-treat cancer to yield to the juggernaut that is now anti-PD-L1 immunotherapy.

MPDL3280L, an investigational monoclonal antibody against programmed death ligand 1 (PD-L1), posted an overall response rate of 19% among 21 evaluable patients in a phase Ia trial (95% confidence interval, 5-42).

© 2015 AACR/Todd Buchanan

This included two complete responses in patients with high PD-L1 expression and two partial responses. Three of the four responses are ongoing, Dr. Leisha Emens reported at the annual meeting of the American Association for Cancer Research.

“I think it very well could be the first targeted therapy that bears out in a larger trial,” she said during a press briefing. “These data are still early, and we need to enroll and treat a lot more patients with this agent, but I think it has great, great promise for this particular breast cancer subtype.”

There is great unmet need for new treatments in triple-negative breast cancer (TNBC) because it has a worse prognosis than other breast cancer subtypes do, and the only approved treatment option in the United States is chemotherapy.

TNBC is a good candidate for immunotherapy, particularly PD-L1 targeted therapies, because it has a higher mutation rate than do other breast cancer subtypes. This produces neoantigens that can be recognized as foreign by the immune system and be more effective targets for an immune response, Dr. Emens of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, explained.

TNBC also has higher PD-L1 expression levels, which can inhibit T-cell antitumor responses, and more tumor-infiltrating lymphocytes, which can facilitate a immune response and are associated with improved outcomes when present in high numbers.

MPDL3280A is designed to inhibit the binding of PD-L1 to programmed death receptor 1 (PD-1) and B7.1, which can restore antitumor T-cell activity and enhance T-cell priming, she said.

The checkpoint inhibitor received breakthrough therapy designation for metastatic bladder cancer in 2014 and a second designation in non–small cell lung cancer in February.

The ongoing phase Ia trial enrolled 54 women with metastatic TNBC and an ECOG performance status of 0 or 1. This included 21 patients initially selected for high PD-L1 expression levels (at least 5%) on their immune cells and 33 all-comers. MPDL3280A intravenous infusions were given every 3 weeks at doses of 15 mg/kg, 20 mg/kg, or 1,200 mg. Efficacy was evaluated in the 21 patients and safety in all 54 patients.

At 24 weeks, progression-free survival was 27% (95% CI, 7-47), Dr. Emens said.The median duration of response (range, 18-56+ weeks) has not been reached.

Three patients with progressive disease experienced pseudoprogression, where the target lesion shrank, but new lesions developed. Pseudoprogression, a feature of checkpoint inhibition that also has been seen with ipilimumab (Yervoy), is new for many physicians to manage and requires the patient’s entire clinical picture be taken into account, Dr. Emens said.

“An important component of the phenomenon of pseudoprogression is that if you see evidence of new lesions on a scan and the patient’s doing clinically well, you continue to treat and then reevaluate subsequent to that,” she said. “If there’s progression at that point, then potentially you consider changing the therapy or just following the patient more closely. Another potential option to help sort through that is to try and obtain tissue from one of those lesions to get some idea of what is happening, if it’s a phenomenon of the inflammatory response or a response to the therapy.”

Dr. Emens detailed one such case in which three target lesions decreased in size from baseline on 9- and 20-month follow-up scans, but newly enlarged axillary nodes that appeared inflammatory or necrotic developed near the third target lesion at 9 months. The patient remained on therapy and is doing well today, with further shrinkage of the target lesion and regression of the axillary nodes at 20 months.

MPDL3280A was generally well tolerated, with fatigue, nausea, fever, decreased appetite, and asthenia being the most common adverse events, Dr. Emens said. In all, 11% of patients experienced grade 3 treatment-related events. Two deaths, assessed as drug related by the investigator, are under investigation.

Press briefing moderator Louis M. Winer, director of the Georgetown Lombardi Comprehensive Cancer Center, commented that it wasn’t that long ago that phase I investigators were pleased if they saw even a hint of activity that would justify moving forward to phase II. The activity signals with the checkpoint inhibitors, however, are “unequivocal” and the implications for the future treatment of people with triple negative breast cancer are “very, very exciting,” according to Dr. Winer.

Earlier in the meeting, stellar results with the checkpoint inhibitor pembrolizumab from the KEYNOTE-006 trial upended the treatment paradigm for advanced melanoma. Pembrolizumab has been evaluated in TNBC and the safety profile and responses are similar to those with MPDL3280A, Dr. Emens said.

A global phase III trial evaluating MPDL3280A in combination with paclitaxel (Abraxane) as first-line therapy for metastatic TNBC is preparing to launch.

[email protected]

On Twitter @pwendl

Metastatic triple-negative breast cancer appears to be the latest hard-to-treat cancer to yield to the juggernaut that is now anti-PD-L1 immunotherapy.

MPDL3280L, an investigational monoclonal antibody against programmed death ligand 1 (PD-L1), posted an overall response rate of 19% among 21 evaluable patients in a phase Ia trial (95% confidence interval, 5-42).

© 2015 AACR/Todd Buchanan

This included two complete responses in patients with high PD-L1 expression and two partial responses. Three of the four responses are ongoing, Dr. Leisha Emens reported at the annual meeting of the American Association for Cancer Research.

“I think it very well could be the first targeted therapy that bears out in a larger trial,” she said during a press briefing. “These data are still early, and we need to enroll and treat a lot more patients with this agent, but I think it has great, great promise for this particular breast cancer subtype.”

There is great unmet need for new treatments in triple-negative breast cancer (TNBC) because it has a worse prognosis than other breast cancer subtypes do, and the only approved treatment option in the United States is chemotherapy.

TNBC is a good candidate for immunotherapy, particularly PD-L1 targeted therapies, because it has a higher mutation rate than do other breast cancer subtypes. This produces neoantigens that can be recognized as foreign by the immune system and be more effective targets for an immune response, Dr. Emens of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, explained.

TNBC also has higher PD-L1 expression levels, which can inhibit T-cell antitumor responses, and more tumor-infiltrating lymphocytes, which can facilitate a immune response and are associated with improved outcomes when present in high numbers.

MPDL3280A is designed to inhibit the binding of PD-L1 to programmed death receptor 1 (PD-1) and B7.1, which can restore antitumor T-cell activity and enhance T-cell priming, she said.

The checkpoint inhibitor received breakthrough therapy designation for metastatic bladder cancer in 2014 and a second designation in non–small cell lung cancer in February.

The ongoing phase Ia trial enrolled 54 women with metastatic TNBC and an ECOG performance status of 0 or 1. This included 21 patients initially selected for high PD-L1 expression levels (at least 5%) on their immune cells and 33 all-comers. MPDL3280A intravenous infusions were given every 3 weeks at doses of 15 mg/kg, 20 mg/kg, or 1,200 mg. Efficacy was evaluated in the 21 patients and safety in all 54 patients.

At 24 weeks, progression-free survival was 27% (95% CI, 7-47), Dr. Emens said.The median duration of response (range, 18-56+ weeks) has not been reached.

Three patients with progressive disease experienced pseudoprogression, where the target lesion shrank, but new lesions developed. Pseudoprogression, a feature of checkpoint inhibition that also has been seen with ipilimumab (Yervoy), is new for many physicians to manage and requires the patient’s entire clinical picture be taken into account, Dr. Emens said.

“An important component of the phenomenon of pseudoprogression is that if you see evidence of new lesions on a scan and the patient’s doing clinically well, you continue to treat and then reevaluate subsequent to that,” she said. “If there’s progression at that point, then potentially you consider changing the therapy or just following the patient more closely. Another potential option to help sort through that is to try and obtain tissue from one of those lesions to get some idea of what is happening, if it’s a phenomenon of the inflammatory response or a response to the therapy.”

Dr. Emens detailed one such case in which three target lesions decreased in size from baseline on 9- and 20-month follow-up scans, but newly enlarged axillary nodes that appeared inflammatory or necrotic developed near the third target lesion at 9 months. The patient remained on therapy and is doing well today, with further shrinkage of the target lesion and regression of the axillary nodes at 20 months.

MPDL3280A was generally well tolerated, with fatigue, nausea, fever, decreased appetite, and asthenia being the most common adverse events, Dr. Emens said. In all, 11% of patients experienced grade 3 treatment-related events. Two deaths, assessed as drug related by the investigator, are under investigation.

Press briefing moderator Louis M. Winer, director of the Georgetown Lombardi Comprehensive Cancer Center, commented that it wasn’t that long ago that phase I investigators were pleased if they saw even a hint of activity that would justify moving forward to phase II. The activity signals with the checkpoint inhibitors, however, are “unequivocal” and the implications for the future treatment of people with triple negative breast cancer are “very, very exciting,” according to Dr. Winer.

Earlier in the meeting, stellar results with the checkpoint inhibitor pembrolizumab from the KEYNOTE-006 trial upended the treatment paradigm for advanced melanoma. Pembrolizumab has been evaluated in TNBC and the safety profile and responses are similar to those with MPDL3280A, Dr. Emens said.

A global phase III trial evaluating MPDL3280A in combination with paclitaxel (Abraxane) as first-line therapy for metastatic TNBC is preparing to launch.

[email protected]

On Twitter @pwendl

Pembrolizumab was superior to ipilimumab, the standard of care, as first-line therapy for advanced melanoma in the phase III KEYNOTE-006 trial.

Pembrolizumab (Keytruda) hit all of its primary survival end points and nearly tripled response rates from 12% with ipilimumab (Yervoy) to 33% in the first frontline head-to-head comparison of the two immune checkpoint inhibitors.

Pembrolizumab reduced the risk of progression by 42% and the risk of death by 31% to 37%, compared with ipilimumab, study author Dr. Antoni Ribas reported at the annual meeting of the American Association for Cancer Research.

© 2015 AACR/Todd Buchanan

“We think that this data should change the paradigm of treatment for these patients, and the standard of care should quickly shift to giving PD-1 antibodies,” he said at a press briefing.

Pembrolizumab, a monoclonal antibody that inhibits programmed death receptor-1 (PD-1), is approved as second-line therapy for unresectable or metastatic melanoma after failing iplimumab or a BRAF inhibitor, if a BRAF V600 mutation is present.

Ipilimumab has been the gold standard against which everything else was measured, but “this is now expected to change the treatment landscape for melanoma. This is a very high impact trial,” Dr. Suzanne Topalian, director of the melanoma program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, said during the briefing.

The 2011 approval of ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, as first-line therapy for advanced melanoma was a landmark moment, she said, not only for melanoma because it was the first drug ever to show a survival advantage in a randomized trial, but also for immunotherapy because it was the first checkpoint blocker to show such a benefit.

Results of the KEYSTONE-006 trial, simultaneously published on line (N. Engl. J. Med. 2015. DOI: 10.1056/NEJMoa1503093), prompted the safety monitoring committee to recommend stopping the trial early and allowing ipilimumab patients to receive pembrolizumab.

© 2015 AACR/Todd Buchanan

Lead investigator Dr. Caroline Robert, head of dermatology at Institut Gustave-Roussy in Paris, said in a statement that she hoped the results would accelerate regulatory approval of pembrolizumab in Europe, where the drug is still not on the market.

KEYNOTE-006 included 834 patients with unresectable, ipilimumab-naive, stage III or IV melanoma treated with no more than one previous systemic therapy who were randomly assigned to 10 mg/kg pembrolizumab either every 2 weeks or every 3 weeks or four cycles of 3 mg/kg ipilimumab every 3 weeks, until disease progression or unacceptable toxicity. Treatment response was assessed 12 weeks after randomization and every 6 weeks thereafter per RECIST guideline v1.1 by central review and per immune-related response criteria by investigator review.

Two-thirds of patients were treatment naive, 79% had PD-ligand 1(PD-L1)-positive tumors, and 36% had BRAF V600-mutant tumors.

At the first interim analysis after a median follow-up of 8 months, 6-month progression-free survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (Hazard ratio, 0.58; P < .001), Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, reported.

The benefit was seen across all prespecified subgroups, including PD-L1-positive and PD-L1-negative tumors.

At the time of the analysis, responses by RECIST were ongoing in 89.4% of patients treated with pembrolizumab every 2 weeks, 96.7% on pembrolizumab every 3 weeks, and 88% given ipilumumab.

The median duration of response was 251 days in the pembrolizumab every 2 weeks-arm, but had not been reached in the other two arms.

There has been no evidence of resistance, and only a small minority, perhaps 5-10% of patients, have escape lesions or progress after response, he said.

At the second interim analysis after a median follow-up of 13.8 months, 1-year overall survival rates were 74% for pembrolizumab every 2 weeks (HR, 0.63; P = .0005), 68.4% for pembrolizumab every 3 weeks (HR, 0.69; P = .0036), and 58.2% for ipilimumab. The survival benefit extended to all subgroups, except the 18% of patients with PD-L1-negative tumors, although sample sizes were small and confidence intervals wide.

Efficacy and tolerability was similar for both pembrolizumab dosing schedules, Dr. Ribas said. Treatment-related grade 3-4 adverse events were lower in the pembrolizumab every 2 and 3 weeks arms than with ipilimumab (13.3% vs. 10.1% vs. 20%), despite exposure to pembrolizumab being nearly 3 times as long (164 days vs. 151.5 days vs. 50 days).

When asked how the findings would change his practice tomorrow, Dr. Ribas said pembrolizumab should be used first line but that he will continue to use ipilimumab, either alone or in combination with a PD-1 inhibitor, because it can give durable responses. The critical unanswered question of what the most effective sequence or combination of checkpoint inhibitors is will take years to answer.

“This is just the start,” he said. “This is amazing that single-agent checkpoint blockade gives these responses in melanoma and as you will see in lung cancer, but the reality is that there’s two-thirds of patients who do not respond and we have to do something about that.”

The study was funded by Merck Sharp & Dohme. Dr. Ribas is a consultant to Merck, with the honoraria paid to his institution. Dr. Robert is a consultant with honoraria for MSD, Bristol Myers Squibb, Roche, Novartis, GlaxoSmithKline, and Amgen.

[email protected]

Pembrolizumab was superior to ipilimumab, the standard of care, as first-line therapy for advanced melanoma in the phase III KEYNOTE-006 trial.

Pembrolizumab (Keytruda) hit all of its primary survival end points and nearly tripled response rates from 12% with ipilimumab (Yervoy) to 33% in the first frontline head-to-head comparison of the two immune checkpoint inhibitors.

Pembrolizumab reduced the risk of progression by 42% and the risk of death by 31% to 37%, compared with ipilimumab, study author Dr. Antoni Ribas reported at the annual meeting of the American Association for Cancer Research.

© 2015 AACR/Todd Buchanan

“We think that this data should change the paradigm of treatment for these patients, and the standard of care should quickly shift to giving PD-1 antibodies,” he said at a press briefing.

Pembrolizumab, a monoclonal antibody that inhibits programmed death receptor-1 (PD-1), is approved as second-line therapy for unresectable or metastatic melanoma after failing iplimumab or a BRAF inhibitor, if a BRAF V600 mutation is present.

Ipilimumab has been the gold standard against which everything else was measured, but “this is now expected to change the treatment landscape for melanoma. This is a very high impact trial,” Dr. Suzanne Topalian, director of the melanoma program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, said during the briefing.

The 2011 approval of ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, as first-line therapy for advanced melanoma was a landmark moment, she said, not only for melanoma because it was the first drug ever to show a survival advantage in a randomized trial, but also for immunotherapy because it was the first checkpoint blocker to show such a benefit.

Results of the KEYSTONE-006 trial, simultaneously published on line (N. Engl. J. Med. 2015. DOI: 10.1056/NEJMoa1503093), prompted the safety monitoring committee to recommend stopping the trial early and allowing ipilimumab patients to receive pembrolizumab.

© 2015 AACR/Todd Buchanan

Lead investigator Dr. Caroline Robert, head of dermatology at Institut Gustave-Roussy in Paris, said in a statement that she hoped the results would accelerate regulatory approval of pembrolizumab in Europe, where the drug is still not on the market.

KEYNOTE-006 included 834 patients with unresectable, ipilimumab-naive, stage III or IV melanoma treated with no more than one previous systemic therapy who were randomly assigned to 10 mg/kg pembrolizumab either every 2 weeks or every 3 weeks or four cycles of 3 mg/kg ipilimumab every 3 weeks, until disease progression or unacceptable toxicity. Treatment response was assessed 12 weeks after randomization and every 6 weeks thereafter per RECIST guideline v1.1 by central review and per immune-related response criteria by investigator review.

Two-thirds of patients were treatment naive, 79% had PD-ligand 1(PD-L1)-positive tumors, and 36% had BRAF V600-mutant tumors.

At the first interim analysis after a median follow-up of 8 months, 6-month progression-free survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (Hazard ratio, 0.58; P < .001), Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, reported.

The benefit was seen across all prespecified subgroups, including PD-L1-positive and PD-L1-negative tumors.

At the time of the analysis, responses by RECIST were ongoing in 89.4% of patients treated with pembrolizumab every 2 weeks, 96.7% on pembrolizumab every 3 weeks, and 88% given ipilumumab.

The median duration of response was 251 days in the pembrolizumab every 2 weeks-arm, but had not been reached in the other two arms.

There has been no evidence of resistance, and only a small minority, perhaps 5-10% of patients, have escape lesions or progress after response, he said.

At the second interim analysis after a median follow-up of 13.8 months, 1-year overall survival rates were 74% for pembrolizumab every 2 weeks (HR, 0.63; P = .0005), 68.4% for pembrolizumab every 3 weeks (HR, 0.69; P = .0036), and 58.2% for ipilimumab. The survival benefit extended to all subgroups, except the 18% of patients with PD-L1-negative tumors, although sample sizes were small and confidence intervals wide.

Efficacy and tolerability was similar for both pembrolizumab dosing schedules, Dr. Ribas said. Treatment-related grade 3-4 adverse events were lower in the pembrolizumab every 2 and 3 weeks arms than with ipilimumab (13.3% vs. 10.1% vs. 20%), despite exposure to pembrolizumab being nearly 3 times as long (164 days vs. 151.5 days vs. 50 days).

When asked how the findings would change his practice tomorrow, Dr. Ribas said pembrolizumab should be used first line but that he will continue to use ipilimumab, either alone or in combination with a PD-1 inhibitor, because it can give durable responses. The critical unanswered question of what the most effective sequence or combination of checkpoint inhibitors is will take years to answer.

“This is just the start,” he said. “This is amazing that single-agent checkpoint blockade gives these responses in melanoma and as you will see in lung cancer, but the reality is that there’s two-thirds of patients who do not respond and we have to do something about that.”

The study was funded by Merck Sharp & Dohme. Dr. Ribas is a consultant to Merck, with the honoraria paid to his institution. Dr. Robert is a consultant with honoraria for MSD, Bristol Myers Squibb, Roche, Novartis, GlaxoSmithKline, and Amgen.

[email protected]

Pembrolizumab was superior to ipilimumab, the standard of care, as first-line therapy for advanced melanoma in the phase III KEYNOTE-006 trial.

Pembrolizumab (Keytruda) hit all of its primary survival end points and nearly tripled response rates from 12% with ipilimumab (Yervoy) to 33% in the first frontline head-to-head comparison of the two immune checkpoint inhibitors.

Pembrolizumab reduced the risk of progression by 42% and the risk of death by 31% to 37%, compared with ipilimumab, study author Dr. Antoni Ribas reported at the annual meeting of the American Association for Cancer Research.

© 2015 AACR/Todd Buchanan

“We think that this data should change the paradigm of treatment for these patients, and the standard of care should quickly shift to giving PD-1 antibodies,” he said at a press briefing.

Pembrolizumab, a monoclonal antibody that inhibits programmed death receptor-1 (PD-1), is approved as second-line therapy for unresectable or metastatic melanoma after failing iplimumab or a BRAF inhibitor, if a BRAF V600 mutation is present.

Ipilimumab has been the gold standard against which everything else was measured, but “this is now expected to change the treatment landscape for melanoma. This is a very high impact trial,” Dr. Suzanne Topalian, director of the melanoma program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, said during the briefing.

The 2011 approval of ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, as first-line therapy for advanced melanoma was a landmark moment, she said, not only for melanoma because it was the first drug ever to show a survival advantage in a randomized trial, but also for immunotherapy because it was the first checkpoint blocker to show such a benefit.

Results of the KEYSTONE-006 trial, simultaneously published on line (N. Engl. J. Med. 2015. DOI: 10.1056/NEJMoa1503093), prompted the safety monitoring committee to recommend stopping the trial early and allowing ipilimumab patients to receive pembrolizumab.

© 2015 AACR/Todd Buchanan

Lead investigator Dr. Caroline Robert, head of dermatology at Institut Gustave-Roussy in Paris, said in a statement that she hoped the results would accelerate regulatory approval of pembrolizumab in Europe, where the drug is still not on the market.

KEYNOTE-006 included 834 patients with unresectable, ipilimumab-naive, stage III or IV melanoma treated with no more than one previous systemic therapy who were randomly assigned to 10 mg/kg pembrolizumab either every 2 weeks or every 3 weeks or four cycles of 3 mg/kg ipilimumab every 3 weeks, until disease progression or unacceptable toxicity. Treatment response was assessed 12 weeks after randomization and every 6 weeks thereafter per RECIST guideline v1.1 by central review and per immune-related response criteria by investigator review.

Two-thirds of patients were treatment naive, 79% had PD-ligand 1(PD-L1)-positive tumors, and 36% had BRAF V600-mutant tumors.

At the first interim analysis after a median follow-up of 8 months, 6-month progression-free survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (Hazard ratio, 0.58; P < .001), Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, reported.

The benefit was seen across all prespecified subgroups, including PD-L1-positive and PD-L1-negative tumors.

At the time of the analysis, responses by RECIST were ongoing in 89.4% of patients treated with pembrolizumab every 2 weeks, 96.7% on pembrolizumab every 3 weeks, and 88% given ipilumumab.

The median duration of response was 251 days in the pembrolizumab every 2 weeks-arm, but had not been reached in the other two arms.

There has been no evidence of resistance, and only a small minority, perhaps 5-10% of patients, have escape lesions or progress after response, he said.

At the second interim analysis after a median follow-up of 13.8 months, 1-year overall survival rates were 74% for pembrolizumab every 2 weeks (HR, 0.63; P = .0005), 68.4% for pembrolizumab every 3 weeks (HR, 0.69; P = .0036), and 58.2% for ipilimumab. The survival benefit extended to all subgroups, except the 18% of patients with PD-L1-negative tumors, although sample sizes were small and confidence intervals wide.

Efficacy and tolerability was similar for both pembrolizumab dosing schedules, Dr. Ribas said. Treatment-related grade 3-4 adverse events were lower in the pembrolizumab every 2 and 3 weeks arms than with ipilimumab (13.3% vs. 10.1% vs. 20%), despite exposure to pembrolizumab being nearly 3 times as long (164 days vs. 151.5 days vs. 50 days).

When asked how the findings would change his practice tomorrow, Dr. Ribas said pembrolizumab should be used first line but that he will continue to use ipilimumab, either alone or in combination with a PD-1 inhibitor, because it can give durable responses. The critical unanswered question of what the most effective sequence or combination of checkpoint inhibitors is will take years to answer.

“This is just the start,” he said. “This is amazing that single-agent checkpoint blockade gives these responses in melanoma and as you will see in lung cancer, but the reality is that there’s two-thirds of patients who do not respond and we have to do something about that.”

The study was funded by Merck Sharp & Dohme. Dr. Ribas is a consultant to Merck, with the honoraria paid to his institution. Dr. Robert is a consultant with honoraria for MSD, Bristol Myers Squibb, Roche, Novartis, GlaxoSmithKline, and Amgen.

[email protected]

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

[email protected]

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

[email protected]

CHICAGO – Health care data theft represents a far greater threat than theft of credit card, financial, and banking information.

The reasons are simple: stolen health care records have a longer shelf life and offer a higher payout on the black market, James Trainor, deputy assistant director of the Federal Bureau of Investigation’s Cyber Division, said at the annual meeting of the Healthcare Information Management Systems Society.

Patrice Wendling/Frontline Medical News

When credit cards are stolen it’s pretty easy to identify the information on cyber crime forums and compensate for loss, so the value of that stolen credit card or bank record has a certain shelf life. For health care records, it’s harder to identify where those stolen records may end up and as such it creates a greater challenge for law enforcement.

The opportunity to exploit and monetize stolen health care data for various forms of fraud such as identity, Medicaid, tax, medical device, and pharmaceutical fraud increases the value at which they can be sold online.

“Actually, it’s one of the primary reasons why criminal organizations go after health care records,” Mr. Trainor said.

Not surprisingly, the FBI rates health care data theft as a Tier 1 priority, capable of causing “catastrophic or severe harm.”

And the problem is growing. Two years ago, a significant cyber intrusion occurred every 2 weeks; now it happens every 2-3 days.

“The pace is growing rapidly, the volume of data that’s being [stolen] is substantially increasing, and it just requires a much more robust response across the U.S. government and private sector,” said Mr. Trainor, who helped investigate the December 2014 Sony cyber attack.

Some of the unique challenges to the health care sector are the use of legacy computer systems, “bring your own device” policies, and increased volume of data following the transition to electronic health records, and stolen protected health information isn’t readily discovered, he said. The range, size, and capability of IT infrastructure varies dramatically as do the funding and resources needed to keep up with the rapidly changing IT field.

Other challenges include video conferencing systems, digital video systems used for consultations and remote procedures, and Internet-connected medical devices such as insulin pumps, pacemakers, and MRI machines, said Kevin Hemsley, a project manager at the Idaho National Laboratory supporting the Department of Homeland Security’s Industrial Control Systems Computer Emergency Response Team.

Patrice Wendling/Frontline Medical News

While providers love the ability to use the Internet to control and monitor devices, ingrained security mechanisms can be minimal. This makes for low-hanging fruit for thieves who can enter the system and even lock up an otherwise safe device.

Mr. Hemsley noted that a 2014 report by the Internet security and training firm SANS found that 33% of malicious traffic passed through or was transmitted from VPN applications and devices versus 16% from firewalls, 7% from routers, and 3% from enterprise network controllers.

“One of the messages here is to look at cyber security as being more than HIPPA, it’s patient safety,” he said.

Both experts advised physicians and other health care providers to update their privacy and security software frequently. Available resources include the FBI’s 24-hour CyWatch (855-292-3937/[email protected]), Cyber Task Force (with 56 local field offices), and for individuals, the Internet Crime Complaint Center (www.ic3.gov).

Speedy communication with officials following a data breech is important not just to get the institution’s system back up and running, but it allows officials to identify data footprints left by hackers before they are destroyed, Mr. Trainor said.

In two of the three recent high profile health care cyber attacks involving Community Health Systems (4.5 million accounts), Anthem Blue Cross Blue Shield (78 million records), and Premera Blue Cross (11 million consumers), the institutions contacted the FBI, but in one unnamed case, the FBI had to make the call, he pointed out.

[email protected]

CHICAGO – A national survey of 1,246 residents found no evidence that taking a commercial board-review course provides any benefit in passing the American Board of Surgery certifying exam.

And none of the courses was significantly better than another, reported Dr. Mark Malangoni, an ACS Fellow and ABS associate executive director.

“Exam-review courses are now a multibillion-dollar industry … but there is little evidence to suggest they actually improve exam performance,” he said.

Dr. Malangoni and his ABS colleagues electronically surveyed 1,396 candidates who took the ABS certifying exam (CE) during the 2012-2013 academic year. Of the 1,246 who responded, 974 (78%) had taken a review course. Another 140 candidates declined to respond to the two-question survey, but their CE test results were available for comparison.

Among first-time examinees, the CE pass rate was 83.7% with any review course, 80.7% with no course, and 75.6% for the nonresponders, Dr. Malangoni said at the annual meeting of the Central Surgical Association.

Among those who had taken the CE before, pass rates were 77%, 69%, and 58%, respectively, with the intergroup difference statistically significant only for the nonresponders (P value = .01).

Despite the lack of benefit, however, most examinees (64%) believed that the review course improved their preparation for the CE, he said.

Those repeating the CE were significantly more likely than first-time examinees to take a review course (84.6% vs. 76.1%; P = .002).

Several candidates decided that multiple review courses might be better: 16% of the first-time examinees and 32% of the repeat examinees. Again, pass rates were not significantly different with multiple courses, Dr. Malangoni said.

The survey identified nine commercially available courses, but five were not analyzed because there were no enrollees or a low number (≤ 40) of enrollees. The remaining four courses were assigned a letter for anonymity. Enrollment in all courses ranged from 21 to 706 students.

In multivariate analysis, the only significant predictor for passing the initial CE was the qualifying examination scale score (Odds ratio, 1.09; P < .001). Course D trended toward a benefit, but the 99% confidence intervals overlapped and the P value did not meet the predetermined threshold of ≤ .01 (OR, 3.25; P = .02; 99% CI 0.86-12.22), he said.

For repeat examinees, no variables including the four review courses, gender, program size, or international medical graduation significantly predicted success on the CE exam.

“Given the time and effort, and expense, we feel that CE candidates should consider these results when assessing how best to prepare for this examination,” Dr. Malangoni concluded.

The study is not the first to question the benefit of review courses for already cash-strapped medical students and residents (N. Engl. J. Med. 2011:365:104-5), he noted.

Dr. Malangoni balked, however, at suggesting review courses may not be worth the investment for any candidate.

“Our results are applicable to a large group; however, it is not possible to determine when taking a review course would be beneficial for a specific candidate,” he said in an interview.

Dr. Malangoni reported having no financial disclosures.

[email protected]

On Twitter @pwendl

CHICAGO – A national survey of 1,246 residents found no evidence that taking a commercial board-review course provides any benefit in passing the American Board of Surgery certifying exam.

And none of the courses was significantly better than another, reported Dr. Mark Malangoni, an ACS Fellow and ABS associate executive director.

“Exam-review courses are now a multibillion-dollar industry … but there is little evidence to suggest they actually improve exam performance,” he said.

Dr. Malangoni and his ABS colleagues electronically surveyed 1,396 candidates who took the ABS certifying exam (CE) during the 2012-2013 academic year. Of the 1,246 who responded, 974 (78%) had taken a review course. Another 140 candidates declined to respond to the two-question survey, but their CE test results were available for comparison.

Among first-time examinees, the CE pass rate was 83.7% with any review course, 80.7% with no course, and 75.6% for the nonresponders, Dr. Malangoni said at the annual meeting of the Central Surgical Association.

Among those who had taken the CE before, pass rates were 77%, 69%, and 58%, respectively, with the intergroup difference statistically significant only for the nonresponders (P value = .01).

Despite the lack of benefit, however, most examinees (64%) believed that the review course improved their preparation for the CE, he said.

Those repeating the CE were significantly more likely than first-time examinees to take a review course (84.6% vs. 76.1%; P = .002).

Several candidates decided that multiple review courses might be better: 16% of the first-time examinees and 32% of the repeat examinees. Again, pass rates were not significantly different with multiple courses, Dr. Malangoni said.

The survey identified nine commercially available courses, but five were not analyzed because there were no enrollees or a low number (≤ 40) of enrollees. The remaining four courses were assigned a letter for anonymity. Enrollment in all courses ranged from 21 to 706 students.

In multivariate analysis, the only significant predictor for passing the initial CE was the qualifying examination scale score (Odds ratio, 1.09; P < .001). Course D trended toward a benefit, but the 99% confidence intervals overlapped and the P value did not meet the predetermined threshold of ≤ .01 (OR, 3.25; P = .02; 99% CI 0.86-12.22), he said.

For repeat examinees, no variables including the four review courses, gender, program size, or international medical graduation significantly predicted success on the CE exam.

“Given the time and effort, and expense, we feel that CE candidates should consider these results when assessing how best to prepare for this examination,” Dr. Malangoni concluded.

The study is not the first to question the benefit of review courses for already cash-strapped medical students and residents (N. Engl. J. Med. 2011:365:104-5), he noted.

Dr. Malangoni balked, however, at suggesting review courses may not be worth the investment for any candidate.

“Our results are applicable to a large group; however, it is not possible to determine when taking a review course would be beneficial for a specific candidate,” he said in an interview.

Dr. Malangoni reported having no financial disclosures.

[email protected]

On Twitter @pwendl

CHICAGO – A national survey of 1,246 residents found no evidence that taking a commercial board-review course provides any benefit in passing the American Board of Surgery certifying exam.

And none of the courses was significantly better than another, reported Dr. Mark Malangoni, an ACS Fellow and ABS associate executive director.

“Exam-review courses are now a multibillion-dollar industry … but there is little evidence to suggest they actually improve exam performance,” he said.

Dr. Malangoni and his ABS colleagues electronically surveyed 1,396 candidates who took the ABS certifying exam (CE) during the 2012-2013 academic year. Of the 1,246 who responded, 974 (78%) had taken a review course. Another 140 candidates declined to respond to the two-question survey, but their CE test results were available for comparison.

Among first-time examinees, the CE pass rate was 83.7% with any review course, 80.7% with no course, and 75.6% for the nonresponders, Dr. Malangoni said at the annual meeting of the Central Surgical Association.

Among those who had taken the CE before, pass rates were 77%, 69%, and 58%, respectively, with the intergroup difference statistically significant only for the nonresponders (P value = .01).

Despite the lack of benefit, however, most examinees (64%) believed that the review course improved their preparation for the CE, he said.

Those repeating the CE were significantly more likely than first-time examinees to take a review course (84.6% vs. 76.1%; P = .002).

Several candidates decided that multiple review courses might be better: 16% of the first-time examinees and 32% of the repeat examinees. Again, pass rates were not significantly different with multiple courses, Dr. Malangoni said.

The survey identified nine commercially available courses, but five were not analyzed because there were no enrollees or a low number (≤ 40) of enrollees. The remaining four courses were assigned a letter for anonymity. Enrollment in all courses ranged from 21 to 706 students.

In multivariate analysis, the only significant predictor for passing the initial CE was the qualifying examination scale score (Odds ratio, 1.09; P < .001). Course D trended toward a benefit, but the 99% confidence intervals overlapped and the P value did not meet the predetermined threshold of ≤ .01 (OR, 3.25; P = .02; 99% CI 0.86-12.22), he said.

For repeat examinees, no variables including the four review courses, gender, program size, or international medical graduation significantly predicted success on the CE exam.

“Given the time and effort, and expense, we feel that CE candidates should consider these results when assessing how best to prepare for this examination,” Dr. Malangoni concluded.

The study is not the first to question the benefit of review courses for already cash-strapped medical students and residents (N. Engl. J. Med. 2011:365:104-5), he noted.

Dr. Malangoni balked, however, at suggesting review courses may not be worth the investment for any candidate.

“Our results are applicable to a large group; however, it is not possible to determine when taking a review course would be beneficial for a specific candidate,” he said in an interview.

Dr. Malangoni reported having no financial disclosures.

[email protected]

On Twitter @pwendl

CHICAGO – The federal government’s Shared Nationwide Interoperability Roadmap lays out a grand vision for a single health IT ecosystem, but will it be able to enforce its own standards or be able to meaningfully incorporate the flood of patient-provided data in an era of Fitbits and Apple watches?

Those were just a few of the concerns heard by the officials from the Office of the National Coordinator for Health Information Technology (ONC) at the annual meeting of the Healthcare Information and Management Systems Society.

Patrice Wendling/Frontline Medical News

During a listening session on the Roadmap, one attendee called for oversight and a transparent process to handle complaints much like the airline industry has for lost luggage, observing that providers already have a hard time getting industry to recognize and “play ball” with each other.

Rules of engagement and governance are one of the core building blocks of the Roadmap, with the ONC establishing a governance framework with rules of the road and identifying a mechanism to recognize organizations that comply with that framework. That could be thought of as a mechanism for advancing some accountability, but it’s important to remember that participation in that process will be voluntary, according to Erica Galvez, interoperability portfolio manager at ONC.

“So unless that’s tied to other policy levers ... or other enforcement authorities, ONC, given its current authority, has quite a few limitations on its ability to actually affect the type of enforcement you’re alluding to,” she added.

The ONC does have proposals for in-field surveillance of products and additional transparency requirements associated with products, said Steven Posnack, director of the ONC Office of Standards and Technology. Still, the ONC doesn’t necessarily have all the “arrows and quivers” needed to affect the enforcement and accountability some would like, he acknowledged.

Patrice Wendling/Frontline Medical News

Core technical standards and functions designed to help achieve the Roadmap’s 3-, 6-, and 10-year milestones include consistent data formats and semantics; consistent, secure transport techniques; standard, secure services; accurate patient identity matching; and reliable resource location.

One physician attendee called for standardizing the standards themselves, noting that there are more than 150 terminologies in use, each with its own idiosyncrasies. One approach may be to follow the example set by global IT organizations like Facebook, LinkedIn, and Yahoo, which converged on using the Web standards as a means to have persistent, authoritative URIs (uniform resource identifiers) that can be shared globally, he suggested to a round of applause.

Another attendee called for future drafts of the Roadmap to address an increasing trend among biopharmaceutical companies to create their own portals or mobile apps for a specific therapy, which requires providers to download multiple infrastructures to support various therapies.

Still another attendee artfully asked that Departments of Defense and Veterans Affairs medical records be incorporated into the proposed nationwide IT system to ensure meaningful longitudinal care for veterans.

There was little audience discussion about the Roadmap’s other core building blocks of a common clinical data set or privacy and security. Concerns about medical device interoperability, however, were raised from the floor and have been echoed in the public comments received by the ONC, Ms. Galvez said.

She stressed that the Roadmap is a shared plan that attempts to capture both public and private sector activities.

“We’re not going to achieve interoperability at the scale we are attempting with government action alone,” Ms. Galvez said. “In looking at some of the early public comments, I will say I have not seen as many commitments from folks as I would really like to see. I’d really like to see organizations coming forward and saying ‘There’s a call to action in this space, we think there’s something we can do about that, and here’s what we’re willing to do.’ ”

The public comment period on the Roadmap officially closed April 3, but comments on the ONC’s 2015 Interoperability Standards Advisory will be accepted through May 1.

[email protected]

CHICAGO – The federal government’s Shared Nationwide Interoperability Roadmap lays out a grand vision for a single health IT ecosystem, but will it be able to enforce its own standards or be able to meaningfully incorporate the flood of patient-provided data in an era of Fitbits and Apple watches?

Those were just a few of the concerns heard by the officials from the Office of the National Coordinator for Health Information Technology (ONC) at the annual meeting of the Healthcare Information and Management Systems Society.

Patrice Wendling/Frontline Medical News

During a listening session on the Roadmap, one attendee called for oversight and a transparent process to handle complaints much like the airline industry has for lost luggage, observing that providers already have a hard time getting industry to recognize and “play ball” with each other.

Rules of engagement and governance are one of the core building blocks of the Roadmap, with the ONC establishing a governance framework with rules of the road and identifying a mechanism to recognize organizations that comply with that framework. That could be thought of as a mechanism for advancing some accountability, but it’s important to remember that participation in that process will be voluntary, according to Erica Galvez, interoperability portfolio manager at ONC.

“So unless that’s tied to other policy levers ... or other enforcement authorities, ONC, given its current authority, has quite a few limitations on its ability to actually affect the type of enforcement you’re alluding to,” she added.

The ONC does have proposals for in-field surveillance of products and additional transparency requirements associated with products, said Steven Posnack, director of the ONC Office of Standards and Technology. Still, the ONC doesn’t necessarily have all the “arrows and quivers” needed to affect the enforcement and accountability some would like, he acknowledged.

Patrice Wendling/Frontline Medical News

Core technical standards and functions designed to help achieve the Roadmap’s 3-, 6-, and 10-year milestones include consistent data formats and semantics; consistent, secure transport techniques; standard, secure services; accurate patient identity matching; and reliable resource location.

One physician attendee called for standardizing the standards themselves, noting that there are more than 150 terminologies in use, each with its own idiosyncrasies. One approach may be to follow the example set by global IT organizations like Facebook, LinkedIn, and Yahoo, which converged on using the Web standards as a means to have persistent, authoritative URIs (uniform resource identifiers) that can be shared globally, he suggested to a round of applause.

Another attendee called for future drafts of the Roadmap to address an increasing trend among biopharmaceutical companies to create their own portals or mobile apps for a specific therapy, which requires providers to download multiple infrastructures to support various therapies.

Still another attendee artfully asked that Departments of Defense and Veterans Affairs medical records be incorporated into the proposed nationwide IT system to ensure meaningful longitudinal care for veterans.

There was little audience discussion about the Roadmap’s other core building blocks of a common clinical data set or privacy and security. Concerns about medical device interoperability, however, were raised from the floor and have been echoed in the public comments received by the ONC, Ms. Galvez said.

She stressed that the Roadmap is a shared plan that attempts to capture both public and private sector activities.

“We’re not going to achieve interoperability at the scale we are attempting with government action alone,” Ms. Galvez said. “In looking at some of the early public comments, I will say I have not seen as many commitments from folks as I would really like to see. I’d really like to see organizations coming forward and saying ‘There’s a call to action in this space, we think there’s something we can do about that, and here’s what we’re willing to do.’ ”

The public comment period on the Roadmap officially closed April 3, but comments on the ONC’s 2015 Interoperability Standards Advisory will be accepted through May 1.

[email protected]

CHICAGO – The federal government’s Shared Nationwide Interoperability Roadmap lays out a grand vision for a single health IT ecosystem, but will it be able to enforce its own standards or be able to meaningfully incorporate the flood of patient-provided data in an era of Fitbits and Apple watches?

Those were just a few of the concerns heard by the officials from the Office of the National Coordinator for Health Information Technology (ONC) at the annual meeting of the Healthcare Information and Management Systems Society.

Patrice Wendling/Frontline Medical News

During a listening session on the Roadmap, one attendee called for oversight and a transparent process to handle complaints much like the airline industry has for lost luggage, observing that providers already have a hard time getting industry to recognize and “play ball” with each other.

Rules of engagement and governance are one of the core building blocks of the Roadmap, with the ONC establishing a governance framework with rules of the road and identifying a mechanism to recognize organizations that comply with that framework. That could be thought of as a mechanism for advancing some accountability, but it’s important to remember that participation in that process will be voluntary, according to Erica Galvez, interoperability portfolio manager at ONC.

“So unless that’s tied to other policy levers ... or other enforcement authorities, ONC, given its current authority, has quite a few limitations on its ability to actually affect the type of enforcement you’re alluding to,” she added.

The ONC does have proposals for in-field surveillance of products and additional transparency requirements associated with products, said Steven Posnack, director of the ONC Office of Standards and Technology. Still, the ONC doesn’t necessarily have all the “arrows and quivers” needed to affect the enforcement and accountability some would like, he acknowledged.

Patrice Wendling/Frontline Medical News

Core technical standards and functions designed to help achieve the Roadmap’s 3-, 6-, and 10-year milestones include consistent data formats and semantics; consistent, secure transport techniques; standard, secure services; accurate patient identity matching; and reliable resource location.

One physician attendee called for standardizing the standards themselves, noting that there are more than 150 terminologies in use, each with its own idiosyncrasies. One approach may be to follow the example set by global IT organizations like Facebook, LinkedIn, and Yahoo, which converged on using the Web standards as a means to have persistent, authoritative URIs (uniform resource identifiers) that can be shared globally, he suggested to a round of applause.

Another attendee called for future drafts of the Roadmap to address an increasing trend among biopharmaceutical companies to create their own portals or mobile apps for a specific therapy, which requires providers to download multiple infrastructures to support various therapies.

Still another attendee artfully asked that Departments of Defense and Veterans Affairs medical records be incorporated into the proposed nationwide IT system to ensure meaningful longitudinal care for veterans.

There was little audience discussion about the Roadmap’s other core building blocks of a common clinical data set or privacy and security. Concerns about medical device interoperability, however, were raised from the floor and have been echoed in the public comments received by the ONC, Ms. Galvez said.

She stressed that the Roadmap is a shared plan that attempts to capture both public and private sector activities.

“We’re not going to achieve interoperability at the scale we are attempting with government action alone,” Ms. Galvez said. “In looking at some of the early public comments, I will say I have not seen as many commitments from folks as I would really like to see. I’d really like to see organizations coming forward and saying ‘There’s a call to action in this space, we think there’s something we can do about that, and here’s what we’re willing to do.’ ”

The public comment period on the Roadmap officially closed April 3, but comments on the ONC’s 2015 Interoperability Standards Advisory will be accepted through May 1.

[email protected]

SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.

“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.

The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.

The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.

The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.

The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.

An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.

Nick Piegari/Frontline Medical Communications

A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.

Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.

A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.

The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.

[email protected]

SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.

“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.

The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.

The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.

The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.

The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.

An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.

Nick Piegari/Frontline Medical Communications

A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.

Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.

A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.

The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.

[email protected]

SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.

“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.

The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.

The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.

The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.

The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.

An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.

Nick Piegari/Frontline Medical Communications

A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.

Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.

A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.

The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.

[email protected]

SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.

At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.

The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.

“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.

DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.

Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.

Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.

Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.

Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.

Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”

DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.

Mitchel L. Zoler/Frontline Medical News

Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.

There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.

“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”

Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”

“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”

Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.

[email protected]

SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.

At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.

The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.

“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.

DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.

Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.

Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.

Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.

Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.

Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”

DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.

Mitchel L. Zoler/Frontline Medical News

Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.

There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.

“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”

Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”

“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”

Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.

[email protected]

SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.

At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.

The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.

“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.

DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.

Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.

Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.

Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.

Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.

Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”

DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.

Mitchel L. Zoler/Frontline Medical News

Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.

There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.

“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”

Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”

“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”

Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.

[email protected]