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Baricitinib shows potential as lupus treatment
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
AMSTERDAM – A significantly higher proportion of patients with lupus experienced improvements in joint and skin symptoms if they were treated with baricitinib (Olumiant) than if they received placebo in a phase 2 trial.
The primary endpoint of arthritis or rash resolution as measured by the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) was met by approximately 67% of patients who were treated with 4 mg baricitinib once daily and by around 53% of patients given a matching placebo (P less than .05).
With no new safety concerns, these findings suggest that baricitinib could be of benefit in patients with SLE and further study is warranted in a phase 3 trial, said the presenting study investigator Daniel J. Wallace, MD, at the European Congress of Rheumatology. Dr. Wallace is the associate director of the Rheumatology Fellowship Program at Cedars-Sinai Medical Center, Los Angeles.
Baricitinib is already approved for use as a treatment for RA in more than 40 countries. On June 1, Eli Lilly announced that the Food and Drug Administration had given the green light for its use in RA in the United States, but only at a dose of 2 mg once daily, whereas a 2-mg and 4-mg once-daily dose is approved in most other countries.
Data from the phase 2 trial presented by Dr. Wallace did include a 2-mg dose arm, but the difference in treatment response rates versus placebo was not statistically significant.
“I think the placebo response is mainly inflated by the use of corticosteroids,” said Dr. Dörner, professor of medicine at Charité–Universitätsmedizin Berlin. “If one would have applied a steroid tapering regimen, I would have expected a larger effect size, and possibly also the 2-mg [dose] be more effective as compared to placebo.” This is something to consider when moving into a phase 3 trial, he suggested.
For inclusion in the phase 2 trial, patients had to meet the following criteria: Be positive for antinuclear antibodies and/or a positive anti-dsDNA test, have a SLEDAI-2K clinical score of 4 or more, and have active SLEDAI arthritis and/or rash. Patients with severe active lupus nephritis or CNS involvement were excluded.
The mean age of patients was around 44 years, and as might be expected, the study population was predominantly female (99%). Around two-thirds of patients were white, 19% were of Asian descent, and the rest were designated as “other”. The average time to SLE onset was 9.7 years in the placebo group and just over 11 years in the baricitinib arms, with similar SLEDAI-2K scores of about 8-9, about 7-8 tender joints, and about five swollen joints at baseline.
A number of other secondary endpoints were also met by the 4 mg baricitinib group, Dr. Wallace reported. This included the relatively new Lupus Low Disease Activity State, he said, which was met by 38% (n = 27) of patients treated with 4 mg baricitinib, 33% (n = 35) treated with 2 mg baricitinib, and 26% (n = 27) of those given placebo (P less than .05 for the 4-mg dose vs. placebo). There were also numerically fewer SLE flares, including fewer severe flares.
“Some of the other outcomes demonstrated statistical significance: Physician Global Assessment, tender joint count, worst joint pain, and worst pain on a numeric rating scale,” Dr. Wallace said. A trend towards improvement was seen in the swollen joint count, with modest improvement in fatigue.
Treatment-emergent adverse events were seen in around 71%-73% of patients given baricitinib and 65% of patients given placebo. Most were mild or moderate in nature, but serious adverse events did occur in approximately 10% of patients who received baricitinib and in 4% of those who received placebo.
What’s noteworthy, Dr. Dörner said during a press briefing, is the very low rate of venous thromboembolism seen in the trial. “We’d have expected to see more deep vein thrombosis,” he said. Only one case occurred, in a patent taking the 4-mg dose, but this patient had preexisting antiphospholipid antibodies.
Additionally, although the percentage of patients with serious infections was slightly higher in the 2 and 4 mg baricitinib arms than for placebo (1.9% and 5.8% vs. 1%, respectively) “this is what we expect for lupus patients,” Dr. Dörner said. Furthermore, herpes zoster infection, which is very often reactivated in lupus because of the disease or its treatment, was only reported in one patient in the placebo group and in one patient in the 4 mg group.
“I think there is a very promising outlook, at least for the 4-mg dose of baricitinib,” Dr. Dörner said. “There have been no new safety or tolerability issues when compared to the RA population, and we’re looking forward to seeing subsequent studies in this [SLE] patient population where we have a need for more efficacious therapies.”
The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: Baricitinib at 4 mg was associated with significant clinical improvements versus placebo and had an acceptable safety and tolerability profile.
Major finding: A higher percentage of patients receiving 4 mg of baricitinib than those receiving placebo achieved the primary endpoint of arthritis and/or rash remission as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 at week 24 (P less than .05).
Study details: A phase 2, multinational, double-blind, placebo-controlled, parallel group study of once-daily, oral baricitinib (2 mg and 4 mg) in 314 patients with SLE receiving standard therapy.
Disclosures: The study was funded by Eli Lilly. Dr. Dörner was part of the trial’s steering committee and has acted as a consultant for Eli Lilly. He has also received grant or research support from Roche/Chugai, Janssen, and Sanofi-Aventis; consulted for AbbVie, Celgene, Roche, UCB, Merck Sharp & Dohme, Pfizer/Hospira, and Novartis; and he is part of the speakers bureaus for Amgen, Celgene, and Biogen. Dr. Wallace has acted as a consultant for Eli Lilly, as well as EMD Serono, Pfizer, and GlaxoSmithKline.
Source: Wallace DJ et al. Ann Rheum Dis. 2018;77(Suppl 2):59. Abstract OP0019.
PREOPANC-1: Early findings suggest benefit with preop chemo in pancreatic cancer
CHICAGO – Preoperative chemotherapy improves outcomes in patients with resectable or borderline resectable pancreatic cancer, preliminary findings from the phase 3 PREOPANC-1 trial suggest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Overall survival in 127 patients randomized to immediate surgery followed by adjuvant chemotherapy was 13.7 months vs. 17.1 months in 119 patients randomized to receive preoperative chemoradiotherapy and postoperative adjuvant chemotherapy, Geertjan van Tienhoven, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The difference did not quite reach statistical significance, but final analysis requires an additional 26 events, Dr. van Tienhoven of Academic Medical Center, Amsterdam explained in a video interview at the meeting.
Other differences between the groups, which included disease-free survival, local control, and metastasis-free survival, did differ significantly in favor of preoperative chemotherapy, he said.
Of note, 72% and 62% of patients in the immediate surgery and preoperative chemoradiotherapy groups, respectively, underwent resection and a greater proportion of patients in the latter group achieved microscopically complete resection, he said (63% vs. 31%).
Should these results hold up in the final analysis, particularly if the difference in overall survival reaches statistical significance, “then this is a proof of principle and practice-changing trial,” Dr. van Tienhoven said.
Dr. van Tienhoven reported having no disclosures.
SOURCE: van Tienhoven et al. ASCO 2108, Abstract LBA4002.
CHICAGO – Preoperative chemotherapy improves outcomes in patients with resectable or borderline resectable pancreatic cancer, preliminary findings from the phase 3 PREOPANC-1 trial suggest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Overall survival in 127 patients randomized to immediate surgery followed by adjuvant chemotherapy was 13.7 months vs. 17.1 months in 119 patients randomized to receive preoperative chemoradiotherapy and postoperative adjuvant chemotherapy, Geertjan van Tienhoven, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The difference did not quite reach statistical significance, but final analysis requires an additional 26 events, Dr. van Tienhoven of Academic Medical Center, Amsterdam explained in a video interview at the meeting.
Other differences between the groups, which included disease-free survival, local control, and metastasis-free survival, did differ significantly in favor of preoperative chemotherapy, he said.
Of note, 72% and 62% of patients in the immediate surgery and preoperative chemoradiotherapy groups, respectively, underwent resection and a greater proportion of patients in the latter group achieved microscopically complete resection, he said (63% vs. 31%).
Should these results hold up in the final analysis, particularly if the difference in overall survival reaches statistical significance, “then this is a proof of principle and practice-changing trial,” Dr. van Tienhoven said.
Dr. van Tienhoven reported having no disclosures.
SOURCE: van Tienhoven et al. ASCO 2108, Abstract LBA4002.
CHICAGO – Preoperative chemotherapy improves outcomes in patients with resectable or borderline resectable pancreatic cancer, preliminary findings from the phase 3 PREOPANC-1 trial suggest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Overall survival in 127 patients randomized to immediate surgery followed by adjuvant chemotherapy was 13.7 months vs. 17.1 months in 119 patients randomized to receive preoperative chemoradiotherapy and postoperative adjuvant chemotherapy, Geertjan van Tienhoven, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The difference did not quite reach statistical significance, but final analysis requires an additional 26 events, Dr. van Tienhoven of Academic Medical Center, Amsterdam explained in a video interview at the meeting.
Other differences between the groups, which included disease-free survival, local control, and metastasis-free survival, did differ significantly in favor of preoperative chemotherapy, he said.
Of note, 72% and 62% of patients in the immediate surgery and preoperative chemoradiotherapy groups, respectively, underwent resection and a greater proportion of patients in the latter group achieved microscopically complete resection, he said (63% vs. 31%).
Should these results hold up in the final analysis, particularly if the difference in overall survival reaches statistical significance, “then this is a proof of principle and practice-changing trial,” Dr. van Tienhoven said.
Dr. van Tienhoven reported having no disclosures.
SOURCE: van Tienhoven et al. ASCO 2108, Abstract LBA4002.
REPORTING FROM ASCO 2018
John DeLuca, PhD
Four phase 3 studies highlighted at ASCO mark progress in GI cancers
CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.
In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.
The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.
Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.
“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.
The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.
“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.
However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.
“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.
In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].
“With good sound science like this we continue to inch closer to the answers we need,” he concluded.
Dr. Epstein reported having no disclosures.
CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.
In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.
The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.
Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.
“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.
The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.
“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.
However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.
“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.
In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].
“With good sound science like this we continue to inch closer to the answers we need,” he concluded.
Dr. Epstein reported having no disclosures.
CHICAGO – Findings from four recent, phase 3 gastrointestinal cancer studies mark a step forward toward “the answers we need” for patients with pancreatic, colorectal, or esophageal cancer, according to Andrew S. Epstein, MD.
In this video interview, Dr. Epstein summarizes and provides context for the findings, which were presented at the annual meeting of the American Society of Clinical Oncology and highlighted during a press briefing there. Dr. Epstein, an ASCO Expert and a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, who was invited to discuss each of the studies at the briefing, said the UNICANCER-sponsored Prodige 7 trial addressed an important, long-unanswered question about the value of hyperthermic intraperitoneal chemotherapy (HIPEC) with surgery for colorectal peritoneal carcinomatosis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This randomized study, very importantly, answered that longstanding question and showed us in a less-is-more type of way that the addition of the chemotherapy during surgery actually did not improve the overall survival of these patients,” he said, adding that, at 60 days, HIPEC actually had done more harm than good.
The findings are helpful, as HIPEC has been widely used without a solid data foundation, and now the use of an “additional toxic nonbeneficial treatment” can be avoided in a subset of patients.
Two studies regarding chemotherapy in patients with pancreatic cancer also provided important information about treatment. Preliminary data from one, the PREOPANC-1 trial, suggested that perioperative chemoradiotherapy significantly improves outcomes in resectable and borderline resectable patients, compared with immediate surgery; the other – the Prodige 24/CCTG PA.6 trial – demonstrated that adjuvant mFOLFIRINOX, a four-agent regimen, improved disease-free, metastasis-free, and overall survival, with treated patients living a median of 20 months longer and being cancer free for a median of 9 months longer than those who received gemcitabine therapy.
“We saw a very impressive, encouraging, statistically and clinically significant improvement,” he said regarding survival outcomes in Prodige 24. In patients with good performance status who can tolerate the regimen, mFOLFIRINOX “seems to be the way to go now,” he added, noting that patients receiving the regimen require close monitoring by a medical oncologist.
The fourth study, a prevention trial known as the ASPECT trial, showed that high-dose esomeprazole and low-dose aspirin taken for at least 7 years moderately reduces the risk of high-grade dysplasia and esophageal cancer, and may delay death from any cause in patients with Barrett’s esophagus.
“[It is] obviously of huge importance to be able to prevent a cancer before its onset. ... So with esophagus cancer, which also is a very difficult disease to treat in whatever stage it is, it would be a huge benefit to have a way in which to effectively prevent it,” Dr. Epstein said.
However, more information is needed about the actual benefits in terms of all-cause mortality and the contributors from aspirin versus the proton pump inhibitor versus both, he noted, adding that it is important for the public to know that the findings only apply to those with Barrett’s esophagus and shouldn’t be attempted with over-the-counter treatments as some treatments are associated with complications, and the proton pump inhibitor dose used in this study is not available over the counter.
“So I think it is an intriguing study which needs more clarity and more follow-up, as the author himself said,” he added.
In summing up the findings presented at the briefing, Dr. Epstein said that “collectively we see that the challenge of cancer remains significant and we need high-quality studies like the ones presented today in order to best present ...what the best therapies are for [patients].
“With good sound science like this we continue to inch closer to the answers we need,” he concluded.
Dr. Epstein reported having no disclosures.
EXPERT ANALYSIS FROM ASCO 2018
Semaglutide drops HbA1c, weight, across ethnicities
BOSTON – studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).
“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.
The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.
Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.
In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.
An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.
At baseline in all trials, mean hemoglobin A1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.
The range of reductions in HbA1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA1c less than 6.5%, said Dr. Desouza.
Looking at the data another way, 62.2%-72.4% of patients saw an HbA1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.
“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.
Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.
Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”
The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.
SOURCE: Desouza C et al. AACE 2018, Abstract 298
BOSTON – studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).
“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.
The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.
Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.
In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.
An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.
At baseline in all trials, mean hemoglobin A1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.
The range of reductions in HbA1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA1c less than 6.5%, said Dr. Desouza.
Looking at the data another way, 62.2%-72.4% of patients saw an HbA1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.
“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.
Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.
Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”
The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.
SOURCE: Desouza C et al. AACE 2018, Abstract 298
BOSTON – studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).
“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.
The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.
Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.
In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.
An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.
At baseline in all trials, mean hemoglobin A1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.
The range of reductions in HbA1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA1c less than 6.5%, said Dr. Desouza.
Looking at the data another way, 62.2%-72.4% of patients saw an HbA1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.
“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.
Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.
Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”
The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.
SOURCE: Desouza C et al. AACE 2018, Abstract 298
REPORTING FROM AACE 2018
Web portal does not reduce phone encounters or office visits for IBD patients
WASHINGTON – Inflammatory bowel disease patients may love web-based portals that allow them to interact with their doctors and records, but it does not seem to reduce their trips to the doctor.
“There was actually no decrease in office visits or phone encounters with patients that are utilizing MyChart [a web-based patient portal],” said Alexander Hristov, MD, a resident at the University of Wisconsin–Madison, in a video interview at the annual Digestive Disease Week®. “So in fact, the patients that had MyChart use were also the patients that were calling in more frequently and visiting the clinic more frequently, which is interesting because we did not see that there was an offset for emergency room visits or hospitalizations.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Out of the 616 total patients with either Crohn’s disease (355 patients) or ulcerative colitis (261 patients) analyzed in the study, 28% used MyChart. MyChart users also had higher number of prednisone prescriptions, compared with nonusers (51.9% vs. 40.8%, P = .01). There was no difference between MyChart users and nonusers for emergency room visits (P = .11) or hospitalizations (P = .16).
Interestingly, most messages sent via MyChart were for administrative reasons (54%), with both symptoms (28%) and education (18%) lagging behind.
Even though patients seem to like the portal, there is no billable time set aside for physicians to add the data for patients to access or respond to patient comments and requests through the portal. Unless MyChart can be shown to improve outcomes in some way, it is only an added burden for physicians.
Dr. Hristov mentioned that further work should be done to understand how web-based portals like MyChart can help both doctors and patients utilize this technology.
“We want to see the actual, measurable clinical outcomes of MyChart use,” he said. “So we want to set up a protocol where we can actually have measurable statistics looking at disease activity, inflammatory markers, and is there an impact that we are having on the patients disease course.”
Dr. Hristov had no financial disclosures to report.
SOURCE: Hristov A et al. Gastroenterology. 2018 May. doi: 0.1016/S0016-5085(18)32737-9.
WASHINGTON – Inflammatory bowel disease patients may love web-based portals that allow them to interact with their doctors and records, but it does not seem to reduce their trips to the doctor.
“There was actually no decrease in office visits or phone encounters with patients that are utilizing MyChart [a web-based patient portal],” said Alexander Hristov, MD, a resident at the University of Wisconsin–Madison, in a video interview at the annual Digestive Disease Week®. “So in fact, the patients that had MyChart use were also the patients that were calling in more frequently and visiting the clinic more frequently, which is interesting because we did not see that there was an offset for emergency room visits or hospitalizations.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Out of the 616 total patients with either Crohn’s disease (355 patients) or ulcerative colitis (261 patients) analyzed in the study, 28% used MyChart. MyChart users also had higher number of prednisone prescriptions, compared with nonusers (51.9% vs. 40.8%, P = .01). There was no difference between MyChart users and nonusers for emergency room visits (P = .11) or hospitalizations (P = .16).
Interestingly, most messages sent via MyChart were for administrative reasons (54%), with both symptoms (28%) and education (18%) lagging behind.
Even though patients seem to like the portal, there is no billable time set aside for physicians to add the data for patients to access or respond to patient comments and requests through the portal. Unless MyChart can be shown to improve outcomes in some way, it is only an added burden for physicians.
Dr. Hristov mentioned that further work should be done to understand how web-based portals like MyChart can help both doctors and patients utilize this technology.
“We want to see the actual, measurable clinical outcomes of MyChart use,” he said. “So we want to set up a protocol where we can actually have measurable statistics looking at disease activity, inflammatory markers, and is there an impact that we are having on the patients disease course.”
Dr. Hristov had no financial disclosures to report.
SOURCE: Hristov A et al. Gastroenterology. 2018 May. doi: 0.1016/S0016-5085(18)32737-9.
WASHINGTON – Inflammatory bowel disease patients may love web-based portals that allow them to interact with their doctors and records, but it does not seem to reduce their trips to the doctor.
“There was actually no decrease in office visits or phone encounters with patients that are utilizing MyChart [a web-based patient portal],” said Alexander Hristov, MD, a resident at the University of Wisconsin–Madison, in a video interview at the annual Digestive Disease Week®. “So in fact, the patients that had MyChart use were also the patients that were calling in more frequently and visiting the clinic more frequently, which is interesting because we did not see that there was an offset for emergency room visits or hospitalizations.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Out of the 616 total patients with either Crohn’s disease (355 patients) or ulcerative colitis (261 patients) analyzed in the study, 28% used MyChart. MyChart users also had higher number of prednisone prescriptions, compared with nonusers (51.9% vs. 40.8%, P = .01). There was no difference between MyChart users and nonusers for emergency room visits (P = .11) or hospitalizations (P = .16).
Interestingly, most messages sent via MyChart were for administrative reasons (54%), with both symptoms (28%) and education (18%) lagging behind.
Even though patients seem to like the portal, there is no billable time set aside for physicians to add the data for patients to access or respond to patient comments and requests through the portal. Unless MyChart can be shown to improve outcomes in some way, it is only an added burden for physicians.
Dr. Hristov mentioned that further work should be done to understand how web-based portals like MyChart can help both doctors and patients utilize this technology.
“We want to see the actual, measurable clinical outcomes of MyChart use,” he said. “So we want to set up a protocol where we can actually have measurable statistics looking at disease activity, inflammatory markers, and is there an impact that we are having on the patients disease course.”
Dr. Hristov had no financial disclosures to report.
SOURCE: Hristov A et al. Gastroenterology. 2018 May. doi: 0.1016/S0016-5085(18)32737-9.
REPORTING FROM DDW 2018
Key clinical point: Inflammatory bowel disease patients had more office visits and phone calls with physicians, and had worse outcomes.
Major finding: MyChart patients averaged 7.2 office visits and 19.2 phone encounters, compared with 5.6 office visits and 13.7 phone encounters in nonusers.
Study details: A review of patient electronic health records from Jan. 1, 2012, to December 31, 2015.
Disclosures: Dr. Hristov had no relevant financial disclosures to report.
Source: Hristov A et al Gastroenterology. 2018 May. doi: 10.1016/S0016-5085(18)32737-9.
VIDEO: Hepatitis C eradication cuts nonliver cancer rate
WASHINGTON – Treatment of hepatitis C infection with a direct-acting antiviral drug strongly linked with a rapid, 14% drop in the incidence of all nonhepatic cancers, based on analysis of data from more than 30,000 U.S. patients.
The data also showed compared with infected patients who had been treated with an interferon-based regimen during the period immediately preceding the availability of DAAs in late 2013. This included a 45% cut in lung cancers, a 49% cut in bladder cancer, a 62% relative risk reduction in leukemia, and a 29% drop in prostate cancer, Michael B. Charlton, MD, said at the annual Digestive Disease Week.®
The relative reductions in nonhepatic cancer incidence appeared soon after DAA treatment. The data Dr. Charlton reported reflected a median follow-up of 1 year for DAA-treated patients and 2.6 years for the hepatitis C–infected patients who had received interferon and did not get a DAA. A major difference between these two regimens is their efficacy, with DAA regimens producing sustained virologic response rates of 90% or better, while the interferon regimens produced substantially lower eradication rates.
“The most obvious hypothesis” to explain the observed effects is that “hepatitis C is a potent carcinogen,” possibly acting by inhibiting immune surveillance for new cancers in infected people, Dr. Charlton said in a video interview.
The study he reported used insurance-claims data from more than 146 million U.S. residents during 2007-2017 in the IQVIA PharMetrics Plus database, which included more than 367,000 adults infected with hepatitis C. Dr. Charlton and his associates pulled from this claims data on 10,989 of the infected patients who received interferon during January 2007-May 2011 (and followed through November 2013), and 22,894 infected patients treated with any type of DAA during December 2013 through March 2017. They used these two discrete time windows to completely separate the patients who received a DAA from those who did not.
The primary analysis calculated a hazard ratio for the development of any nonhepatic cancer after adjustment for a number of demographic and clinical covariates including age, smoking history, and weight, and also applied propensity-score weighting to the data. The Kaplan-Meier analysis of the data showed clear separation of the cancer-free survival curves of the two subgroups by 6 months of follow-up, and then showed steady further separation over time suggesting an ongoing carcinogenic effect from continued hepatitis C infection in patients who had received the less effective antiviral regimen. The analysis was able to reveal this effect because it had data from many thousands of treated hepatitis C patients, far more than had been enrolled in the pivotal trials for the DAAs, noted Dr. Charlton, professor and director of the Center for Liver Diseases at the University of Chicago.
The Centers for Disease Control and Prevention estimates that 3.5 million Americans have a chronic hepatitis C infection. Dr. Charlton believed the number today might be more like 1-2 million remaining chronic U.S. cases because of the strong impact of DAA treatment. These chronic infections largely remain because hepatitis C is mostly silent and many clinicians fail to act on screening recommendations. The new findings provide even greater incentive for more rigorous screening and treatment, Dr. Charlton suggested.
“As if you needed another reason to get rid of hepatitis C, lowering your cancer risk is now added to the list,” he said.
WASHINGTON – Treatment of hepatitis C infection with a direct-acting antiviral drug strongly linked with a rapid, 14% drop in the incidence of all nonhepatic cancers, based on analysis of data from more than 30,000 U.S. patients.
The data also showed compared with infected patients who had been treated with an interferon-based regimen during the period immediately preceding the availability of DAAs in late 2013. This included a 45% cut in lung cancers, a 49% cut in bladder cancer, a 62% relative risk reduction in leukemia, and a 29% drop in prostate cancer, Michael B. Charlton, MD, said at the annual Digestive Disease Week.®
The relative reductions in nonhepatic cancer incidence appeared soon after DAA treatment. The data Dr. Charlton reported reflected a median follow-up of 1 year for DAA-treated patients and 2.6 years for the hepatitis C–infected patients who had received interferon and did not get a DAA. A major difference between these two regimens is their efficacy, with DAA regimens producing sustained virologic response rates of 90% or better, while the interferon regimens produced substantially lower eradication rates.
“The most obvious hypothesis” to explain the observed effects is that “hepatitis C is a potent carcinogen,” possibly acting by inhibiting immune surveillance for new cancers in infected people, Dr. Charlton said in a video interview.
The study he reported used insurance-claims data from more than 146 million U.S. residents during 2007-2017 in the IQVIA PharMetrics Plus database, which included more than 367,000 adults infected with hepatitis C. Dr. Charlton and his associates pulled from this claims data on 10,989 of the infected patients who received interferon during January 2007-May 2011 (and followed through November 2013), and 22,894 infected patients treated with any type of DAA during December 2013 through March 2017. They used these two discrete time windows to completely separate the patients who received a DAA from those who did not.
The primary analysis calculated a hazard ratio for the development of any nonhepatic cancer after adjustment for a number of demographic and clinical covariates including age, smoking history, and weight, and also applied propensity-score weighting to the data. The Kaplan-Meier analysis of the data showed clear separation of the cancer-free survival curves of the two subgroups by 6 months of follow-up, and then showed steady further separation over time suggesting an ongoing carcinogenic effect from continued hepatitis C infection in patients who had received the less effective antiviral regimen. The analysis was able to reveal this effect because it had data from many thousands of treated hepatitis C patients, far more than had been enrolled in the pivotal trials for the DAAs, noted Dr. Charlton, professor and director of the Center for Liver Diseases at the University of Chicago.
The Centers for Disease Control and Prevention estimates that 3.5 million Americans have a chronic hepatitis C infection. Dr. Charlton believed the number today might be more like 1-2 million remaining chronic U.S. cases because of the strong impact of DAA treatment. These chronic infections largely remain because hepatitis C is mostly silent and many clinicians fail to act on screening recommendations. The new findings provide even greater incentive for more rigorous screening and treatment, Dr. Charlton suggested.
“As if you needed another reason to get rid of hepatitis C, lowering your cancer risk is now added to the list,” he said.
WASHINGTON – Treatment of hepatitis C infection with a direct-acting antiviral drug strongly linked with a rapid, 14% drop in the incidence of all nonhepatic cancers, based on analysis of data from more than 30,000 U.S. patients.
The data also showed compared with infected patients who had been treated with an interferon-based regimen during the period immediately preceding the availability of DAAs in late 2013. This included a 45% cut in lung cancers, a 49% cut in bladder cancer, a 62% relative risk reduction in leukemia, and a 29% drop in prostate cancer, Michael B. Charlton, MD, said at the annual Digestive Disease Week.®
The relative reductions in nonhepatic cancer incidence appeared soon after DAA treatment. The data Dr. Charlton reported reflected a median follow-up of 1 year for DAA-treated patients and 2.6 years for the hepatitis C–infected patients who had received interferon and did not get a DAA. A major difference between these two regimens is their efficacy, with DAA regimens producing sustained virologic response rates of 90% or better, while the interferon regimens produced substantially lower eradication rates.
“The most obvious hypothesis” to explain the observed effects is that “hepatitis C is a potent carcinogen,” possibly acting by inhibiting immune surveillance for new cancers in infected people, Dr. Charlton said in a video interview.
The study he reported used insurance-claims data from more than 146 million U.S. residents during 2007-2017 in the IQVIA PharMetrics Plus database, which included more than 367,000 adults infected with hepatitis C. Dr. Charlton and his associates pulled from this claims data on 10,989 of the infected patients who received interferon during January 2007-May 2011 (and followed through November 2013), and 22,894 infected patients treated with any type of DAA during December 2013 through March 2017. They used these two discrete time windows to completely separate the patients who received a DAA from those who did not.
The primary analysis calculated a hazard ratio for the development of any nonhepatic cancer after adjustment for a number of demographic and clinical covariates including age, smoking history, and weight, and also applied propensity-score weighting to the data. The Kaplan-Meier analysis of the data showed clear separation of the cancer-free survival curves of the two subgroups by 6 months of follow-up, and then showed steady further separation over time suggesting an ongoing carcinogenic effect from continued hepatitis C infection in patients who had received the less effective antiviral regimen. The analysis was able to reveal this effect because it had data from many thousands of treated hepatitis C patients, far more than had been enrolled in the pivotal trials for the DAAs, noted Dr. Charlton, professor and director of the Center for Liver Diseases at the University of Chicago.
The Centers for Disease Control and Prevention estimates that 3.5 million Americans have a chronic hepatitis C infection. Dr. Charlton believed the number today might be more like 1-2 million remaining chronic U.S. cases because of the strong impact of DAA treatment. These chronic infections largely remain because hepatitis C is mostly silent and many clinicians fail to act on screening recommendations. The new findings provide even greater incentive for more rigorous screening and treatment, Dr. Charlton suggested.
“As if you needed another reason to get rid of hepatitis C, lowering your cancer risk is now added to the list,” he said.
REPORTING FROM DDW 2018
Key clinical point: Eradicating hepatitis C with direct-acting antivirals significantly cut the incidence of many nonliver cancers.
Major finding: Direct-acting antiviral treatment linked with a 14% drop in nonhepatic cancers, compared with patients not getting this treatment.
Study details: Analysis of 33,883 Americans treated for hepatitis C during 2007-2017 in an insurance claims database.
Disclosures: The study was funded by Gilead, a company that markets direct-acting antiviral drugs for hepatitis C virus. Dr. Charlton has been a consultant to and has received research funding from Gilead and several other companies that market drugs from this class.
Atopic Dermatitis and Peanut Allergy Prevention: New Guidelines
A Peek at Our June 2018 Issue
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. William J. Gradishar shares breast cancer take-aways from ASCO 2018
CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.
Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”
CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.
Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”
CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.
In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.
Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”
REPORTING FROM ASCO 2018
