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First-in-class glutaminase inhibitor combats anti-PD-1/PD-L1 resistance
NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.
Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.
Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.
In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).
During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.
Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.
Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.
“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.
In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.
A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.
In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).
“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.
The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.
“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.
Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.
NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.
Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.
Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.
In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).
During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.
Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.
Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.
“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.
In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.
A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.
In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).
“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.
The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.
“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.
Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.
NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.
Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.
Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.
In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).
During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.
Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.
Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.
“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.
In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.
A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.
In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).
“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.
The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.
“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.
Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.
AT SITC 2017
Key clinical point:
Major finding: The objective response rate in advanced melanoma patients refractory to anti-PD-1/PD-L1 therapy was 19%.
Data source: A phase 1/2 study of 82 patients.
Disclosures: Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel or as a board member for multiple companies.
Pancreatic surgery: Similar outcomes with primary anastomosis, allografts
Pancreatic tumor involvement with the superior mesenteric vein/portal vein (SMV/PV) is common and requires exploration and resection, which has now become an integral part of routine surgical treatment. The short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts was found to be comparable to that of reconstruction with primary end-to-end anastomosis, according to the results of a study performed by Dyre Kleive, MD, and his colleagues.
In order to assess the optimal method of reconstructing the portal vein during pancreatic surgery, Dr. Kleive and his colleagues performed a retrospective review of all patients undergoing pancreatic surgery with venous resection and reconstruction at a single center between January 2006 and December 2015.
A total of 857 patients underwent open pancreatic surgery during the study period, of whom 171 (20%) had vascular resection and reconstruction. The study population comprised 42 patients treated with cold-stored interposition cadaveric allografts for reconstruction and 71 patients who had primary end-to-end anastomosis instead. Patients with other forms of reconstruction were excluded, according to an online report in the Journal of Vascular Surgery: Venous and Lymphatic Disorders (2017. doi: 10.1016/j.jvsv.2017.09.003).
Early failure at the reconstruction site was defined as the presence of thrombosis or no flow or low flow within the first 30 days after surgery.
Patients in the allograft group had statistically significantly longer mean operative times, more intraoperative bleeding, more frequent use of neoadjuvant therapy, and a longer length of tumor-vein involvement than the anastomosis group.
However, there was no statistically significant difference in the number of patients with major complications (42.9% for allografts vs. 36.6% for anastomosis) or early failure at the reconstruction site (9.5% for allografts vs. 8.5% for anastomosis) between the two groups, Dr Kleive and his colleagues reported.
The proportion of patients with grade C stenosis at last available imaging scan was significantly higher in the allograft group (26/42 [61.9%] vs. 13 of 66 [19.7%] for the anastomosis group; P less than .01). A subgroup analysis of 10 patients in the allograft group showed the presence of donor-specific antibodies in all patients. This could indicate that graft rejection was a contributing factor to the statistically higher development of severe stenosis in allograft vs. anastomosis patients, the authors suggested.
“This study shows that the short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts is comparable to that of reconstruction with primary end-to-end anastomosis,” the researchers concluded.
Dr. Kleive and his colleagues reported that they had no conflicts of interest.
Pancreatic tumor involvement with the superior mesenteric vein/portal vein (SMV/PV) is common and requires exploration and resection, which has now become an integral part of routine surgical treatment. The short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts was found to be comparable to that of reconstruction with primary end-to-end anastomosis, according to the results of a study performed by Dyre Kleive, MD, and his colleagues.
In order to assess the optimal method of reconstructing the portal vein during pancreatic surgery, Dr. Kleive and his colleagues performed a retrospective review of all patients undergoing pancreatic surgery with venous resection and reconstruction at a single center between January 2006 and December 2015.
A total of 857 patients underwent open pancreatic surgery during the study period, of whom 171 (20%) had vascular resection and reconstruction. The study population comprised 42 patients treated with cold-stored interposition cadaveric allografts for reconstruction and 71 patients who had primary end-to-end anastomosis instead. Patients with other forms of reconstruction were excluded, according to an online report in the Journal of Vascular Surgery: Venous and Lymphatic Disorders (2017. doi: 10.1016/j.jvsv.2017.09.003).
Early failure at the reconstruction site was defined as the presence of thrombosis or no flow or low flow within the first 30 days after surgery.
Patients in the allograft group had statistically significantly longer mean operative times, more intraoperative bleeding, more frequent use of neoadjuvant therapy, and a longer length of tumor-vein involvement than the anastomosis group.
However, there was no statistically significant difference in the number of patients with major complications (42.9% for allografts vs. 36.6% for anastomosis) or early failure at the reconstruction site (9.5% for allografts vs. 8.5% for anastomosis) between the two groups, Dr Kleive and his colleagues reported.
The proportion of patients with grade C stenosis at last available imaging scan was significantly higher in the allograft group (26/42 [61.9%] vs. 13 of 66 [19.7%] for the anastomosis group; P less than .01). A subgroup analysis of 10 patients in the allograft group showed the presence of donor-specific antibodies in all patients. This could indicate that graft rejection was a contributing factor to the statistically higher development of severe stenosis in allograft vs. anastomosis patients, the authors suggested.
“This study shows that the short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts is comparable to that of reconstruction with primary end-to-end anastomosis,” the researchers concluded.
Dr. Kleive and his colleagues reported that they had no conflicts of interest.
Pancreatic tumor involvement with the superior mesenteric vein/portal vein (SMV/PV) is common and requires exploration and resection, which has now become an integral part of routine surgical treatment. The short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts was found to be comparable to that of reconstruction with primary end-to-end anastomosis, according to the results of a study performed by Dyre Kleive, MD, and his colleagues.
In order to assess the optimal method of reconstructing the portal vein during pancreatic surgery, Dr. Kleive and his colleagues performed a retrospective review of all patients undergoing pancreatic surgery with venous resection and reconstruction at a single center between January 2006 and December 2015.
A total of 857 patients underwent open pancreatic surgery during the study period, of whom 171 (20%) had vascular resection and reconstruction. The study population comprised 42 patients treated with cold-stored interposition cadaveric allografts for reconstruction and 71 patients who had primary end-to-end anastomosis instead. Patients with other forms of reconstruction were excluded, according to an online report in the Journal of Vascular Surgery: Venous and Lymphatic Disorders (2017. doi: 10.1016/j.jvsv.2017.09.003).
Early failure at the reconstruction site was defined as the presence of thrombosis or no flow or low flow within the first 30 days after surgery.
Patients in the allograft group had statistically significantly longer mean operative times, more intraoperative bleeding, more frequent use of neoadjuvant therapy, and a longer length of tumor-vein involvement than the anastomosis group.
However, there was no statistically significant difference in the number of patients with major complications (42.9% for allografts vs. 36.6% for anastomosis) or early failure at the reconstruction site (9.5% for allografts vs. 8.5% for anastomosis) between the two groups, Dr Kleive and his colleagues reported.
The proportion of patients with grade C stenosis at last available imaging scan was significantly higher in the allograft group (26/42 [61.9%] vs. 13 of 66 [19.7%] for the anastomosis group; P less than .01). A subgroup analysis of 10 patients in the allograft group showed the presence of donor-specific antibodies in all patients. This could indicate that graft rejection was a contributing factor to the statistically higher development of severe stenosis in allograft vs. anastomosis patients, the authors suggested.
“This study shows that the short-term outcome of SMV/PV reconstruction with interposed cold-stored cadaveric venous allografts is comparable to that of reconstruction with primary end-to-end anastomosis,” the researchers concluded.
Dr. Kleive and his colleagues reported that they had no conflicts of interest.
FROM THE JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISEASES
Key clinical point:
Major finding: There was no statistically significant difference in the number of patients with major complications or early failure at the reconstruction site between the allograft and the anastomosis groups.
Data source: A retrospective review of all 171 patients undergoing pancreatic surgery with venous resection and reconstruction at a single center between January 2006 and December 2015.
Disclosures: The authors reported that they had no conflicts of interest.
Bare metal stents: Rest in peace
DENVER – Percutaneous coronary intervention using a contemporary drug-eluting stent on a shortened regimen of dual antiplatelet therapy proved significantly more effective and equally safe as a bare metal stent in elderly patients in the randomized, multicenter SENIOR trial.
“I think BMS [bare metal stents] should no longer be used as a strategy to reduce DAPT [dual antiplatelet therapy] duration in the elderly,” Olivier Varenne, MD, concluded in presenting the SENIOR findings at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
“This trial adds to what I think is now a very large body of evidence showing that DES [drug-eluting stents] are the way to go, pretty much across the board, putting aside the economic factors that might come into play in certain regions of the world,” Deepak L. Bhatt, MD, commented at the meeting sponsored by the Cardiovascular Research Foundation.
“I think in general there’s really no good reason to use a BMS. I’d use a DES. I think DES is a winning strategy, whether it’s for a thrombotic lesion or an older patient,” added Dr. Bhatt, professor of medicine at Harvard Medical School in Boston and executive director of international cardiovascular programs at Brigham and Women’s Hospital.
Martin B. Leon, MD, concurred.
“I cannot think of any indication for using a BMS anymore, other than cost considerations. I think this study is yet another nail in the coffin of BMS. I think they should be relegated to the past because they really have very little role in environments where DES – which are becoming much more cost-efficient – can be used,” said Dr. Leon, professor of medicine at Columbia University and director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Medical Center, New York. Yet in contemporary practice many cardiologists turn to BMS for percutaneous coronary intervention (PCI) in elderly patients with coronary artery disease (CAD), reasoning that the shorter DAPT duration recommended for BMS in the practice guidelines is attractive as a means of minimizing the risk of bleeding complications, which is typically high in the elderly.
The SENIOR trial demonstrates that using a modern DES in combination with the shortened 1- or 6-month DAPT duration typically reserved for BMS recipients results in fewer major adverse cardiac and cerebrovascular events with no increase in bleeding, compared with BMS. This is a finding of high clinical relevance because so many elderly patients undergo PCI; indeed, today one in four PCI patients in the United States is over age 75, explained Dr. Varenne of Cochin Hospital in Paris.
SENIOR was a single-blind, randomized trial of 1,200 PCI patients age 75 and older at 44 centers in nine countries. Their mean age was 81.4 years. This was essentially an all-comers trial: 45% of participants had an acute coronary syndrome, 55% had stable or silent CAD. If they had stable CAD, they were slated for 1 month of DAPT. If they had ACS, they got 6 months of DAPT. All participants were then randomized to PCI with either the thin-strut everolimus-eluting bioabsorbable polymer Synergy DES or the thin-strut Omega or Rebel BMS.
The primary composite efficacy endpoint was the 1-year rate of all-cause mortality, acute MI, stroke, or ischemia-driven target lesion revascularization. The rate was 11.6% in the DES group and 16.4% in the BMS group, for a 29% reduction in favor of the DES strategy and a favorably low number-needed-to-treat of 21. The difference in outcome was driven mainly by a higher ischemia-driven target lesion revascularization rate in the BMS group.
The 1-year rate of bleeding complications was 5% in each group. Probable or definite stent thrombosis occurred in 0.5% of the DES group and 1.4% of the BMS group at 1 year. Ten of the 11 cases of stent thrombosis in the study occurred during the first 30 days after PCI while the patients were on DAPT; the other case occurred on day 31, the day after DAPT was stopped.
Discussant Eric D. Peterson, MD, applauded Dr. Varenne and his coinvestigators for conducting a study focused on elderly individuals, an understudied population largely excluded from the landmark clinical trials in interventional cardiology.
He found the study convincing: “My takeaway is DES is better than BMS. As it is in young people, it continues in old.”
But the study leaves two important questions unanswered: Is the Synergy stent the best DES in the elderly, and what is the best duration of DAPT therapy? Ideally, the SENIOR trial would have included a study arm with the standard 6- and 12-month DAPT durations recommended in the American guidelines for DES recipients with stable and unstable CAD, respectively, observed Dr. Peterson, professor of medicine at Duke University in Durham, N.C., and director of the Duke Clinical Research Institute.
Dr. Varenne replied that SENIOR wasn’t designed as a DAPT duration trial. DAPT duration wasn’t randomized. But other planned and ongoing studies are attempting to define the best DAPT durations in various patient subsets.
Dr. Bhatt said he believes the superiority of contemporary DES over modern BMS is a class effect.
The SENIOR trial was funded by Boston Scientific. Dr. Varenne reported receiving lecture fees from that company as well as Abbott Vascular, AstraZeneca, and Servier within the past year.
DENVER – Percutaneous coronary intervention using a contemporary drug-eluting stent on a shortened regimen of dual antiplatelet therapy proved significantly more effective and equally safe as a bare metal stent in elderly patients in the randomized, multicenter SENIOR trial.
“I think BMS [bare metal stents] should no longer be used as a strategy to reduce DAPT [dual antiplatelet therapy] duration in the elderly,” Olivier Varenne, MD, concluded in presenting the SENIOR findings at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
“This trial adds to what I think is now a very large body of evidence showing that DES [drug-eluting stents] are the way to go, pretty much across the board, putting aside the economic factors that might come into play in certain regions of the world,” Deepak L. Bhatt, MD, commented at the meeting sponsored by the Cardiovascular Research Foundation.
“I think in general there’s really no good reason to use a BMS. I’d use a DES. I think DES is a winning strategy, whether it’s for a thrombotic lesion or an older patient,” added Dr. Bhatt, professor of medicine at Harvard Medical School in Boston and executive director of international cardiovascular programs at Brigham and Women’s Hospital.
Martin B. Leon, MD, concurred.
“I cannot think of any indication for using a BMS anymore, other than cost considerations. I think this study is yet another nail in the coffin of BMS. I think they should be relegated to the past because they really have very little role in environments where DES – which are becoming much more cost-efficient – can be used,” said Dr. Leon, professor of medicine at Columbia University and director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Medical Center, New York. Yet in contemporary practice many cardiologists turn to BMS for percutaneous coronary intervention (PCI) in elderly patients with coronary artery disease (CAD), reasoning that the shorter DAPT duration recommended for BMS in the practice guidelines is attractive as a means of minimizing the risk of bleeding complications, which is typically high in the elderly.
The SENIOR trial demonstrates that using a modern DES in combination with the shortened 1- or 6-month DAPT duration typically reserved for BMS recipients results in fewer major adverse cardiac and cerebrovascular events with no increase in bleeding, compared with BMS. This is a finding of high clinical relevance because so many elderly patients undergo PCI; indeed, today one in four PCI patients in the United States is over age 75, explained Dr. Varenne of Cochin Hospital in Paris.
SENIOR was a single-blind, randomized trial of 1,200 PCI patients age 75 and older at 44 centers in nine countries. Their mean age was 81.4 years. This was essentially an all-comers trial: 45% of participants had an acute coronary syndrome, 55% had stable or silent CAD. If they had stable CAD, they were slated for 1 month of DAPT. If they had ACS, they got 6 months of DAPT. All participants were then randomized to PCI with either the thin-strut everolimus-eluting bioabsorbable polymer Synergy DES or the thin-strut Omega or Rebel BMS.
The primary composite efficacy endpoint was the 1-year rate of all-cause mortality, acute MI, stroke, or ischemia-driven target lesion revascularization. The rate was 11.6% in the DES group and 16.4% in the BMS group, for a 29% reduction in favor of the DES strategy and a favorably low number-needed-to-treat of 21. The difference in outcome was driven mainly by a higher ischemia-driven target lesion revascularization rate in the BMS group.
The 1-year rate of bleeding complications was 5% in each group. Probable or definite stent thrombosis occurred in 0.5% of the DES group and 1.4% of the BMS group at 1 year. Ten of the 11 cases of stent thrombosis in the study occurred during the first 30 days after PCI while the patients were on DAPT; the other case occurred on day 31, the day after DAPT was stopped.
Discussant Eric D. Peterson, MD, applauded Dr. Varenne and his coinvestigators for conducting a study focused on elderly individuals, an understudied population largely excluded from the landmark clinical trials in interventional cardiology.
He found the study convincing: “My takeaway is DES is better than BMS. As it is in young people, it continues in old.”
But the study leaves two important questions unanswered: Is the Synergy stent the best DES in the elderly, and what is the best duration of DAPT therapy? Ideally, the SENIOR trial would have included a study arm with the standard 6- and 12-month DAPT durations recommended in the American guidelines for DES recipients with stable and unstable CAD, respectively, observed Dr. Peterson, professor of medicine at Duke University in Durham, N.C., and director of the Duke Clinical Research Institute.
Dr. Varenne replied that SENIOR wasn’t designed as a DAPT duration trial. DAPT duration wasn’t randomized. But other planned and ongoing studies are attempting to define the best DAPT durations in various patient subsets.
Dr. Bhatt said he believes the superiority of contemporary DES over modern BMS is a class effect.
The SENIOR trial was funded by Boston Scientific. Dr. Varenne reported receiving lecture fees from that company as well as Abbott Vascular, AstraZeneca, and Servier within the past year.
DENVER – Percutaneous coronary intervention using a contemporary drug-eluting stent on a shortened regimen of dual antiplatelet therapy proved significantly more effective and equally safe as a bare metal stent in elderly patients in the randomized, multicenter SENIOR trial.
“I think BMS [bare metal stents] should no longer be used as a strategy to reduce DAPT [dual antiplatelet therapy] duration in the elderly,” Olivier Varenne, MD, concluded in presenting the SENIOR findings at the Transcatheter Cardiovascular Therapeutics annual educational meeting.
“This trial adds to what I think is now a very large body of evidence showing that DES [drug-eluting stents] are the way to go, pretty much across the board, putting aside the economic factors that might come into play in certain regions of the world,” Deepak L. Bhatt, MD, commented at the meeting sponsored by the Cardiovascular Research Foundation.
“I think in general there’s really no good reason to use a BMS. I’d use a DES. I think DES is a winning strategy, whether it’s for a thrombotic lesion or an older patient,” added Dr. Bhatt, professor of medicine at Harvard Medical School in Boston and executive director of international cardiovascular programs at Brigham and Women’s Hospital.
Martin B. Leon, MD, concurred.
“I cannot think of any indication for using a BMS anymore, other than cost considerations. I think this study is yet another nail in the coffin of BMS. I think they should be relegated to the past because they really have very little role in environments where DES – which are becoming much more cost-efficient – can be used,” said Dr. Leon, professor of medicine at Columbia University and director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Medical Center, New York. Yet in contemporary practice many cardiologists turn to BMS for percutaneous coronary intervention (PCI) in elderly patients with coronary artery disease (CAD), reasoning that the shorter DAPT duration recommended for BMS in the practice guidelines is attractive as a means of minimizing the risk of bleeding complications, which is typically high in the elderly.
The SENIOR trial demonstrates that using a modern DES in combination with the shortened 1- or 6-month DAPT duration typically reserved for BMS recipients results in fewer major adverse cardiac and cerebrovascular events with no increase in bleeding, compared with BMS. This is a finding of high clinical relevance because so many elderly patients undergo PCI; indeed, today one in four PCI patients in the United States is over age 75, explained Dr. Varenne of Cochin Hospital in Paris.
SENIOR was a single-blind, randomized trial of 1,200 PCI patients age 75 and older at 44 centers in nine countries. Their mean age was 81.4 years. This was essentially an all-comers trial: 45% of participants had an acute coronary syndrome, 55% had stable or silent CAD. If they had stable CAD, they were slated for 1 month of DAPT. If they had ACS, they got 6 months of DAPT. All participants were then randomized to PCI with either the thin-strut everolimus-eluting bioabsorbable polymer Synergy DES or the thin-strut Omega or Rebel BMS.
The primary composite efficacy endpoint was the 1-year rate of all-cause mortality, acute MI, stroke, or ischemia-driven target lesion revascularization. The rate was 11.6% in the DES group and 16.4% in the BMS group, for a 29% reduction in favor of the DES strategy and a favorably low number-needed-to-treat of 21. The difference in outcome was driven mainly by a higher ischemia-driven target lesion revascularization rate in the BMS group.
The 1-year rate of bleeding complications was 5% in each group. Probable or definite stent thrombosis occurred in 0.5% of the DES group and 1.4% of the BMS group at 1 year. Ten of the 11 cases of stent thrombosis in the study occurred during the first 30 days after PCI while the patients were on DAPT; the other case occurred on day 31, the day after DAPT was stopped.
Discussant Eric D. Peterson, MD, applauded Dr. Varenne and his coinvestigators for conducting a study focused on elderly individuals, an understudied population largely excluded from the landmark clinical trials in interventional cardiology.
He found the study convincing: “My takeaway is DES is better than BMS. As it is in young people, it continues in old.”
But the study leaves two important questions unanswered: Is the Synergy stent the best DES in the elderly, and what is the best duration of DAPT therapy? Ideally, the SENIOR trial would have included a study arm with the standard 6- and 12-month DAPT durations recommended in the American guidelines for DES recipients with stable and unstable CAD, respectively, observed Dr. Peterson, professor of medicine at Duke University in Durham, N.C., and director of the Duke Clinical Research Institute.
Dr. Varenne replied that SENIOR wasn’t designed as a DAPT duration trial. DAPT duration wasn’t randomized. But other planned and ongoing studies are attempting to define the best DAPT durations in various patient subsets.
Dr. Bhatt said he believes the superiority of contemporary DES over modern BMS is a class effect.
The SENIOR trial was funded by Boston Scientific. Dr. Varenne reported receiving lecture fees from that company as well as Abbott Vascular, AstraZeneca, and Servier within the past year.
AT TCT 2017
Key clinical point:
Major finding: The number of elderly patients with CAD who would need to be treated with a contemporary drug-eluting stent backed by a shortened DAPT regimen instead of a modern-era bare metal stent in order to avoid one additional major adverse cardiac and cerebrovascular event over the course of a year is 21.
Data source: This randomized, prospective, single-blind trial included 1,200 patients age 75 or older who underwent PCI at 44 centers in nine countries.
Disclosures: The SENIOR trial was funded by Boston Scientific. The presenter reported receiving lecture fees from that company as well as Abbott Vascular, AstraZeneca, and Servier within the past year.
New buprenorphine formulation approved for medication-assisted treatment
The Food and Drug Administration has approved an extended-release, subcutaneous injection formulation of buprenorphine for use in treating moderate to severe opioid use disorder (OUD), the manufacturer of the drug announced Nov. 30.
The new product, called Sublocade, is a monthly injection intended for use in patients who have already begun treatment of OUD with transmucosal buprenorphine products, followed by a dose adjustment for a minimum of 7 days. Sublocade contains the partial mu-opioid agonist buprenorphine. By administering a consistent level of buprenorphine into the body, it ensures that levels of buprenorphine are delivered to the mu-opioid receptors, diminishing the effects of opioids, including the euphoric sensations associated with opioid use. During the clinical trial program, buprenorphine plasma concentrations of 2-3 ng/mL were found to bind to greater than 70% of mu-opioid receptors.
According to a statement from the FDA, Sublocade will be distributed only to health care providers as part of a Risk Evaluation and Mitigation Strategy to ensure that the product is not distributed directly to patients. Sublocade should be administered only by a health care professional. Self-injection of Sublocade into the blood stream instead of subcutaneously could lead to occlusion of blood vessels and embolism, according to one of the drug’s boxed warnings. It also should be used as part of a complete treatment program that includes counseling and psychosocial support.
The FDA is also requiring the manufacturer to conduct postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once monthly, and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first 2 months of treatment.
At recent joint meetings of the FDA’s Psychopharmacologic Drugs and Drug Safety and Risk Management advisory committees, panelists voted on Oct. 31 to recommend approval of Sublocade and on Nov. 1 for another subcutaneous buprenorphine injection formulation. These actions have not gone unnoticed by the American Medical Association.
“The AMA enthusiastically supports Food and Drug Administration Commissioner Scott Gottlieb’s efforts to advance policies and actions to treat those suffering from an opioid use disorder,” Patrice Harris, MD, immediate past chair of the American Medical Association Board of Trustees and a member of the AMA Opioid Task Force, said in a statement. “We also second his bold acknowledgment that criminal justice systems should offer [medication-assisted treatment] to those being detained. As he points out, ‘At the very moment when the criminal justice system could be dramatically lowering the risk of overdose, it is creating the conditions of reduced tolerance to opioids that substantially raises the risk of death upon release.’ With his clear explanation of the problem and solution, this situation can be remedied.”
The Food and Drug Administration has approved an extended-release, subcutaneous injection formulation of buprenorphine for use in treating moderate to severe opioid use disorder (OUD), the manufacturer of the drug announced Nov. 30.
The new product, called Sublocade, is a monthly injection intended for use in patients who have already begun treatment of OUD with transmucosal buprenorphine products, followed by a dose adjustment for a minimum of 7 days. Sublocade contains the partial mu-opioid agonist buprenorphine. By administering a consistent level of buprenorphine into the body, it ensures that levels of buprenorphine are delivered to the mu-opioid receptors, diminishing the effects of opioids, including the euphoric sensations associated with opioid use. During the clinical trial program, buprenorphine plasma concentrations of 2-3 ng/mL were found to bind to greater than 70% of mu-opioid receptors.
According to a statement from the FDA, Sublocade will be distributed only to health care providers as part of a Risk Evaluation and Mitigation Strategy to ensure that the product is not distributed directly to patients. Sublocade should be administered only by a health care professional. Self-injection of Sublocade into the blood stream instead of subcutaneously could lead to occlusion of blood vessels and embolism, according to one of the drug’s boxed warnings. It also should be used as part of a complete treatment program that includes counseling and psychosocial support.
The FDA is also requiring the manufacturer to conduct postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once monthly, and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first 2 months of treatment.
At recent joint meetings of the FDA’s Psychopharmacologic Drugs and Drug Safety and Risk Management advisory committees, panelists voted on Oct. 31 to recommend approval of Sublocade and on Nov. 1 for another subcutaneous buprenorphine injection formulation. These actions have not gone unnoticed by the American Medical Association.
“The AMA enthusiastically supports Food and Drug Administration Commissioner Scott Gottlieb’s efforts to advance policies and actions to treat those suffering from an opioid use disorder,” Patrice Harris, MD, immediate past chair of the American Medical Association Board of Trustees and a member of the AMA Opioid Task Force, said in a statement. “We also second his bold acknowledgment that criminal justice systems should offer [medication-assisted treatment] to those being detained. As he points out, ‘At the very moment when the criminal justice system could be dramatically lowering the risk of overdose, it is creating the conditions of reduced tolerance to opioids that substantially raises the risk of death upon release.’ With his clear explanation of the problem and solution, this situation can be remedied.”
The Food and Drug Administration has approved an extended-release, subcutaneous injection formulation of buprenorphine for use in treating moderate to severe opioid use disorder (OUD), the manufacturer of the drug announced Nov. 30.
The new product, called Sublocade, is a monthly injection intended for use in patients who have already begun treatment of OUD with transmucosal buprenorphine products, followed by a dose adjustment for a minimum of 7 days. Sublocade contains the partial mu-opioid agonist buprenorphine. By administering a consistent level of buprenorphine into the body, it ensures that levels of buprenorphine are delivered to the mu-opioid receptors, diminishing the effects of opioids, including the euphoric sensations associated with opioid use. During the clinical trial program, buprenorphine plasma concentrations of 2-3 ng/mL were found to bind to greater than 70% of mu-opioid receptors.
According to a statement from the FDA, Sublocade will be distributed only to health care providers as part of a Risk Evaluation and Mitigation Strategy to ensure that the product is not distributed directly to patients. Sublocade should be administered only by a health care professional. Self-injection of Sublocade into the blood stream instead of subcutaneously could lead to occlusion of blood vessels and embolism, according to one of the drug’s boxed warnings. It also should be used as part of a complete treatment program that includes counseling and psychosocial support.
The FDA is also requiring the manufacturer to conduct postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once monthly, and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first 2 months of treatment.
At recent joint meetings of the FDA’s Psychopharmacologic Drugs and Drug Safety and Risk Management advisory committees, panelists voted on Oct. 31 to recommend approval of Sublocade and on Nov. 1 for another subcutaneous buprenorphine injection formulation. These actions have not gone unnoticed by the American Medical Association.
“The AMA enthusiastically supports Food and Drug Administration Commissioner Scott Gottlieb’s efforts to advance policies and actions to treat those suffering from an opioid use disorder,” Patrice Harris, MD, immediate past chair of the American Medical Association Board of Trustees and a member of the AMA Opioid Task Force, said in a statement. “We also second his bold acknowledgment that criminal justice systems should offer [medication-assisted treatment] to those being detained. As he points out, ‘At the very moment when the criminal justice system could be dramatically lowering the risk of overdose, it is creating the conditions of reduced tolerance to opioids that substantially raises the risk of death upon release.’ With his clear explanation of the problem and solution, this situation can be remedied.”
Refractory FGFR-altered cholangiocarcinoma responds to FGFR kinase inhibitor
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: of 61 patients with chemotherapy refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
Major finding: BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions.
Data source: A phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
Disclosures: The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
FDA approves IL-17A antagonist for treating psoriatic arthritis
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
The interleukin-17A antagonist ixekizumab has been approved by the Food and Drug Administration for treating adults with active psoriatic arthritis (PsA), based on two phase 3 studies, the manufacturer announced in a written statement Dec. 1.
The Eli Lilly statement noted that the approval is based on two randomized, double-blind, placebo-controlled studies; one compared ixekizumab to placebo in patients with active PsA never treated with a biologic (SPIRIT-P1) and another tested the drug in those who had been treated with a tumor necrosis factor inhibitor (TNFi) previously (SPIRIT-P2).
Ixekizumab, marketed as Taltz by Eli Lilly, was first approved by the FDA in 2016 for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The statement did not provide information on dermatologic endpoints, but treatment with ixekizumab “resulted in an improvement in psoriatic skin lesions in patients with PsA,” as well as “in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis,” according to the prescribing information.
The recommended dose for patients with psoriatic arthritis is 160 mg by subcutaneous injection (two 80 mg injections) at baseline, followed by 80 mg every 4 weeks. When patients with psoriatic arthritis also have moderate-to-severe plaque psoriasis, then the prescribing information recommends following the dosing for psoriasis, which is 160 mg (two 80 mg injections) at baseline, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
The most common adverse reactions associated with ixekizumab are injection site reactions, upper respiratory tract infections, nausea, and tinea infections, according to the warnings and precautions section of the drug’s prescribing information, which lists the potential for serious infections, tuberculosis, and serious allergic reactions. Prescriptions come with a Medication Guide for patients.
Ensuring a smooth data collection process
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
Piloting of data collection is finally underway! My mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, and I are currently collaborating with the Surgical Intensive Care Unit at UC San Diego to conduct a daily review of urinary catheter (UC) necessity for patients on the unit, and subsequently coordinating with nursing staff on the unit to look for opportunities to implement UC alternatives.
As far as timeline, we are past the halfway point. One thing that has surprised me is how long it has taken to get piloting phase underway. To that end, I think that our initial project timeline was ambitious, especially because we were unclear on how well initial project enthusiasm would translate into subsequent project participation. Up until this point, our research approach has largely been to fine tune each process prospectively. For instance, we decided a pilot run of data collection prior to final project data collection would allow us to ensure a smoother data collection process. While this has slowed things initially, we are optimistic that this will allow us to progress more quickly and smoothly in the latter stages of the project. We are not currently planning to change this research approach for the time being, but we are open to the idea depending on how well the data piloting phase progresses.
Outside of data collection, the project has provided an excellent opportunity to learn and improve clinical skills. Specifically, the project has improved my understanding of the indications for urinary catheter use, as well as helped me to develop a more critical mindset regarding medical indications in general. The project has made me more aware of the importance of really asking and thinking about why a patient is on a specific medication or using a specific medical device, which is something that is very helpful for anticipating and avoiding errors in the clinical setting.
Overall, I have enjoyed my participation in the project to date and it has increased my enthusiasm for participating in a quality improvement project.
Victor Ekuta is a third-year medical student at UC San Diego.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
Piloting of data collection is finally underway! My mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, and I are currently collaborating with the Surgical Intensive Care Unit at UC San Diego to conduct a daily review of urinary catheter (UC) necessity for patients on the unit, and subsequently coordinating with nursing staff on the unit to look for opportunities to implement UC alternatives.
As far as timeline, we are past the halfway point. One thing that has surprised me is how long it has taken to get piloting phase underway. To that end, I think that our initial project timeline was ambitious, especially because we were unclear on how well initial project enthusiasm would translate into subsequent project participation. Up until this point, our research approach has largely been to fine tune each process prospectively. For instance, we decided a pilot run of data collection prior to final project data collection would allow us to ensure a smoother data collection process. While this has slowed things initially, we are optimistic that this will allow us to progress more quickly and smoothly in the latter stages of the project. We are not currently planning to change this research approach for the time being, but we are open to the idea depending on how well the data piloting phase progresses.
Outside of data collection, the project has provided an excellent opportunity to learn and improve clinical skills. Specifically, the project has improved my understanding of the indications for urinary catheter use, as well as helped me to develop a more critical mindset regarding medical indications in general. The project has made me more aware of the importance of really asking and thinking about why a patient is on a specific medication or using a specific medical device, which is something that is very helpful for anticipating and avoiding errors in the clinical setting.
Overall, I have enjoyed my participation in the project to date and it has increased my enthusiasm for participating in a quality improvement project.
Victor Ekuta is a third-year medical student at UC San Diego.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
Piloting of data collection is finally underway! My mentor, Dr. Ian Jenkins, an attending in the Division of Hospital Medicine at the University of California, San Diego, and I are currently collaborating with the Surgical Intensive Care Unit at UC San Diego to conduct a daily review of urinary catheter (UC) necessity for patients on the unit, and subsequently coordinating with nursing staff on the unit to look for opportunities to implement UC alternatives.
As far as timeline, we are past the halfway point. One thing that has surprised me is how long it has taken to get piloting phase underway. To that end, I think that our initial project timeline was ambitious, especially because we were unclear on how well initial project enthusiasm would translate into subsequent project participation. Up until this point, our research approach has largely been to fine tune each process prospectively. For instance, we decided a pilot run of data collection prior to final project data collection would allow us to ensure a smoother data collection process. While this has slowed things initially, we are optimistic that this will allow us to progress more quickly and smoothly in the latter stages of the project. We are not currently planning to change this research approach for the time being, but we are open to the idea depending on how well the data piloting phase progresses.
Outside of data collection, the project has provided an excellent opportunity to learn and improve clinical skills. Specifically, the project has improved my understanding of the indications for urinary catheter use, as well as helped me to develop a more critical mindset regarding medical indications in general. The project has made me more aware of the importance of really asking and thinking about why a patient is on a specific medication or using a specific medical device, which is something that is very helpful for anticipating and avoiding errors in the clinical setting.
Overall, I have enjoyed my participation in the project to date and it has increased my enthusiasm for participating in a quality improvement project.
Victor Ekuta is a third-year medical student at UC San Diego.
Drug receives fast track designation for FLT3+ rel/ref AML
The US Food and Drug Administration (FDA) has granted fast track designation to crenolanib for the treatment of patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia (AML).
Crenolanib is a benzimidazole type I tyrosine kinase inhibitor (TKI) that selectively inhibits signaling of wild-type and mutant isoforms of FLT3 and PDGFRα/β.
Crenolanib is being developed by Arog Pharmaceuticals, Inc.
The company is preparing for a phase 3, randomized, double-blind trial of crenolanib versus placebo in combination with best supportive care in patients with FLT3+ relapsed or refractory AML.
Results from a phase 2 trial of crenolanib in relapsed/refractory FLT3+ AML were presented at the 2016 ASCO Annual Meeting (abstract 7008).
The trial enrolled 69 patients who had a median age of 60 (range, 21-87). Twenty-nine patients had FLT3 ITD, 29 had ITD and D835, and 11 had D835.
Nineteen patients were TKI-naïve, 39 had received a prior TKI, and 11 had secondary AML.
Patients received crenolanib at 100 mg three times a day (n=43) or 66 mg/m2 three times a day (n=26).
In the TKI-naïve patients, the overall response rate (ORR) was 47% (n=9), and 37% of patients had a complete response (CR) or CR with incomplete count recovery (CRi). The median overall survival (OS) was 238 days (range, 25-547).
In patients who previously received a TKI, the ORR was 28% (n=11), and the CR/CRi rate was 15% (n=6). The median OS was 94 days (range, 8-338).
In patients with secondary AML, the ORR was 9% (n=1, partial response). The median OS in this group was 64 days (range, 27-221).
Treatment-emergent adverse events (all grades and grade 3/4, respectively) included nausea (70%, 9%), vomiting (58%, 9%), diarrhea (56%, 2%), fatigue (36%, 11%), febrile neutropenia (35%, 35%), pneumonia (32%, 23%), peripheral edema (30%, 2%), pleural effusion (21%, 8%), dyspnea (20%, 5%), and epistaxis (20%, 8%).
Two patients discontinued crenolanib due to adverse events. One patient discontinued due to grade 3 fatigue, abdominal pain, and headache. The other discontinued due to grade 3 pneumonia.
There were 2 neutropenic septic deaths, which occurred 2 days and 21 days after the discontinuation of crenolanib.
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA. 
The US Food and Drug Administration (FDA) has granted fast track designation to crenolanib for the treatment of patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia (AML).
Crenolanib is a benzimidazole type I tyrosine kinase inhibitor (TKI) that selectively inhibits signaling of wild-type and mutant isoforms of FLT3 and PDGFRα/β.
Crenolanib is being developed by Arog Pharmaceuticals, Inc.
The company is preparing for a phase 3, randomized, double-blind trial of crenolanib versus placebo in combination with best supportive care in patients with FLT3+ relapsed or refractory AML.
Results from a phase 2 trial of crenolanib in relapsed/refractory FLT3+ AML were presented at the 2016 ASCO Annual Meeting (abstract 7008).
The trial enrolled 69 patients who had a median age of 60 (range, 21-87). Twenty-nine patients had FLT3 ITD, 29 had ITD and D835, and 11 had D835.
Nineteen patients were TKI-naïve, 39 had received a prior TKI, and 11 had secondary AML.
Patients received crenolanib at 100 mg three times a day (n=43) or 66 mg/m2 three times a day (n=26).
In the TKI-naïve patients, the overall response rate (ORR) was 47% (n=9), and 37% of patients had a complete response (CR) or CR with incomplete count recovery (CRi). The median overall survival (OS) was 238 days (range, 25-547).
In patients who previously received a TKI, the ORR was 28% (n=11), and the CR/CRi rate was 15% (n=6). The median OS was 94 days (range, 8-338).
In patients with secondary AML, the ORR was 9% (n=1, partial response). The median OS in this group was 64 days (range, 27-221).
Treatment-emergent adverse events (all grades and grade 3/4, respectively) included nausea (70%, 9%), vomiting (58%, 9%), diarrhea (56%, 2%), fatigue (36%, 11%), febrile neutropenia (35%, 35%), pneumonia (32%, 23%), peripheral edema (30%, 2%), pleural effusion (21%, 8%), dyspnea (20%, 5%), and epistaxis (20%, 8%).
Two patients discontinued crenolanib due to adverse events. One patient discontinued due to grade 3 fatigue, abdominal pain, and headache. The other discontinued due to grade 3 pneumonia.
There were 2 neutropenic septic deaths, which occurred 2 days and 21 days after the discontinuation of crenolanib.
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
The US Food and Drug Administration (FDA) has granted fast track designation to crenolanib for the treatment of patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia (AML).
Crenolanib is a benzimidazole type I tyrosine kinase inhibitor (TKI) that selectively inhibits signaling of wild-type and mutant isoforms of FLT3 and PDGFRα/β.
Crenolanib is being developed by Arog Pharmaceuticals, Inc.
The company is preparing for a phase 3, randomized, double-blind trial of crenolanib versus placebo in combination with best supportive care in patients with FLT3+ relapsed or refractory AML.
Results from a phase 2 trial of crenolanib in relapsed/refractory FLT3+ AML were presented at the 2016 ASCO Annual Meeting (abstract 7008).
The trial enrolled 69 patients who had a median age of 60 (range, 21-87). Twenty-nine patients had FLT3 ITD, 29 had ITD and D835, and 11 had D835.
Nineteen patients were TKI-naïve, 39 had received a prior TKI, and 11 had secondary AML.
Patients received crenolanib at 100 mg three times a day (n=43) or 66 mg/m2 three times a day (n=26).
In the TKI-naïve patients, the overall response rate (ORR) was 47% (n=9), and 37% of patients had a complete response (CR) or CR with incomplete count recovery (CRi). The median overall survival (OS) was 238 days (range, 25-547).
In patients who previously received a TKI, the ORR was 28% (n=11), and the CR/CRi rate was 15% (n=6). The median OS was 94 days (range, 8-338).
In patients with secondary AML, the ORR was 9% (n=1, partial response). The median OS in this group was 64 days (range, 27-221).
Treatment-emergent adverse events (all grades and grade 3/4, respectively) included nausea (70%, 9%), vomiting (58%, 9%), diarrhea (56%, 2%), fatigue (36%, 11%), febrile neutropenia (35%, 35%), pneumonia (32%, 23%), peripheral edema (30%, 2%), pleural effusion (21%, 8%), dyspnea (20%, 5%), and epistaxis (20%, 8%).
Two patients discontinued crenolanib due to adverse events. One patient discontinued due to grade 3 fatigue, abdominal pain, and headache. The other discontinued due to grade 3 pneumonia.
There were 2 neutropenic septic deaths, which occurred 2 days and 21 days after the discontinuation of crenolanib.
About fast track designation
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
E-visits less likely to generate antibiotic prescriptions for common ailments
MONTREAL – When the same patient was assessed in person and via an electronic visit (e-visit) for several common complaints, a prescription for antibiotics was more likely to be generated from the face-to-face encounter.
In a recent study, if antibiotics were prescribed in one setting, but not the other, the office visit rather than the e-visit was where the antibiotic prescription was written in 73% of cases. Visits for sinus problems and vaginal symptoms made up over 80% of these cases of nonconcordant prescribing.
The study compared the diagnosis and treatment of five common acute conditions in an outpatient and e-visit setting, examining the concordance of both diagnosis and treatment between the two settings for complaints of vaginal irritation or discharge, urinary symptoms, sinus problems, rash, and diarrhea.
Outcomes tracked included concordance between the office visits and mock e-visits for the diagnosis, whether antibiotics were prescribed, and the general choice of antibiotics. Determinations about concordance were made by a third provider who was not involved with either the in-person visit or the mock e-visit, said Dr. Player, of the department of family medicine at the Medical University of South Carolina, Charleston.
Nonconcordance in treatment could occur either because an antibiotic was prescribed in one setting, but not the other, or because the broad choice of antibiotic class differed between the two settings.
Adult patients who came to the outpatient clinic and agreed to be enrolled in the study also completed the e-visit questionnaires appropriate to their condition before they saw the provider in an office visit. Thus, mock e-visits were created that mirrored the office visit with the e-visit format used in practice.
At a later point in time, the blinded e-visit questionnaires were given to e-visit providers who treated the patients as they would if the questionnaires had been generated in an actual e-visit.
The study generated a total of 142 office visits with accompanying mock e-visits, but 29 were excluded for lack of completeness or inappropriateness for e-visit care. In all, 113 paired visits were evaluated. All but seven patients (94%) were female; slightly more than half (53%) of patients were aged 45 years or older.
About one-third of visits (34%; n = 38) were for vaginal discharge or irritation. Sinus problems were reported by 36 patients (32%). Twenty-five patients (22%) reported urinary problems, while eight patients (7%) reported diarrhea. Six patients (5%) complained of a rash.
In total, 78 visit pairs (69%) were assessed as being concordant. Of the 35 nonconcordant visits, over half (54%) were for sinus problems, 40% were for vaginal discharge or irritation, and 6% were for rash. None of the visits involving urinary problems or diarrhea were assessed as nonconcordant.
Examining the data another way, Dr. Player and his coinvestigators also looked at how many visits involved antibiotic prescribing, and how many of those visits were assessed as nonconcordant. Of the 96 patients (85%) who were prescribed antibiotics, 37 had office and mock e-visits that were assessed as discordant in antibiotic prescribing.
Of these visit pairs, about half (51%) were for sinus problems, and a third (32%) were for vaginal complaints. Urinary complaints made up 11% of the nonconcordant visit pairs where antibiotics were prescribed, and rashes made up the remaining 5%.
Diagnostic concordance was seen in about two-thirds of rash (67%) and vaginal discharge (63%) visit pairs. Concordance of diagnosis for sinus problems occurred in fewer than half (47%) of visit pairs.
Dr. Player said that the investigators excluded visits involving urinary or vaginal complaints that did not have an accompanying urinalysis or vaginal wet mount. This decision was made because the standard of care for both office visits and e-visits requires these laboratory tests for diagnosis, he said.
The study design came with some limitations, said Dr. Player. “Patients self-select for e-visits, and the patients in this study might be different from those in true e-visit encounters,” he said. Also, the diagnosis and treatment of sinus problems, rash, and diarrhea relied on clinical judgment alone in each visit setting. Still, he said, the study supports what many clinicians report anecdotally: Patients want to leave the office knowing that the clinician has “done something” for them, and often, that means walking out with a prescription in hand.
Dr. Player reported no conflicts of interest.
[email protected]
On Twitter @karioakes
MONTREAL – When the same patient was assessed in person and via an electronic visit (e-visit) for several common complaints, a prescription for antibiotics was more likely to be generated from the face-to-face encounter.
In a recent study, if antibiotics were prescribed in one setting, but not the other, the office visit rather than the e-visit was where the antibiotic prescription was written in 73% of cases. Visits for sinus problems and vaginal symptoms made up over 80% of these cases of nonconcordant prescribing.
The study compared the diagnosis and treatment of five common acute conditions in an outpatient and e-visit setting, examining the concordance of both diagnosis and treatment between the two settings for complaints of vaginal irritation or discharge, urinary symptoms, sinus problems, rash, and diarrhea.
Outcomes tracked included concordance between the office visits and mock e-visits for the diagnosis, whether antibiotics were prescribed, and the general choice of antibiotics. Determinations about concordance were made by a third provider who was not involved with either the in-person visit or the mock e-visit, said Dr. Player, of the department of family medicine at the Medical University of South Carolina, Charleston.
Nonconcordance in treatment could occur either because an antibiotic was prescribed in one setting, but not the other, or because the broad choice of antibiotic class differed between the two settings.
Adult patients who came to the outpatient clinic and agreed to be enrolled in the study also completed the e-visit questionnaires appropriate to their condition before they saw the provider in an office visit. Thus, mock e-visits were created that mirrored the office visit with the e-visit format used in practice.
At a later point in time, the blinded e-visit questionnaires were given to e-visit providers who treated the patients as they would if the questionnaires had been generated in an actual e-visit.
The study generated a total of 142 office visits with accompanying mock e-visits, but 29 were excluded for lack of completeness or inappropriateness for e-visit care. In all, 113 paired visits were evaluated. All but seven patients (94%) were female; slightly more than half (53%) of patients were aged 45 years or older.
About one-third of visits (34%; n = 38) were for vaginal discharge or irritation. Sinus problems were reported by 36 patients (32%). Twenty-five patients (22%) reported urinary problems, while eight patients (7%) reported diarrhea. Six patients (5%) complained of a rash.
In total, 78 visit pairs (69%) were assessed as being concordant. Of the 35 nonconcordant visits, over half (54%) were for sinus problems, 40% were for vaginal discharge or irritation, and 6% were for rash. None of the visits involving urinary problems or diarrhea were assessed as nonconcordant.
Examining the data another way, Dr. Player and his coinvestigators also looked at how many visits involved antibiotic prescribing, and how many of those visits were assessed as nonconcordant. Of the 96 patients (85%) who were prescribed antibiotics, 37 had office and mock e-visits that were assessed as discordant in antibiotic prescribing.
Of these visit pairs, about half (51%) were for sinus problems, and a third (32%) were for vaginal complaints. Urinary complaints made up 11% of the nonconcordant visit pairs where antibiotics were prescribed, and rashes made up the remaining 5%.
Diagnostic concordance was seen in about two-thirds of rash (67%) and vaginal discharge (63%) visit pairs. Concordance of diagnosis for sinus problems occurred in fewer than half (47%) of visit pairs.
Dr. Player said that the investigators excluded visits involving urinary or vaginal complaints that did not have an accompanying urinalysis or vaginal wet mount. This decision was made because the standard of care for both office visits and e-visits requires these laboratory tests for diagnosis, he said.
The study design came with some limitations, said Dr. Player. “Patients self-select for e-visits, and the patients in this study might be different from those in true e-visit encounters,” he said. Also, the diagnosis and treatment of sinus problems, rash, and diarrhea relied on clinical judgment alone in each visit setting. Still, he said, the study supports what many clinicians report anecdotally: Patients want to leave the office knowing that the clinician has “done something” for them, and often, that means walking out with a prescription in hand.
Dr. Player reported no conflicts of interest.
[email protected]
On Twitter @karioakes
MONTREAL – When the same patient was assessed in person and via an electronic visit (e-visit) for several common complaints, a prescription for antibiotics was more likely to be generated from the face-to-face encounter.
In a recent study, if antibiotics were prescribed in one setting, but not the other, the office visit rather than the e-visit was where the antibiotic prescription was written in 73% of cases. Visits for sinus problems and vaginal symptoms made up over 80% of these cases of nonconcordant prescribing.
The study compared the diagnosis and treatment of five common acute conditions in an outpatient and e-visit setting, examining the concordance of both diagnosis and treatment between the two settings for complaints of vaginal irritation or discharge, urinary symptoms, sinus problems, rash, and diarrhea.
Outcomes tracked included concordance between the office visits and mock e-visits for the diagnosis, whether antibiotics were prescribed, and the general choice of antibiotics. Determinations about concordance were made by a third provider who was not involved with either the in-person visit or the mock e-visit, said Dr. Player, of the department of family medicine at the Medical University of South Carolina, Charleston.
Nonconcordance in treatment could occur either because an antibiotic was prescribed in one setting, but not the other, or because the broad choice of antibiotic class differed between the two settings.
Adult patients who came to the outpatient clinic and agreed to be enrolled in the study also completed the e-visit questionnaires appropriate to their condition before they saw the provider in an office visit. Thus, mock e-visits were created that mirrored the office visit with the e-visit format used in practice.
At a later point in time, the blinded e-visit questionnaires were given to e-visit providers who treated the patients as they would if the questionnaires had been generated in an actual e-visit.
The study generated a total of 142 office visits with accompanying mock e-visits, but 29 were excluded for lack of completeness or inappropriateness for e-visit care. In all, 113 paired visits were evaluated. All but seven patients (94%) were female; slightly more than half (53%) of patients were aged 45 years or older.
About one-third of visits (34%; n = 38) were for vaginal discharge or irritation. Sinus problems were reported by 36 patients (32%). Twenty-five patients (22%) reported urinary problems, while eight patients (7%) reported diarrhea. Six patients (5%) complained of a rash.
In total, 78 visit pairs (69%) were assessed as being concordant. Of the 35 nonconcordant visits, over half (54%) were for sinus problems, 40% were for vaginal discharge or irritation, and 6% were for rash. None of the visits involving urinary problems or diarrhea were assessed as nonconcordant.
Examining the data another way, Dr. Player and his coinvestigators also looked at how many visits involved antibiotic prescribing, and how many of those visits were assessed as nonconcordant. Of the 96 patients (85%) who were prescribed antibiotics, 37 had office and mock e-visits that were assessed as discordant in antibiotic prescribing.
Of these visit pairs, about half (51%) were for sinus problems, and a third (32%) were for vaginal complaints. Urinary complaints made up 11% of the nonconcordant visit pairs where antibiotics were prescribed, and rashes made up the remaining 5%.
Diagnostic concordance was seen in about two-thirds of rash (67%) and vaginal discharge (63%) visit pairs. Concordance of diagnosis for sinus problems occurred in fewer than half (47%) of visit pairs.
Dr. Player said that the investigators excluded visits involving urinary or vaginal complaints that did not have an accompanying urinalysis or vaginal wet mount. This decision was made because the standard of care for both office visits and e-visits requires these laboratory tests for diagnosis, he said.
The study design came with some limitations, said Dr. Player. “Patients self-select for e-visits, and the patients in this study might be different from those in true e-visit encounters,” he said. Also, the diagnosis and treatment of sinus problems, rash, and diarrhea relied on clinical judgment alone in each visit setting. Still, he said, the study supports what many clinicians report anecdotally: Patients want to leave the office knowing that the clinician has “done something” for them, and often, that means walking out with a prescription in hand.
Dr. Player reported no conflicts of interest.
[email protected]
On Twitter @karioakes
AT NAPCRG 2017
Key clinical point:
Major finding: Antibiotics were given in the office but not the e-visit in 73% of cases.
Data source: Prospective study of 113 office visits that were paired with independently assessed e-visits for the same patient and complaint.
Disclosures: Dr. Player reported no conflicts of interest.
How to assess a patient for a bisphosphonate drug holiday
Recorded at the 2017 meeting of the North American Menopause Society
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Recorded at the 2017 meeting of the North American Menopause Society
Recorded at the 2017 meeting of the North American Menopause Society
