Susan London

CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.

One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.

However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.

Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.

“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.

Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”

“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”

A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.

Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”

“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”

Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.

With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).

“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.

Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.

In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.

Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”

Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.

An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.

“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.

Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.

CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.

One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.

However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.

Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.

“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.

Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”

“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”

A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.

Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”

“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”

Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.

With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).

“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.

Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.

In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.

Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”

Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.

An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.

“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.

Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.

CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.

One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.

However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.

Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.

“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.

Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”

“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”

A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.

Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”

“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”

Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.

With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).

“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.

Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.

In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.

Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”

Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.

An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.

“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.

Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.

CHICAGO  – A drug that targets cyclin-dependent kinases (CDKs) may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy, suggests the randomized PALOMA-3 trial (PALbociclib: Ongoing trials in the Management of breast cAncer).

In the phase III trial, palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—prolonged median progression-free survival by about 5 months compared with placebo when added to standard endocrine therapy, according to interim data reported at the annual meeting of the American Society of Clinical Oncology. These efficacy findings led to early stopping of the trial.

“This study confirms that as breast cancers become resistant to endocrine therapy, CDK 4/6 is still a target and palbociclib is still very active,” lead study author Dr. Nicholas C. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, said in a press briefing.

Earlier this year, the Food and Drug Administration approved palbociclib in combination with letrozole as first-line therapy for estrogen receptor–positive, HER2-negative metastatic breast cancer in postmenopausal women. But that is a different patient population, still having endocrine-sensitive disease, he noted.

The investigators opted to study palbociclib in combination with a different hormonal therapy, fulvestrant, in the trial for several reasons. “Fulvestrant is likely the most active hormone therapy when the first hormone therapy has stopped working,” Dr. Turner explained. Additionally, “there is quite significant data looking at cell line models that you get synergy between the two [drugs] in models of endocrine resistance.”

“I think the PALOMA-3 trial results are incredibly important for women with hormone receptor–positive advanced or metastatic breast cancer, and it represents a new standard of care option after progression of disease on prior endocrine therapy,” commented Dr. Don S. Dizon, an ASCO spokesperson and moderator of the press briefing, as well as clinical co-director of Gynecologic Oncology at the Massachusetts General Hospital, Boston.

“For women with advanced breast cancer, it’s remarkable to be able to stall disease progression and stave off the need for chemotherapy for months with a simple pill. In one of the most common forms of advanced breast cancer, palbociclib works in both older and younger women,” he said.

The 521 women in the Pfizer-funded trial had hormone receptor–positive, HER2-negative metastatic breast cancer and had experienced a failure of prior endocrine therapy. They were randomized in 2:1 ratio to palbociclib (Ibrance) or placebo, each in addition to fulvestrant (Faslodex). Of note, 21% were premenopausal, and this group additionally received goserelin (Zoladex).
Results of the preplanned interim analysis showed that median progression-free survival, the trial’s primary endpoint, was 9.2 months with palbociclib versus 3.8 months with placebo (hazard ratio, 0.42; P less than .000001). “The curves separate early and then continue to separate with ongoing follow-up,” Dr. Turner noted.

“Benefit from palbociclib was demonstrated across all prespecified subgroups, including in both pre- and post-menopausal women,” he further reported. Overall survival results are not yet mature, and quality of life data will be reported separately.

Combination therapy was generally well tolerated, Dr. Turner said.
The most common any-grade adverse events seen with the drug versus placebo were hematologic, with sharply higher rates of neutropenia (79% vs. 3%) and leukopenia (46% vs 4%); however, the rate of febrile neutropenia was low and identical, at 0.6% in each group. Additionally, only 2.6% of patients in the palbociclib group had to stop treatment because of adverse events.

The efficacy of the initial palbociclib-letrozole combination is being further assessed in the ongoing PALOMA-2 trial, according to Dr. Turner. In addition, the investigators may evaluate palbociclib-containing combinations in early-stage breast cancer.

CHICAGO  – A drug that targets cyclin-dependent kinases (CDKs) may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy, suggests the randomized PALOMA-3 trial (PALbociclib: Ongoing trials in the Management of breast cAncer).

In the phase III trial, palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—prolonged median progression-free survival by about 5 months compared with placebo when added to standard endocrine therapy, according to interim data reported at the annual meeting of the American Society of Clinical Oncology. These efficacy findings led to early stopping of the trial.

“This study confirms that as breast cancers become resistant to endocrine therapy, CDK 4/6 is still a target and palbociclib is still very active,” lead study author Dr. Nicholas C. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, said in a press briefing.

Earlier this year, the Food and Drug Administration approved palbociclib in combination with letrozole as first-line therapy for estrogen receptor–positive, HER2-negative metastatic breast cancer in postmenopausal women. But that is a different patient population, still having endocrine-sensitive disease, he noted.

The investigators opted to study palbociclib in combination with a different hormonal therapy, fulvestrant, in the trial for several reasons. “Fulvestrant is likely the most active hormone therapy when the first hormone therapy has stopped working,” Dr. Turner explained. Additionally, “there is quite significant data looking at cell line models that you get synergy between the two [drugs] in models of endocrine resistance.”

“I think the PALOMA-3 trial results are incredibly important for women with hormone receptor–positive advanced or metastatic breast cancer, and it represents a new standard of care option after progression of disease on prior endocrine therapy,” commented Dr. Don S. Dizon, an ASCO spokesperson and moderator of the press briefing, as well as clinical co-director of Gynecologic Oncology at the Massachusetts General Hospital, Boston.

“For women with advanced breast cancer, it’s remarkable to be able to stall disease progression and stave off the need for chemotherapy for months with a simple pill. In one of the most common forms of advanced breast cancer, palbociclib works in both older and younger women,” he said.

The 521 women in the Pfizer-funded trial had hormone receptor–positive, HER2-negative metastatic breast cancer and had experienced a failure of prior endocrine therapy. They were randomized in 2:1 ratio to palbociclib (Ibrance) or placebo, each in addition to fulvestrant (Faslodex). Of note, 21% were premenopausal, and this group additionally received goserelin (Zoladex).
Results of the preplanned interim analysis showed that median progression-free survival, the trial’s primary endpoint, was 9.2 months with palbociclib versus 3.8 months with placebo (hazard ratio, 0.42; P less than .000001). “The curves separate early and then continue to separate with ongoing follow-up,” Dr. Turner noted.

“Benefit from palbociclib was demonstrated across all prespecified subgroups, including in both pre- and post-menopausal women,” he further reported. Overall survival results are not yet mature, and quality of life data will be reported separately.

Combination therapy was generally well tolerated, Dr. Turner said.
The most common any-grade adverse events seen with the drug versus placebo were hematologic, with sharply higher rates of neutropenia (79% vs. 3%) and leukopenia (46% vs 4%); however, the rate of febrile neutropenia was low and identical, at 0.6% in each group. Additionally, only 2.6% of patients in the palbociclib group had to stop treatment because of adverse events.

The efficacy of the initial palbociclib-letrozole combination is being further assessed in the ongoing PALOMA-2 trial, according to Dr. Turner. In addition, the investigators may evaluate palbociclib-containing combinations in early-stage breast cancer.

CHICAGO  – A drug that targets cyclin-dependent kinases (CDKs) may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy, suggests the randomized PALOMA-3 trial (PALbociclib: Ongoing trials in the Management of breast cAncer).

In the phase III trial, palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—prolonged median progression-free survival by about 5 months compared with placebo when added to standard endocrine therapy, according to interim data reported at the annual meeting of the American Society of Clinical Oncology. These efficacy findings led to early stopping of the trial.

“This study confirms that as breast cancers become resistant to endocrine therapy, CDK 4/6 is still a target and palbociclib is still very active,” lead study author Dr. Nicholas C. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, said in a press briefing.

Earlier this year, the Food and Drug Administration approved palbociclib in combination with letrozole as first-line therapy for estrogen receptor–positive, HER2-negative metastatic breast cancer in postmenopausal women. But that is a different patient population, still having endocrine-sensitive disease, he noted.

The investigators opted to study palbociclib in combination with a different hormonal therapy, fulvestrant, in the trial for several reasons. “Fulvestrant is likely the most active hormone therapy when the first hormone therapy has stopped working,” Dr. Turner explained. Additionally, “there is quite significant data looking at cell line models that you get synergy between the two [drugs] in models of endocrine resistance.”

“I think the PALOMA-3 trial results are incredibly important for women with hormone receptor–positive advanced or metastatic breast cancer, and it represents a new standard of care option after progression of disease on prior endocrine therapy,” commented Dr. Don S. Dizon, an ASCO spokesperson and moderator of the press briefing, as well as clinical co-director of Gynecologic Oncology at the Massachusetts General Hospital, Boston.

“For women with advanced breast cancer, it’s remarkable to be able to stall disease progression and stave off the need for chemotherapy for months with a simple pill. In one of the most common forms of advanced breast cancer, palbociclib works in both older and younger women,” he said.

The 521 women in the Pfizer-funded trial had hormone receptor–positive, HER2-negative metastatic breast cancer and had experienced a failure of prior endocrine therapy. They were randomized in 2:1 ratio to palbociclib (Ibrance) or placebo, each in addition to fulvestrant (Faslodex). Of note, 21% were premenopausal, and this group additionally received goserelin (Zoladex).
Results of the preplanned interim analysis showed that median progression-free survival, the trial’s primary endpoint, was 9.2 months with palbociclib versus 3.8 months with placebo (hazard ratio, 0.42; P less than .000001). “The curves separate early and then continue to separate with ongoing follow-up,” Dr. Turner noted.

“Benefit from palbociclib was demonstrated across all prespecified subgroups, including in both pre- and post-menopausal women,” he further reported. Overall survival results are not yet mature, and quality of life data will be reported separately.

Combination therapy was generally well tolerated, Dr. Turner said.
The most common any-grade adverse events seen with the drug versus placebo were hematologic, with sharply higher rates of neutropenia (79% vs. 3%) and leukopenia (46% vs 4%); however, the rate of febrile neutropenia was low and identical, at 0.6% in each group. Additionally, only 2.6% of patients in the palbociclib group had to stop treatment because of adverse events.

The efficacy of the initial palbociclib-letrozole combination is being further assessed in the ongoing PALOMA-2 trial, according to Dr. Turner. In addition, the investigators may evaluate palbociclib-containing combinations in early-stage breast cancer.

CHICAGO – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.

Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.

CHICAGO – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.

Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.

CHICAGO – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.

Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.

“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”

“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”

Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).

Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.

In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.

The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.

Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).

“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.

With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.

As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.

Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.

CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.

“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”

“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”

Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).

Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.

In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.

The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.

Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).

“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.

With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.

As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.

Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.

CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.

“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”

“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”

Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).

Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.

In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.

The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.

Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).

“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.

With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.

As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.

Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

SEATTLE – A new study using an analytic framework grounded in behavior change theory shows several modifiable ways to help patients with knee and/or hip osteoarthritis to exercise, the most influential being beliefs about exercise, medical advice, gym referral, supervision, and encouragement, according to a report at the World Congress on Osteoarthritis.

“Our study provides a comprehensive synthesis of the many barriers and facilitators faced by those with osteoarthritis regarding intentional exercise,” commented lead investigator Philippa Nicolson, a research scientist at the Centre for Health, Exercise & Sports Medicine, University of Melbourne.

“Importantly, exercise adherence is not a problem that patients can solve on their own. Clinicians must take an active and leading role in identifying and considering barriers and facilitators to exercise, and engage with patients to create a patient-centered exercise plan that suits each individual’s needs and circumstances,” she recommended. “Clinicians must also help patients to gain the knowledge and skills that they need in order to adhere to exercise in the long term.”

In an interview, Stephen P. Messier, Ph.D., session comoderator and professor and director of both the J.B. Snow Biomechanics Laboratory and the Wake Forest University Runners’ Clinic in Winston-Salem, N. C., said, “A lot of this is not new information, I would say, but it really is important that [clinicians] understand that people who have been sedentary all their lives need help. They can’t do it on their own.”

Critical issues are how to stay in contact with patients and give them ongoing support in the long term, he noted, adding that, with social media and other methods, physicians can give patients personal help in the beginning and then wean them off of that help but still stay in contact in some way so patients feel like they have someone to talk to and someone that cares.

The physician plays a key role in the process, all the way from prescribing exercise to identifying suitable facilities to monitoring progress. “When your doctor cares about it, then older folks are going to do it because they really pay attention to what the physician says,” Dr. Messier said.

Introducing the study, Ms. Nicolson commented, “Exercise is a core component of osteoarthritis management and is now recommended in all clinical guidelines. High-quality evidence for the benefits of exercise in improving pain and function for those with lower-limb osteoarthritis are well established. However, exercise is globally underutilized, and among those for whom exercise is prescribed, adherence is found to be poor, particularly in the long term.”

“Understanding the barriers and facilitators to exercise will allow clinicians to change their practice to better facilitate adherence and allow researchers to develop and evaluate behavioral interventions targeting improved adherence,” she explained. “Given that initiating and adhering to exercise often requires significant behavior change, the use of behavior change theory is essential. In order to facilitate people with osteoarthritis to exercise, we need to analyze the behaviors influencing exercise participation. Interventions based on behavior change theory have been found to be significantly more successful than those that are not.”

The investigators conducted a scoping review to identify exercise barriers and facilitators in this population. They identified 23 relevant articles on intentional exercise (supervised or not and prescribed or self-initiated) among a total of 4,633 patients aged 45 years or older with hip and/or knee osteoarthritis.

Most of the more than 200 barriers and facilitators extracted from the articles were modifiable, according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The investigators mapped these modifiable factors onto domains of the Theoretical Domains Framework, which integrates multiple behavior change theories into a single framework and is aimed at helping researchers identify processes that do and do not work (Implement. Sci. 2012;7:37). They found that the barriers and facilitators mapped onto all 14 domains.

Among highlights, the many barriers mapping onto the framework’s Environmental Context and Resources domain included having to descend hills or stairs during a walking program, inability to find a suitable exercise, and rigidity of the program. Facilitators mapping onto this domain included use of a pedometer, physical therapist guidance, and receipt of a gym referral from the doctor.

Barriers mapping onto the Beliefs About Consequences domain included a belief that exercise has limited benefit, fear about damaging the joint further, and concern about precipitating pain.

Facilitators mapping onto the Reinforcement domain included medical advice to exercise, telephone reinforcement, and getting physician encouragement.

“Our findings have a number of clinical implications,” commented Ms. Nicolson.

“Given the many barriers that we identified linking to a person’s environment and resources, this highlights the need for individualized exercise tailored to each person’s situation,” she said. “Many barriers also relate to a person’s beliefs about their ability and consequences of exercise … This highlights the need for thorough and accurate education to each and every patient about their capabilities and the likely benefits of exercise.”

“Reinforcement, both internal and external, was frequently identified as a facilitator to exercise. The use of such things as logbooks, diaries, ongoing encouragement, and clinician advice to exercise can utilize these facilitators,” she concluded.

Ms. Nicolson disclosed no relevant conflicts of interest.

SEATTLE – A new study using an analytic framework grounded in behavior change theory shows several modifiable ways to help patients with knee and/or hip osteoarthritis to exercise, the most influential being beliefs about exercise, medical advice, gym referral, supervision, and encouragement, according to a report at the World Congress on Osteoarthritis.

“Our study provides a comprehensive synthesis of the many barriers and facilitators faced by those with osteoarthritis regarding intentional exercise,” commented lead investigator Philippa Nicolson, a research scientist at the Centre for Health, Exercise & Sports Medicine, University of Melbourne.

“Importantly, exercise adherence is not a problem that patients can solve on their own. Clinicians must take an active and leading role in identifying and considering barriers and facilitators to exercise, and engage with patients to create a patient-centered exercise plan that suits each individual’s needs and circumstances,” she recommended. “Clinicians must also help patients to gain the knowledge and skills that they need in order to adhere to exercise in the long term.”

In an interview, Stephen P. Messier, Ph.D., session comoderator and professor and director of both the J.B. Snow Biomechanics Laboratory and the Wake Forest University Runners’ Clinic in Winston-Salem, N. C., said, “A lot of this is not new information, I would say, but it really is important that [clinicians] understand that people who have been sedentary all their lives need help. They can’t do it on their own.”

Critical issues are how to stay in contact with patients and give them ongoing support in the long term, he noted, adding that, with social media and other methods, physicians can give patients personal help in the beginning and then wean them off of that help but still stay in contact in some way so patients feel like they have someone to talk to and someone that cares.

The physician plays a key role in the process, all the way from prescribing exercise to identifying suitable facilities to monitoring progress. “When your doctor cares about it, then older folks are going to do it because they really pay attention to what the physician says,” Dr. Messier said.

Introducing the study, Ms. Nicolson commented, “Exercise is a core component of osteoarthritis management and is now recommended in all clinical guidelines. High-quality evidence for the benefits of exercise in improving pain and function for those with lower-limb osteoarthritis are well established. However, exercise is globally underutilized, and among those for whom exercise is prescribed, adherence is found to be poor, particularly in the long term.”

“Understanding the barriers and facilitators to exercise will allow clinicians to change their practice to better facilitate adherence and allow researchers to develop and evaluate behavioral interventions targeting improved adherence,” she explained. “Given that initiating and adhering to exercise often requires significant behavior change, the use of behavior change theory is essential. In order to facilitate people with osteoarthritis to exercise, we need to analyze the behaviors influencing exercise participation. Interventions based on behavior change theory have been found to be significantly more successful than those that are not.”

The investigators conducted a scoping review to identify exercise barriers and facilitators in this population. They identified 23 relevant articles on intentional exercise (supervised or not and prescribed or self-initiated) among a total of 4,633 patients aged 45 years or older with hip and/or knee osteoarthritis.

Most of the more than 200 barriers and facilitators extracted from the articles were modifiable, according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The investigators mapped these modifiable factors onto domains of the Theoretical Domains Framework, which integrates multiple behavior change theories into a single framework and is aimed at helping researchers identify processes that do and do not work (Implement. Sci. 2012;7:37). They found that the barriers and facilitators mapped onto all 14 domains.

Among highlights, the many barriers mapping onto the framework’s Environmental Context and Resources domain included having to descend hills or stairs during a walking program, inability to find a suitable exercise, and rigidity of the program. Facilitators mapping onto this domain included use of a pedometer, physical therapist guidance, and receipt of a gym referral from the doctor.

Barriers mapping onto the Beliefs About Consequences domain included a belief that exercise has limited benefit, fear about damaging the joint further, and concern about precipitating pain.

Facilitators mapping onto the Reinforcement domain included medical advice to exercise, telephone reinforcement, and getting physician encouragement.

“Our findings have a number of clinical implications,” commented Ms. Nicolson.

“Given the many barriers that we identified linking to a person’s environment and resources, this highlights the need for individualized exercise tailored to each person’s situation,” she said. “Many barriers also relate to a person’s beliefs about their ability and consequences of exercise … This highlights the need for thorough and accurate education to each and every patient about their capabilities and the likely benefits of exercise.”

“Reinforcement, both internal and external, was frequently identified as a facilitator to exercise. The use of such things as logbooks, diaries, ongoing encouragement, and clinician advice to exercise can utilize these facilitators,” she concluded.

Ms. Nicolson disclosed no relevant conflicts of interest.

SEATTLE – A new study using an analytic framework grounded in behavior change theory shows several modifiable ways to help patients with knee and/or hip osteoarthritis to exercise, the most influential being beliefs about exercise, medical advice, gym referral, supervision, and encouragement, according to a report at the World Congress on Osteoarthritis.

“Our study provides a comprehensive synthesis of the many barriers and facilitators faced by those with osteoarthritis regarding intentional exercise,” commented lead investigator Philippa Nicolson, a research scientist at the Centre for Health, Exercise & Sports Medicine, University of Melbourne.

“Importantly, exercise adherence is not a problem that patients can solve on their own. Clinicians must take an active and leading role in identifying and considering barriers and facilitators to exercise, and engage with patients to create a patient-centered exercise plan that suits each individual’s needs and circumstances,” she recommended. “Clinicians must also help patients to gain the knowledge and skills that they need in order to adhere to exercise in the long term.”

In an interview, Stephen P. Messier, Ph.D., session comoderator and professor and director of both the J.B. Snow Biomechanics Laboratory and the Wake Forest University Runners’ Clinic in Winston-Salem, N. C., said, “A lot of this is not new information, I would say, but it really is important that [clinicians] understand that people who have been sedentary all their lives need help. They can’t do it on their own.”

Critical issues are how to stay in contact with patients and give them ongoing support in the long term, he noted, adding that, with social media and other methods, physicians can give patients personal help in the beginning and then wean them off of that help but still stay in contact in some way so patients feel like they have someone to talk to and someone that cares.

The physician plays a key role in the process, all the way from prescribing exercise to identifying suitable facilities to monitoring progress. “When your doctor cares about it, then older folks are going to do it because they really pay attention to what the physician says,” Dr. Messier said.

Introducing the study, Ms. Nicolson commented, “Exercise is a core component of osteoarthritis management and is now recommended in all clinical guidelines. High-quality evidence for the benefits of exercise in improving pain and function for those with lower-limb osteoarthritis are well established. However, exercise is globally underutilized, and among those for whom exercise is prescribed, adherence is found to be poor, particularly in the long term.”

“Understanding the barriers and facilitators to exercise will allow clinicians to change their practice to better facilitate adherence and allow researchers to develop and evaluate behavioral interventions targeting improved adherence,” she explained. “Given that initiating and adhering to exercise often requires significant behavior change, the use of behavior change theory is essential. In order to facilitate people with osteoarthritis to exercise, we need to analyze the behaviors influencing exercise participation. Interventions based on behavior change theory have been found to be significantly more successful than those that are not.”

The investigators conducted a scoping review to identify exercise barriers and facilitators in this population. They identified 23 relevant articles on intentional exercise (supervised or not and prescribed or self-initiated) among a total of 4,633 patients aged 45 years or older with hip and/or knee osteoarthritis.

Most of the more than 200 barriers and facilitators extracted from the articles were modifiable, according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The investigators mapped these modifiable factors onto domains of the Theoretical Domains Framework, which integrates multiple behavior change theories into a single framework and is aimed at helping researchers identify processes that do and do not work (Implement. Sci. 2012;7:37). They found that the barriers and facilitators mapped onto all 14 domains.

Among highlights, the many barriers mapping onto the framework’s Environmental Context and Resources domain included having to descend hills or stairs during a walking program, inability to find a suitable exercise, and rigidity of the program. Facilitators mapping onto this domain included use of a pedometer, physical therapist guidance, and receipt of a gym referral from the doctor.

Barriers mapping onto the Beliefs About Consequences domain included a belief that exercise has limited benefit, fear about damaging the joint further, and concern about precipitating pain.

Facilitators mapping onto the Reinforcement domain included medical advice to exercise, telephone reinforcement, and getting physician encouragement.

“Our findings have a number of clinical implications,” commented Ms. Nicolson.

“Given the many barriers that we identified linking to a person’s environment and resources, this highlights the need for individualized exercise tailored to each person’s situation,” she said. “Many barriers also relate to a person’s beliefs about their ability and consequences of exercise … This highlights the need for thorough and accurate education to each and every patient about their capabilities and the likely benefits of exercise.”

“Reinforcement, both internal and external, was frequently identified as a facilitator to exercise. The use of such things as logbooks, diaries, ongoing encouragement, and clinician advice to exercise can utilize these facilitators,” she concluded.

Ms. Nicolson disclosed no relevant conflicts of interest.

SEATTLE – Patients with osteoarthritis often have other common chronic conditions, a scenario that has implications for both clinical care and research, according to Dr. Gillian Hawker.

“This is a critically important topic in our field,” she told attendees of the World Congress on Osteoarthritis. “We know from myriad studies that there are major challenges to the diagnosis and management of osteoarthritis ... But probably now what’s becoming a major issue is the high occurrence of coexisting medical problems, which have been shown to present competing demands to patients and physicians who are trying to balance a number of conditions in a single patient and contraindications to osteoarthritis therapies.”

Today, 90% of individuals aged 65 years and older with osteoarthritis have at least one other chronic condition, according to Dr. Hawker, the Sir John and Lady Eaton Professor and chair of medicine at the University of Toronto. Most commonly, those conditions are cardiovascular disease, diabetes, and hypertension, but about one-third of patients have depressed mood, which may affect adherence to and effectiveness of therapies.

Two main hypotheses have been proposed for the association of osteoarthritis and other common chronic conditions, according to Dr. Hawker. According to the first hypothesis, the shared risk factors of aging and obesity independently lead to both osteoarthritis, with resultant physical inactivity, and a cluster of metabolic perturbations including hypertension, hyperglycemia, and dyslipidemia. Collectively, these conditions increase risk for cardiovascular disease and diabetes.

In support of this hypothesis, “we have lots of data from qualitative research showing that people manage their osteoarthritis symptoms by giving up activities that exacerbate them, partly because they are afraid of taking painkillers and partly because nobody offers them anything that’s more effective,” Dr. Hawker noted. In addition, when patients juggle multiple health conditions, exercise is the most frequently dropped activity.

“Many have hypothesized that inability to walk, climb stairs, and be mobile would potentially impact the ability to self-manage physical activity, impacting numerous chronic conditions,” she said. Compelling evidence comes from research such as a cohort study of patients with symptomatic hip or knee osteoarthritis that found walking disability predicted a 30% increase in the risk of all-cause death and a 17% increase in the risk of cardiovascular events; among the subset with comorbid diabetes, walking disability and grip strength predicted the risk of hospitalization for diabetic complications (PLoS One 2014;9:e91286).

“These are large, well-controlled observational studies that do show consistent independent relationships between walking disability and cardiovascular events, diabetes complications, and all-cause death,” Dr. Hawker said, while acknowledging that the research is still hypothesis generating.

Of note, recent attention has focused on systemic inflammation and a metabolic osteoarthritis phenotype. When it comes to the pathogenesis of osteoarthritis, “we now are very comfortable understanding the local biomechanical effects separately from the systemic effects on our joints,” she said. Obesity is among the systemic factors implicated, with some data suggesting that adipokines affect joint tissues in a manner similar to mechanical stress.

According to the second main hypothesis proposed to explain the association between osteoarthritis and common chronic conditions, aging and obesity give rise to a cluster of metabolic factors (hypertension, hyperglycemia, and dyslipidemia) that independently increase the risk of symptomatic osteoarthritis. Again, the arthritis may result in the loss of physical activity and disability, which exacerbates the metabolic situation.

Evidence in support of this hypothesis comes from a variety of studies. For example, one has shown that the number of components of the metabolic syndrome is related to the adjusted risk of development and progression of knee osteoarthritis (Osteoarthritis Cartilage 2012;20:1217-26).

Overall, Dr. Hawker said, “we have some independent associations between metabolic syndrome and its components, and osteoarthritis – more so in the knee and hand, more so in women than in men, and more so in younger than in older individuals. And we have some data that suggest that symptomatic and disabling osteoarthritis has an association with increased risk of cardiovascular events and diabetes complications.” Here again, the studies have limitations, so the relative contributions of disability and systemic inflammation remain unknown, she cautioned.

Hypotheses aside, the association of osteoarthritis with common chronic conditions has implications for clinical care, Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International. “Clearly, all of these data, irrespective of the relationships, point to a pivotal role for physical activity, a combination of physical activities,” she said, noting that benefits include reductions in both metabolic alterations and physical impairment, and possibly alleviation of depressed mood and improved sleep.

Osteoarthritis may be an independent risk factor for cardiovascular disease. “Many are suggesting that, in fact, if it is the fifth component of metabolic syndrome, this should really influence how we think about cardiovascular disease prevention, that osteoarthritis patients should be screened and we should be thinking more seriously about how we use various therapies,” such as nonsteroidal anti-inflammatory drugs, she said.

Dr. Hawker endorsed future research on these topics. “In the 2014 OARSI guidelines, we showed collectively as a community that we don’t have enough trials in this population, which is the majority of our patients with osteoarthritis. So yes, conservative therapy is good, but I’d say that we need way more evidence for effective interventions in the population with osteoarthritis who are living with other chronic conditions.”

Specifically needed are large prospective studies of the temporal relationships that look at mechanisms beyond age and body mass index, she explained. These studies should assess incidence and progression separately, structure and symptoms separately, and both weight-bearing and non–weight-bearing joints.

“To date, I haven’t seen any evidence to show that treatment of metabolic syndrome or its components influences the incidence or progression of osteoarthritis. And I think we should be thinking about asking those questions as they may in fact be modifiable risk factors for osteoarthritis,” she said.

Also needed are trials assessing the impact of aggressive treatment of osteoarthritis disability, according to Dr. Hawker, who disclosed that she had no relevant conflicts of interest. “If we reduce osteoarthritis disability, particularly walking disability, can we actually impact the outcomes of cardiovascular disease and diabetes? I think that’s an important question,” she concluded.

SEATTLE – Patients with osteoarthritis often have other common chronic conditions, a scenario that has implications for both clinical care and research, according to Dr. Gillian Hawker.

“This is a critically important topic in our field,” she told attendees of the World Congress on Osteoarthritis. “We know from myriad studies that there are major challenges to the diagnosis and management of osteoarthritis ... But probably now what’s becoming a major issue is the high occurrence of coexisting medical problems, which have been shown to present competing demands to patients and physicians who are trying to balance a number of conditions in a single patient and contraindications to osteoarthritis therapies.”

Today, 90% of individuals aged 65 years and older with osteoarthritis have at least one other chronic condition, according to Dr. Hawker, the Sir John and Lady Eaton Professor and chair of medicine at the University of Toronto. Most commonly, those conditions are cardiovascular disease, diabetes, and hypertension, but about one-third of patients have depressed mood, which may affect adherence to and effectiveness of therapies.

Two main hypotheses have been proposed for the association of osteoarthritis and other common chronic conditions, according to Dr. Hawker. According to the first hypothesis, the shared risk factors of aging and obesity independently lead to both osteoarthritis, with resultant physical inactivity, and a cluster of metabolic perturbations including hypertension, hyperglycemia, and dyslipidemia. Collectively, these conditions increase risk for cardiovascular disease and diabetes.

In support of this hypothesis, “we have lots of data from qualitative research showing that people manage their osteoarthritis symptoms by giving up activities that exacerbate them, partly because they are afraid of taking painkillers and partly because nobody offers them anything that’s more effective,” Dr. Hawker noted. In addition, when patients juggle multiple health conditions, exercise is the most frequently dropped activity.

“Many have hypothesized that inability to walk, climb stairs, and be mobile would potentially impact the ability to self-manage physical activity, impacting numerous chronic conditions,” she said. Compelling evidence comes from research such as a cohort study of patients with symptomatic hip or knee osteoarthritis that found walking disability predicted a 30% increase in the risk of all-cause death and a 17% increase in the risk of cardiovascular events; among the subset with comorbid diabetes, walking disability and grip strength predicted the risk of hospitalization for diabetic complications (PLoS One 2014;9:e91286).

“These are large, well-controlled observational studies that do show consistent independent relationships between walking disability and cardiovascular events, diabetes complications, and all-cause death,” Dr. Hawker said, while acknowledging that the research is still hypothesis generating.

Of note, recent attention has focused on systemic inflammation and a metabolic osteoarthritis phenotype. When it comes to the pathogenesis of osteoarthritis, “we now are very comfortable understanding the local biomechanical effects separately from the systemic effects on our joints,” she said. Obesity is among the systemic factors implicated, with some data suggesting that adipokines affect joint tissues in a manner similar to mechanical stress.

According to the second main hypothesis proposed to explain the association between osteoarthritis and common chronic conditions, aging and obesity give rise to a cluster of metabolic factors (hypertension, hyperglycemia, and dyslipidemia) that independently increase the risk of symptomatic osteoarthritis. Again, the arthritis may result in the loss of physical activity and disability, which exacerbates the metabolic situation.

Evidence in support of this hypothesis comes from a variety of studies. For example, one has shown that the number of components of the metabolic syndrome is related to the adjusted risk of development and progression of knee osteoarthritis (Osteoarthritis Cartilage 2012;20:1217-26).

Overall, Dr. Hawker said, “we have some independent associations between metabolic syndrome and its components, and osteoarthritis – more so in the knee and hand, more so in women than in men, and more so in younger than in older individuals. And we have some data that suggest that symptomatic and disabling osteoarthritis has an association with increased risk of cardiovascular events and diabetes complications.” Here again, the studies have limitations, so the relative contributions of disability and systemic inflammation remain unknown, she cautioned.

Hypotheses aside, the association of osteoarthritis with common chronic conditions has implications for clinical care, Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International. “Clearly, all of these data, irrespective of the relationships, point to a pivotal role for physical activity, a combination of physical activities,” she said, noting that benefits include reductions in both metabolic alterations and physical impairment, and possibly alleviation of depressed mood and improved sleep.

Osteoarthritis may be an independent risk factor for cardiovascular disease. “Many are suggesting that, in fact, if it is the fifth component of metabolic syndrome, this should really influence how we think about cardiovascular disease prevention, that osteoarthritis patients should be screened and we should be thinking more seriously about how we use various therapies,” such as nonsteroidal anti-inflammatory drugs, she said.

Dr. Hawker endorsed future research on these topics. “In the 2014 OARSI guidelines, we showed collectively as a community that we don’t have enough trials in this population, which is the majority of our patients with osteoarthritis. So yes, conservative therapy is good, but I’d say that we need way more evidence for effective interventions in the population with osteoarthritis who are living with other chronic conditions.”

Specifically needed are large prospective studies of the temporal relationships that look at mechanisms beyond age and body mass index, she explained. These studies should assess incidence and progression separately, structure and symptoms separately, and both weight-bearing and non–weight-bearing joints.

“To date, I haven’t seen any evidence to show that treatment of metabolic syndrome or its components influences the incidence or progression of osteoarthritis. And I think we should be thinking about asking those questions as they may in fact be modifiable risk factors for osteoarthritis,” she said.

Also needed are trials assessing the impact of aggressive treatment of osteoarthritis disability, according to Dr. Hawker, who disclosed that she had no relevant conflicts of interest. “If we reduce osteoarthritis disability, particularly walking disability, can we actually impact the outcomes of cardiovascular disease and diabetes? I think that’s an important question,” she concluded.

SEATTLE – Patients with osteoarthritis often have other common chronic conditions, a scenario that has implications for both clinical care and research, according to Dr. Gillian Hawker.

“This is a critically important topic in our field,” she told attendees of the World Congress on Osteoarthritis. “We know from myriad studies that there are major challenges to the diagnosis and management of osteoarthritis ... But probably now what’s becoming a major issue is the high occurrence of coexisting medical problems, which have been shown to present competing demands to patients and physicians who are trying to balance a number of conditions in a single patient and contraindications to osteoarthritis therapies.”

Today, 90% of individuals aged 65 years and older with osteoarthritis have at least one other chronic condition, according to Dr. Hawker, the Sir John and Lady Eaton Professor and chair of medicine at the University of Toronto. Most commonly, those conditions are cardiovascular disease, diabetes, and hypertension, but about one-third of patients have depressed mood, which may affect adherence to and effectiveness of therapies.

Two main hypotheses have been proposed for the association of osteoarthritis and other common chronic conditions, according to Dr. Hawker. According to the first hypothesis, the shared risk factors of aging and obesity independently lead to both osteoarthritis, with resultant physical inactivity, and a cluster of metabolic perturbations including hypertension, hyperglycemia, and dyslipidemia. Collectively, these conditions increase risk for cardiovascular disease and diabetes.

In support of this hypothesis, “we have lots of data from qualitative research showing that people manage their osteoarthritis symptoms by giving up activities that exacerbate them, partly because they are afraid of taking painkillers and partly because nobody offers them anything that’s more effective,” Dr. Hawker noted. In addition, when patients juggle multiple health conditions, exercise is the most frequently dropped activity.

“Many have hypothesized that inability to walk, climb stairs, and be mobile would potentially impact the ability to self-manage physical activity, impacting numerous chronic conditions,” she said. Compelling evidence comes from research such as a cohort study of patients with symptomatic hip or knee osteoarthritis that found walking disability predicted a 30% increase in the risk of all-cause death and a 17% increase in the risk of cardiovascular events; among the subset with comorbid diabetes, walking disability and grip strength predicted the risk of hospitalization for diabetic complications (PLoS One 2014;9:e91286).

“These are large, well-controlled observational studies that do show consistent independent relationships between walking disability and cardiovascular events, diabetes complications, and all-cause death,” Dr. Hawker said, while acknowledging that the research is still hypothesis generating.

Of note, recent attention has focused on systemic inflammation and a metabolic osteoarthritis phenotype. When it comes to the pathogenesis of osteoarthritis, “we now are very comfortable understanding the local biomechanical effects separately from the systemic effects on our joints,” she said. Obesity is among the systemic factors implicated, with some data suggesting that adipokines affect joint tissues in a manner similar to mechanical stress.

According to the second main hypothesis proposed to explain the association between osteoarthritis and common chronic conditions, aging and obesity give rise to a cluster of metabolic factors (hypertension, hyperglycemia, and dyslipidemia) that independently increase the risk of symptomatic osteoarthritis. Again, the arthritis may result in the loss of physical activity and disability, which exacerbates the metabolic situation.

Evidence in support of this hypothesis comes from a variety of studies. For example, one has shown that the number of components of the metabolic syndrome is related to the adjusted risk of development and progression of knee osteoarthritis (Osteoarthritis Cartilage 2012;20:1217-26).

Overall, Dr. Hawker said, “we have some independent associations between metabolic syndrome and its components, and osteoarthritis – more so in the knee and hand, more so in women than in men, and more so in younger than in older individuals. And we have some data that suggest that symptomatic and disabling osteoarthritis has an association with increased risk of cardiovascular events and diabetes complications.” Here again, the studies have limitations, so the relative contributions of disability and systemic inflammation remain unknown, she cautioned.

Hypotheses aside, the association of osteoarthritis with common chronic conditions has implications for clinical care, Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International. “Clearly, all of these data, irrespective of the relationships, point to a pivotal role for physical activity, a combination of physical activities,” she said, noting that benefits include reductions in both metabolic alterations and physical impairment, and possibly alleviation of depressed mood and improved sleep.

Osteoarthritis may be an independent risk factor for cardiovascular disease. “Many are suggesting that, in fact, if it is the fifth component of metabolic syndrome, this should really influence how we think about cardiovascular disease prevention, that osteoarthritis patients should be screened and we should be thinking more seriously about how we use various therapies,” such as nonsteroidal anti-inflammatory drugs, she said.

Dr. Hawker endorsed future research on these topics. “In the 2014 OARSI guidelines, we showed collectively as a community that we don’t have enough trials in this population, which is the majority of our patients with osteoarthritis. So yes, conservative therapy is good, but I’d say that we need way more evidence for effective interventions in the population with osteoarthritis who are living with other chronic conditions.”

Specifically needed are large prospective studies of the temporal relationships that look at mechanisms beyond age and body mass index, she explained. These studies should assess incidence and progression separately, structure and symptoms separately, and both weight-bearing and non–weight-bearing joints.

“To date, I haven’t seen any evidence to show that treatment of metabolic syndrome or its components influences the incidence or progression of osteoarthritis. And I think we should be thinking about asking those questions as they may in fact be modifiable risk factors for osteoarthritis,” she said.

Also needed are trials assessing the impact of aggressive treatment of osteoarthritis disability, according to Dr. Hawker, who disclosed that she had no relevant conflicts of interest. “If we reduce osteoarthritis disability, particularly walking disability, can we actually impact the outcomes of cardiovascular disease and diabetes? I think that’s an important question,” she concluded.

SEATTLE – New data presented at the World Congress on Osteoarthritis further suggest that hand osteoarthritis and cardiometabolic disease may have a shared etiology or pathophysiology.

In a study of 869 patients with hand osteoarthritis, those with ischemic cardiac disease were more than three times as likely to have joint symptoms and had greater clinical progression. In addition, obese patients had more extensive radiographic disease in their hands.

The results add to previous data showing higher rates of ischemic cardiac events in patients with symptomatic hand osteoarthritis (Ann. Rheum. Dis. 2013;74:74-81), according to Dr. Alice Courties, a rheumatologist at Saint-Antoine Hospital, Université Paris 6, Assistance Publique–Hôpitaux de Paris.

“One hypothesis is that symptomatic hand osteoarthritis and cardiometabolic disease share a common background based on chronic low-grade inflammation,” she proposed.

In an interview, Dr. Lisa Mandl, a rheumatologist at the Hospital for Special Surgery, New York, and one of the session’s comoderators, said, “I think this study is confirmatory that inflammation may play a role in non–weight-bearing joints.” She noted that analyses stratified by anatomic subtype of hand osteoarthritis would have been additionally informative.

Dr. Nigel Arden, the other session comoderator and director of both Musculoskeletal Epidemiology and the Oxford Musculoskeletal BioBank at the University of Oxford (England) said, “I think the whole association of cardiovascular risk, metabolic syndrome, and osteoarthritis is very important, and very important in treating patients or intervention. And this [study] is an integral part of that work.”

Giving some background to the research, Dr. Courties noted that risk factors for the development of hand osteoarthritis have been identified, but factors associated with clinical and radiographic severity of disease and with progression remain poorly defined.

The investigators performed an ancillary study of patients enrolled in the phase III, randomized Strontium Ranelate in Knee Osteoarthritis (SEKOIA) trial, in which assessments included hand x-rays and hand symptoms. The trial was conducted by Servier, but the ancillary analysis was fully independent.

Cross-sectional analyses were based on 869 patients with hand osteoarthritis, defined as presence of at least two joints with a Kellgren-Lawrence score of 2 or higher. In terms of clinical severity, 26% of patients had symptomatic hand joints, defined as a Functional Index for Hand Osteoarthritis (FIHOA) score of 5 or greater; in terms of radiographic severity, the average summary Kellgren-Lawrence hand score was 21 out of 128 points.

Results of multivariate analyses showed that patients with ischemic heart disease were more likely to have symptomatic hand joints (odds ratio, 3.59), according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International. Odds were also higher for postmenopausal women, and for patients who had depression, a higher Kellgren-Lawrence hand score, or more joints showing erosion.

Patients who were obese (a body-mass index of 30 kg/m² or greater) had more severe radiographic disease assessed with the hand score (beta, 2.88 points). Severity was also greater for those who had symptomatic hand joints or a higher Kellgren-Lawrence knee score.

Longitudinal analyses were based on the 307 patients who were in the trial’s placebo group and had a mean follow-up of 2.6 years. Overall, 23% experienced clinical progression of their hand osteoarthritis, defined as a worsening of their FIHOA, and 72% experienced radiographic progression, defined as a worsening of their Kellgren-Lawrence hand score, reported Dr. Courties, who disclosed that she has received congress invitations from Pfizer, Biogaran, and Expanscience. Multivariate analysis here showed that patients with ischemic cardiac disease had greater clinical progression (beta, 2.31 points), while those with a higher hand score at baseline had greater radiographic progression.

SEATTLE – New data presented at the World Congress on Osteoarthritis further suggest that hand osteoarthritis and cardiometabolic disease may have a shared etiology or pathophysiology.

In a study of 869 patients with hand osteoarthritis, those with ischemic cardiac disease were more than three times as likely to have joint symptoms and had greater clinical progression. In addition, obese patients had more extensive radiographic disease in their hands.

The results add to previous data showing higher rates of ischemic cardiac events in patients with symptomatic hand osteoarthritis (Ann. Rheum. Dis. 2013;74:74-81), according to Dr. Alice Courties, a rheumatologist at Saint-Antoine Hospital, Université Paris 6, Assistance Publique–Hôpitaux de Paris.

“One hypothesis is that symptomatic hand osteoarthritis and cardiometabolic disease share a common background based on chronic low-grade inflammation,” she proposed.

In an interview, Dr. Lisa Mandl, a rheumatologist at the Hospital for Special Surgery, New York, and one of the session’s comoderators, said, “I think this study is confirmatory that inflammation may play a role in non–weight-bearing joints.” She noted that analyses stratified by anatomic subtype of hand osteoarthritis would have been additionally informative.

Dr. Nigel Arden, the other session comoderator and director of both Musculoskeletal Epidemiology and the Oxford Musculoskeletal BioBank at the University of Oxford (England) said, “I think the whole association of cardiovascular risk, metabolic syndrome, and osteoarthritis is very important, and very important in treating patients or intervention. And this [study] is an integral part of that work.”

Giving some background to the research, Dr. Courties noted that risk factors for the development of hand osteoarthritis have been identified, but factors associated with clinical and radiographic severity of disease and with progression remain poorly defined.

The investigators performed an ancillary study of patients enrolled in the phase III, randomized Strontium Ranelate in Knee Osteoarthritis (SEKOIA) trial, in which assessments included hand x-rays and hand symptoms. The trial was conducted by Servier, but the ancillary analysis was fully independent.

Cross-sectional analyses were based on 869 patients with hand osteoarthritis, defined as presence of at least two joints with a Kellgren-Lawrence score of 2 or higher. In terms of clinical severity, 26% of patients had symptomatic hand joints, defined as a Functional Index for Hand Osteoarthritis (FIHOA) score of 5 or greater; in terms of radiographic severity, the average summary Kellgren-Lawrence hand score was 21 out of 128 points.

Results of multivariate analyses showed that patients with ischemic heart disease were more likely to have symptomatic hand joints (odds ratio, 3.59), according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International. Odds were also higher for postmenopausal women, and for patients who had depression, a higher Kellgren-Lawrence hand score, or more joints showing erosion.

Patients who were obese (a body-mass index of 30 kg/m² or greater) had more severe radiographic disease assessed with the hand score (beta, 2.88 points). Severity was also greater for those who had symptomatic hand joints or a higher Kellgren-Lawrence knee score.

Longitudinal analyses were based on the 307 patients who were in the trial’s placebo group and had a mean follow-up of 2.6 years. Overall, 23% experienced clinical progression of their hand osteoarthritis, defined as a worsening of their FIHOA, and 72% experienced radiographic progression, defined as a worsening of their Kellgren-Lawrence hand score, reported Dr. Courties, who disclosed that she has received congress invitations from Pfizer, Biogaran, and Expanscience. Multivariate analysis here showed that patients with ischemic cardiac disease had greater clinical progression (beta, 2.31 points), while those with a higher hand score at baseline had greater radiographic progression.

SEATTLE – New data presented at the World Congress on Osteoarthritis further suggest that hand osteoarthritis and cardiometabolic disease may have a shared etiology or pathophysiology.

In a study of 869 patients with hand osteoarthritis, those with ischemic cardiac disease were more than three times as likely to have joint symptoms and had greater clinical progression. In addition, obese patients had more extensive radiographic disease in their hands.

The results add to previous data showing higher rates of ischemic cardiac events in patients with symptomatic hand osteoarthritis (Ann. Rheum. Dis. 2013;74:74-81), according to Dr. Alice Courties, a rheumatologist at Saint-Antoine Hospital, Université Paris 6, Assistance Publique–Hôpitaux de Paris.

“One hypothesis is that symptomatic hand osteoarthritis and cardiometabolic disease share a common background based on chronic low-grade inflammation,” she proposed.

In an interview, Dr. Lisa Mandl, a rheumatologist at the Hospital for Special Surgery, New York, and one of the session’s comoderators, said, “I think this study is confirmatory that inflammation may play a role in non–weight-bearing joints.” She noted that analyses stratified by anatomic subtype of hand osteoarthritis would have been additionally informative.

Dr. Nigel Arden, the other session comoderator and director of both Musculoskeletal Epidemiology and the Oxford Musculoskeletal BioBank at the University of Oxford (England) said, “I think the whole association of cardiovascular risk, metabolic syndrome, and osteoarthritis is very important, and very important in treating patients or intervention. And this [study] is an integral part of that work.”

Giving some background to the research, Dr. Courties noted that risk factors for the development of hand osteoarthritis have been identified, but factors associated with clinical and radiographic severity of disease and with progression remain poorly defined.

The investigators performed an ancillary study of patients enrolled in the phase III, randomized Strontium Ranelate in Knee Osteoarthritis (SEKOIA) trial, in which assessments included hand x-rays and hand symptoms. The trial was conducted by Servier, but the ancillary analysis was fully independent.

Cross-sectional analyses were based on 869 patients with hand osteoarthritis, defined as presence of at least two joints with a Kellgren-Lawrence score of 2 or higher. In terms of clinical severity, 26% of patients had symptomatic hand joints, defined as a Functional Index for Hand Osteoarthritis (FIHOA) score of 5 or greater; in terms of radiographic severity, the average summary Kellgren-Lawrence hand score was 21 out of 128 points.

Results of multivariate analyses showed that patients with ischemic heart disease were more likely to have symptomatic hand joints (odds ratio, 3.59), according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International. Odds were also higher for postmenopausal women, and for patients who had depression, a higher Kellgren-Lawrence hand score, or more joints showing erosion.

Patients who were obese (a body-mass index of 30 kg/m² or greater) had more severe radiographic disease assessed with the hand score (beta, 2.88 points). Severity was also greater for those who had symptomatic hand joints or a higher Kellgren-Lawrence knee score.

Longitudinal analyses were based on the 307 patients who were in the trial’s placebo group and had a mean follow-up of 2.6 years. Overall, 23% experienced clinical progression of their hand osteoarthritis, defined as a worsening of their FIHOA, and 72% experienced radiographic progression, defined as a worsening of their Kellgren-Lawrence hand score, reported Dr. Courties, who disclosed that she has received congress invitations from Pfizer, Biogaran, and Expanscience. Multivariate analysis here showed that patients with ischemic cardiac disease had greater clinical progression (beta, 2.31 points), while those with a higher hand score at baseline had greater radiographic progression.

SEATTLE – Heavier individuals are more likely to have degenerative changes of the lumbar spine seen on MRI, according to findings from an analysis of 1,684 patients in the European Genodisc Study.

“BMI [body mass index] is associated with disc herniation and spinal stenosis. It is also associated with disc degeneration, but the coefficient is so small it’s unlikely to be clinically relevant,” lead investigator Dr. Anand Segar reported at the World Congress on Osteoarthritis.

“Age appears to be the most import factor in determining spinal degeneration,” he added. “Interestingly, smoking and work intensity were not associated with any outcomes.”

Although degenerative changes were worse and more prevalent at the lower lumbar levels, the associations of BMI with these changes were actually stronger at the upper three levels, according to Dr. Segar, who is a resident in the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England). Thus, “we further add to the thought of an upper spine phenotype, which has been described by other authors, and this needs further investigation,” he maintained.

Session comoderator Dr. Jeffrey N. Katz, professor of orthopedic surgery at Harvard Medical School and codirector of the Brigham Spine Center at Brigham and Women’s Hospital, Boston, asked, “Looking at the upper spine, were you able to exclude the possibility of scoliosis as a reason for transferring load to the upper rather than the lower spine? And in evaluating spinal stenosis and thinking about BMI as your primary predictor, did you make any accommodation for how you dealt with epidural fat in relation to spinal stenosis?”

The investigators did not specifically look at scoliosis, but it was uncommon in the study sample and therefore unlikely to have affected the findings, Dr. Segar replied. Similarly, they did not specifically evaluate epidural fat, “but my understanding from the literature is that epidural fat is not really associated with obesity, ... so I don’t think again it would have changed our results.”

The patients in Genodisc were recruited from tertiary spinal clinics in the United Kingdom, Hungary, Italy, and Slovenia.

They underwent MRI of the lumbar spine, and the scans were evaluated by a musculoskeletal radiologist. Disc degeneration was assessed with the 5-point Pfirrmann grading system, while disc herniation and spinal stenosis were simply scored as present or absent.

On average, the patients studied were 51 years old and had a BMI of 27.2 kg/m², according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Results of multivariate analysis showed that each 5-kg/m² increase in BMI was associated with a 0.04-unit increase in disc degeneration score, a 19% increase in the odds of disc herniation, and a 24% increase in the odds of spinal stenosis.

For comparison, each 10-year increment in age was associated with a 0.31-unit increase in disc degeneration score, a 30% decrease in the odds of disc herniation, and a more than a doubling of the odds of spinal stenosis.

The impact of BMI on the lumbar spine was greater at the upper three levels, reported Dr. Segar, who disclosed no relevant conflicts of interest. In analyses restricted to those levels, each 5-kg/m² increase in BMI was associated with a 39% increase in the odds of disc herniation and a 65% increase in the odds of spinal stenosis.

SEATTLE – Heavier individuals are more likely to have degenerative changes of the lumbar spine seen on MRI, according to findings from an analysis of 1,684 patients in the European Genodisc Study.

“BMI [body mass index] is associated with disc herniation and spinal stenosis. It is also associated with disc degeneration, but the coefficient is so small it’s unlikely to be clinically relevant,” lead investigator Dr. Anand Segar reported at the World Congress on Osteoarthritis.

“Age appears to be the most import factor in determining spinal degeneration,” he added. “Interestingly, smoking and work intensity were not associated with any outcomes.”

Although degenerative changes were worse and more prevalent at the lower lumbar levels, the associations of BMI with these changes were actually stronger at the upper three levels, according to Dr. Segar, who is a resident in the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England). Thus, “we further add to the thought of an upper spine phenotype, which has been described by other authors, and this needs further investigation,” he maintained.

Session comoderator Dr. Jeffrey N. Katz, professor of orthopedic surgery at Harvard Medical School and codirector of the Brigham Spine Center at Brigham and Women’s Hospital, Boston, asked, “Looking at the upper spine, were you able to exclude the possibility of scoliosis as a reason for transferring load to the upper rather than the lower spine? And in evaluating spinal stenosis and thinking about BMI as your primary predictor, did you make any accommodation for how you dealt with epidural fat in relation to spinal stenosis?”

The investigators did not specifically look at scoliosis, but it was uncommon in the study sample and therefore unlikely to have affected the findings, Dr. Segar replied. Similarly, they did not specifically evaluate epidural fat, “but my understanding from the literature is that epidural fat is not really associated with obesity, ... so I don’t think again it would have changed our results.”

The patients in Genodisc were recruited from tertiary spinal clinics in the United Kingdom, Hungary, Italy, and Slovenia.

They underwent MRI of the lumbar spine, and the scans were evaluated by a musculoskeletal radiologist. Disc degeneration was assessed with the 5-point Pfirrmann grading system, while disc herniation and spinal stenosis were simply scored as present or absent.

On average, the patients studied were 51 years old and had a BMI of 27.2 kg/m², according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Results of multivariate analysis showed that each 5-kg/m² increase in BMI was associated with a 0.04-unit increase in disc degeneration score, a 19% increase in the odds of disc herniation, and a 24% increase in the odds of spinal stenosis.

For comparison, each 10-year increment in age was associated with a 0.31-unit increase in disc degeneration score, a 30% decrease in the odds of disc herniation, and a more than a doubling of the odds of spinal stenosis.

The impact of BMI on the lumbar spine was greater at the upper three levels, reported Dr. Segar, who disclosed no relevant conflicts of interest. In analyses restricted to those levels, each 5-kg/m² increase in BMI was associated with a 39% increase in the odds of disc herniation and a 65% increase in the odds of spinal stenosis.

SEATTLE – Heavier individuals are more likely to have degenerative changes of the lumbar spine seen on MRI, according to findings from an analysis of 1,684 patients in the European Genodisc Study.

“BMI [body mass index] is associated with disc herniation and spinal stenosis. It is also associated with disc degeneration, but the coefficient is so small it’s unlikely to be clinically relevant,” lead investigator Dr. Anand Segar reported at the World Congress on Osteoarthritis.

“Age appears to be the most import factor in determining spinal degeneration,” he added. “Interestingly, smoking and work intensity were not associated with any outcomes.”

Although degenerative changes were worse and more prevalent at the lower lumbar levels, the associations of BMI with these changes were actually stronger at the upper three levels, according to Dr. Segar, who is a resident in the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England). Thus, “we further add to the thought of an upper spine phenotype, which has been described by other authors, and this needs further investigation,” he maintained.

Session comoderator Dr. Jeffrey N. Katz, professor of orthopedic surgery at Harvard Medical School and codirector of the Brigham Spine Center at Brigham and Women’s Hospital, Boston, asked, “Looking at the upper spine, were you able to exclude the possibility of scoliosis as a reason for transferring load to the upper rather than the lower spine? And in evaluating spinal stenosis and thinking about BMI as your primary predictor, did you make any accommodation for how you dealt with epidural fat in relation to spinal stenosis?”

The investigators did not specifically look at scoliosis, but it was uncommon in the study sample and therefore unlikely to have affected the findings, Dr. Segar replied. Similarly, they did not specifically evaluate epidural fat, “but my understanding from the literature is that epidural fat is not really associated with obesity, ... so I don’t think again it would have changed our results.”

The patients in Genodisc were recruited from tertiary spinal clinics in the United Kingdom, Hungary, Italy, and Slovenia.

They underwent MRI of the lumbar spine, and the scans were evaluated by a musculoskeletal radiologist. Disc degeneration was assessed with the 5-point Pfirrmann grading system, while disc herniation and spinal stenosis were simply scored as present or absent.

On average, the patients studied were 51 years old and had a BMI of 27.2 kg/m², according to data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Results of multivariate analysis showed that each 5-kg/m² increase in BMI was associated with a 0.04-unit increase in disc degeneration score, a 19% increase in the odds of disc herniation, and a 24% increase in the odds of spinal stenosis.

For comparison, each 10-year increment in age was associated with a 0.31-unit increase in disc degeneration score, a 30% decrease in the odds of disc herniation, and a more than a doubling of the odds of spinal stenosis.

The impact of BMI on the lumbar spine was greater at the upper three levels, reported Dr. Segar, who disclosed no relevant conflicts of interest. In analyses restricted to those levels, each 5-kg/m² increase in BMI was associated with a 39% increase in the odds of disc herniation and a 65% increase in the odds of spinal stenosis.