Hodgkin Lymphoma

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.

The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.

Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).

Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.

copyright varaphoto/Thinkstock

Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.

The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.

Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).

Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.

copyright varaphoto/Thinkstock

Children who had developed inflammatory bowel disease had an 18-fold greater risk of gastrointestinal cancers in later life, a new study suggests.

The cohort study found that the risk of all cancers was elevated in individuals with childhood-onset inflammatory bowel disease, but particularly in those with primary sclerosing cholangitis and ulcerative colitis.

Researchers followed 9,405 patients with childhood-onset inflammatory bowel disease to a mean age of 27 years using a Swedish national patient register (BMJ. 2017 Sep 21. doi: 10.1136/bmj.j3951).

Analysis revealed that individuals with childhood-onset inflammatory bowel disease had double the risk of any cancer, compared with the general population (hazard ratio, 2.2; 95% confidence interval, 2.0-2.5), and a 2.7-fold greater risk of developing cancer before the age of 18 years.

copyright varaphoto/Thinkstock

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Esther Dyson

ATLANTA—New research suggests some racial/ethnic minority groups are underrepresented in clinical trials for cancer patients in the US.

African-American and Hispanic patients were underrepresented in the trials studied, while Asian and non-Hispanic white patients were not.

Patients belonging to other racial/ethnic groups were not studied in detail.

The research also showed that elderly patients were less likely than other age groups to enroll in a cancer trial.

However, the percentage of elderly patients in the trials studied (36%) was more than double the percentage of elderly individuals in the US population (15.2%).

This research was presented at the 10th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (abstract A26).

“Clinical trials are crucial in studying the effectiveness of new drugs and ultimately bringing them to the market to benefit patients,” said Narjust Duma, MD, of the Mayo Clinic in Rochester, Minnesota.

“However, many clinical trials lack appropriate representation of certain patient populations. As a result, the findings of a clinical trial might not be generalizable to all patients.”

Dr Duma and her colleagues analyzed enrollment data from all cancer therapeutic trials reported as completed on clinicaltrials.gov from 2003 to 2016. These trials included 55,689 subjects, and the racial/ethnic breakdown of the group was as follows:

• Non-Hispanic white—83%
• African-American—6%
• Asian—5.3%
• Hispanic—2.6%
• “Other”—2.4%.

According to the US Census Bureau, as of July 1, 2016, the estimated total US population was 323,127,516. The racial/ethnic breakdown of that population is as follows:

• White alone (excluding Hispanics/Latinos)—61.3%
• Hispanic/Latino*—17.8%
• Black/African-American alone—13.3%
• Asian alone—5.7%
• American Indian/Alaska Native—1.3%
• Native Hawaiian/Other Pacific Islander—0.2%
• Two or more races—2.6%.

Dr Duma and her colleagues said their study suggests African-American and Hispanic representation in cancer trials has declined in recent years, when compared to historical data from 1996 to 2002.

In the 1996-2002 period, African-Americans represented 9.2% of patients in cancer trials (vs 6% in 2003-2016), and Hispanics represented 3.1% (vs 2.6% in 2003-2016).

On the other hand, the recruitment of Asians in cancer trials has more than doubled, from 2% in the historical data to 5.3% in the current data.

The current study also showed that elderly patients (age 65 and older) represented 36% of the subjects enrolled in cancer trials. In comparison, 15.2% of the total US population is 65 or older.

Previous research suggested the elderly are often underrepresented in clinical trials, despite the fact that most cancer cases are diagnosed in individuals age 65 and older, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results database.

Dr Duma said the increasing use of genetic information in clinical trials may be decreasing the numbers of ethnic minorities and elderly patients. In recent years, researchers have sought to study drugs that treat cancers by targeting certain mutations. In order to identify the patients who are most likely to respond to the drugs, many trials now require molecular testing of tumors.

“This is leading to significant advances,” Dr Duma said. “However, it is vastly more expensive to run these trials, often leaving a limited budget to recruit patients or do outreach to the elderly or minorities.”

“Also, this type of testing can only be conducted at the major cancer centers. The mid-sized, regional hospitals are excluded because they don’t have the capacity, and, sadly, this leaves us farther away from these populations.”

Dr Duma added that cultural biases may also make minorities less likely to enroll in clinical trials. Previous research has indicated that members of certain minority groups may be less likely to trust healthcare providers.

Language barriers may also be a factor for minority patients, and the elderly may be dissuaded by difficulty in traveling to and from major cancer centers, Dr Duma noted.

She identified a few potential ways to narrow the gap of participation in clinical trials:

• Increase clinical trial partnerships between major cancer centers and satellite hospitals. Dr Duma suggested that patients could be enrolled at their local hospital and undergo treatment there, while data could be sent to the partnering cancer center.
• Targeted interventions, such as Spanish interpreters, could be used to help enroll minority patients in clinical trials.
• Healthcare providers should be mindful of the need to enroll more patients from underrepresented populations and should be willing to discuss risks and benefits with patients.

Dr Duma said the main limitation of this study is that race and ethnicity are generally self-reported, which could lead to some inconsistencies in data.

*The US Census Bureau notes that Hispanics may be of any race, so they are also included in applicable race categories.

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.