Will Pass

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.

copyright claudiobaba/iStockPhoto.com

Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.

“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.

This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”

The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).

Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).

At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.

The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).

In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).

The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”

The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.

“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”

The investigators reported having no financial disclosures.

SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.

Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.

copyright claudiobaba/iStockPhoto.com

Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.

“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.

This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”

The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).

Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).

At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.

The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).

In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).

The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”

The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.

“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”

The investigators reported having no financial disclosures.

SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.

Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.

copyright claudiobaba/iStockPhoto.com

Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.

“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.

This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”

The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).

Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).

At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.

The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).

In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).

The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”

The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.

“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”

The investigators reported having no financial disclosures.

SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.

Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.

“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.

Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.

“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”

One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.

“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.

The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.

On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.

“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”

GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.

To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.

As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.

“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.

Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”

Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”

Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”

Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.

“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”

Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
 

SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

MUNICH – Patients with HIV who are treated with nivolumab, a programmed death-1 (PD-1) inhibitor, appear to have similar safety and efficacy outcomes compared with HIV-negative patients treated with the same agent, investigators found.

The retrospective study also showed that viral load and CD4 status were largely unchanged by immunotherapy, lead author Aurélien Gobert, MD, of Groupe Hospitalier Pitié Salpêtrière, Paris, reported at the European Society for Medical Oncology Congress.

HIV increases risks of certain cancer types, Dr. Gobert said in a press release. “These patients are at higher risk for a number of cancers: AIDS-defining forms, the diagnosis of which results in the categorization of a person as suffering from AIDS, but also various other types that they are two to three times more likely to develop than in the general population, such as anal, skin, head and neck, and lung cancer,” he said.

Despite the increased risks, few studies have evaluated cancer treatments for patients with HIV due to exclusions from most clinical trials. As HIV is an immune-based disease, concerns have arisen surrounding the safety and efficacy of using anti-neoplastic immunotherapies for HIV-positive patients. Considering that millions of people worldwide are HIV positive, research in this area can have real-world consequences.

Dr. Gobert and his colleagues analyzed data from CANCERVIH, a French national database of patients with cancer and HIV. Since May 2014, nivolumab has been administered to 20 patients. Nineteen had metastatic non–small-cell lung cancer and 1 had metastatic melanoma. At diagnosis, the median CD4 count was 338.5 per cubic millimeter. Seventeen patients had undetectable viral load, two had fewer than 40 copies per millimeter, and one patient’s viral load was unknown. Dr. Gobert described the population as “demographically homogenous,” with “most patients being males around 60 years old.”

Analysis showed that nivolumab had little impact on CD4 count or viral load. One patient had a decreased CD4 count and an increased viral load, but this occurred during an interruption to antiretroviral therapy, which clouds potential associations with nivolumab. No immune-related adverse events or deaths due to drug toxicity occurred. Efficacy was assessed in 17 patients: Four (24%) showed a partial response, 2 (12%) had stable disease, and 11 (64%) had disease progression.

“Based on these preliminary data, treatment with anti-PD-1 ... seems to be feasible in people with HIV,” Dr. Gobert reported. He added that “antiretroviral therapy should not be interrupted.”

In a comment for ESMO, John Haanen, PhD, of the Netherlands Cancer Institute, Amsterdam, said that the results “confirm those of other, smaller cohorts in showing that while on antiretroviral therapy, cancer patients living with HIV can safely receive anti-PD-1 treatment. The efficacy data also suggests that the overall response rate of HIV-positive patients seems to be similar to that of other cancer patients. These promising results need to be confirmed in larger studies – ideally, in a prospective clinical trial.”

Principal investigator Jean-Philippe Spano, MD, PhD, disclosed relationships with Gilead, Roche, BMS, and others.

SOURCE: Gobert et al. ESMO 2018, Abstract 1213P_PR.

MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.

Will Pass/MDedge News

The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.

Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.

“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.

“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.

The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).

The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.

The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.

Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”

Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”

As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”

Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).

SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
 

SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.

MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.

Will Pass/MDedge News

The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.

Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.

“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.

“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.

The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).

The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.

The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.

Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”

Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”

As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”

Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).

SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
 

SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.

MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.

Will Pass/MDedge News

The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.

Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.

“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.

“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.

The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).

The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.

The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.

Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”

Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”

As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”

Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).

SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
 

SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.

MUNICH – Neoadjuvant erlotinib for patients with stage IIIA (N2) non–small cell lung cancer (NSCLC) increased progression-free survival (PFS), compared with gemcitabine and cisplatin, according to results from the recent CTONG 1103 trial.

Will Pass/MDedge News

Despite beating chemotherapy, erlotinib, an epithelial growth factor receptor (EGFR)–mutant tyrosine kinase inhibitor (TKI), fell short of benchmarks set by adjuvant therapy, so it is unlikely that neoadjuvant erlotinib will see clinical use anytime soon.

Lead author Wen-Zhao Zhong, MD, PhD, of Guangdong Lung Cancer Institute and Guangdong General Hospital in Guangzhou, China, presenting at the European Society for Medical Oncology Congress, said that the recent findings support further investigation into biomarker-guided neoadjuvant therapy for stage IIIA (N2) NSCLC, as identifying patient subgroups could potentially improve outcomes.

Principal investigator Yi-Long Wu, MD, described the impetus for CTONG 1103 in an interview. “Recently, the CTONG 1104 trial showed for the first time that adjuvant EGFR-TKI gefitinib could improve disease-free survival ... compared to adjuvant chemotherapy ... in N1N2-resected NSCLC. This raises the possibility that EGFR-TKIs may play a beneficial role in the neoadjuvant setting for this subgroup,” he said.

CTONG 1103 is an ongoing, phase 2, open-label trial. Out of 386 patients screened, 72 were enrolled based on treatment naivety and EGFR mutation positivity (exon 19 or 21). Following randomization, patients received either erlotinib 150 mg daily for 42 days or gemcitabine 1,250 mg/m² (days 1 and 8) and cisplatin 75 mg/m2 (day 1) every 3 weeks for two cycles. After surgery, patients in the erlotinib group continued therapy for 1 year, while patients in the chemotherapy cohort received two more cycles of treatment.

The primary endpoint was objective response rate, and secondary endpoints included PFS, pathological lymph node downstaging, overall survival, safety measures, and complete pathological response. The investigators also highlighted major pathological response (less than 10% viable cancer cells after preoperative therapy).

The results showed that about half of the patients receiving erlotinib had an objective response (54.1%), compared with approximately one-third in the chemotherapy group (34.3%); however, this difference was not statistically significant (P = .092). Erlotinib also provided a median PFS nearly twice that of chemotherapy (21.5 months vs. 11.9 months; P = .003) and more frequent lymph node downstaging (10.8% vs. 2.9%), but no patients achieved complete pathological response. The number of patients achieving major pathological response with erlotinib was limited but still more than chemotherapy (10.7% vs. 0%). The investigators are awaiting an overall survival rate.

Erlotinib showed similar adverse events to previous trials, most commonly, rash, diarrhea, cough, and oral ulcers, compared with chemotherapy, which was associated with GI issues, hematologic disturbances, and fatigue.

Will Pass/MDedge News

In response to these findings, Suresh S. Ramalingam, MD, invited discussant and deputy director of the Winship Cancer Institute of Emory University, Atlanta, first discussed relevant efficacy measures. “The best predictor of long-term outcomes in these patients is nodal downstaging,” Dr. Ramalingam said. In previous studies, “patients who had clearance of the nodes had the best outcomes, and that continues to be an important prognostic marker.”

While major pathological response is valuable, and previous studies have revealed prognostic value, evidence is too limited to suggest that this is equivalent with cure, and it should not be considered as significant as complete pathological response, he said.

Considering that “only 11% of the patients” treated with erlotinib had nodal downstaging and/or major pathological response, and none achieved complete pathological response, Dr. Ramalingam suggested that the results were modest at best.

“While erlotinib seems to be doing better than chemo, I feel that the chemo group here is underperforming, compared to historical controls,” Dr. Ramalingam said, noting higher benchmark objective response rates (61% vs. 34%) and complete pathological response rates (4% vs. 0%).

Instead of focusing on neoadjuvant studies, Dr. Ramalingam suggested that ongoing adjuvant trials (ALCHEMIST and ADAURA) hold more promise and are more likely to serve as inroads for TKIs like erlotinib.

“Adjuvant care has withstood the test of time,” Dr. Ramalingam said. “Neoadjuvant EGFR-TKI in N2 disease I don’t think is ready for center stage.”

CTONG 1103 was sponsored by CTONG and Roche. The authors reported financial affiliations with AstraZeneca, Pfizer, Roche, and others. Dr. Ramalingam reported compensation from Amgen, Bristol-Myers Squibb, Loxo Oncology, and others.

MUNICH – Neoadjuvant erlotinib for patients with stage IIIA (N2) non–small cell lung cancer (NSCLC) increased progression-free survival (PFS), compared with gemcitabine and cisplatin, according to results from the recent CTONG 1103 trial.

Will Pass/MDedge News

Despite beating chemotherapy, erlotinib, an epithelial growth factor receptor (EGFR)–mutant tyrosine kinase inhibitor (TKI), fell short of benchmarks set by adjuvant therapy, so it is unlikely that neoadjuvant erlotinib will see clinical use anytime soon.

Lead author Wen-Zhao Zhong, MD, PhD, of Guangdong Lung Cancer Institute and Guangdong General Hospital in Guangzhou, China, presenting at the European Society for Medical Oncology Congress, said that the recent findings support further investigation into biomarker-guided neoadjuvant therapy for stage IIIA (N2) NSCLC, as identifying patient subgroups could potentially improve outcomes.

Principal investigator Yi-Long Wu, MD, described the impetus for CTONG 1103 in an interview. “Recently, the CTONG 1104 trial showed for the first time that adjuvant EGFR-TKI gefitinib could improve disease-free survival ... compared to adjuvant chemotherapy ... in N1N2-resected NSCLC. This raises the possibility that EGFR-TKIs may play a beneficial role in the neoadjuvant setting for this subgroup,” he said.

CTONG 1103 is an ongoing, phase 2, open-label trial. Out of 386 patients screened, 72 were enrolled based on treatment naivety and EGFR mutation positivity (exon 19 or 21). Following randomization, patients received either erlotinib 150 mg daily for 42 days or gemcitabine 1,250 mg/m² (days 1 and 8) and cisplatin 75 mg/m2 (day 1) every 3 weeks for two cycles. After surgery, patients in the erlotinib group continued therapy for 1 year, while patients in the chemotherapy cohort received two more cycles of treatment.

The primary endpoint was objective response rate, and secondary endpoints included PFS, pathological lymph node downstaging, overall survival, safety measures, and complete pathological response. The investigators also highlighted major pathological response (less than 10% viable cancer cells after preoperative therapy).

The results showed that about half of the patients receiving erlotinib had an objective response (54.1%), compared with approximately one-third in the chemotherapy group (34.3%); however, this difference was not statistically significant (P = .092). Erlotinib also provided a median PFS nearly twice that of chemotherapy (21.5 months vs. 11.9 months; P = .003) and more frequent lymph node downstaging (10.8% vs. 2.9%), but no patients achieved complete pathological response. The number of patients achieving major pathological response with erlotinib was limited but still more than chemotherapy (10.7% vs. 0%). The investigators are awaiting an overall survival rate.

Erlotinib showed similar adverse events to previous trials, most commonly, rash, diarrhea, cough, and oral ulcers, compared with chemotherapy, which was associated with GI issues, hematologic disturbances, and fatigue.

Will Pass/MDedge News

In response to these findings, Suresh S. Ramalingam, MD, invited discussant and deputy director of the Winship Cancer Institute of Emory University, Atlanta, first discussed relevant efficacy measures. “The best predictor of long-term outcomes in these patients is nodal downstaging,” Dr. Ramalingam said. In previous studies, “patients who had clearance of the nodes had the best outcomes, and that continues to be an important prognostic marker.”

While major pathological response is valuable, and previous studies have revealed prognostic value, evidence is too limited to suggest that this is equivalent with cure, and it should not be considered as significant as complete pathological response, he said.

Considering that “only 11% of the patients” treated with erlotinib had nodal downstaging and/or major pathological response, and none achieved complete pathological response, Dr. Ramalingam suggested that the results were modest at best.

“While erlotinib seems to be doing better than chemo, I feel that the chemo group here is underperforming, compared to historical controls,” Dr. Ramalingam said, noting higher benchmark objective response rates (61% vs. 34%) and complete pathological response rates (4% vs. 0%).

Instead of focusing on neoadjuvant studies, Dr. Ramalingam suggested that ongoing adjuvant trials (ALCHEMIST and ADAURA) hold more promise and are more likely to serve as inroads for TKIs like erlotinib.

“Adjuvant care has withstood the test of time,” Dr. Ramalingam said. “Neoadjuvant EGFR-TKI in N2 disease I don’t think is ready for center stage.”

CTONG 1103 was sponsored by CTONG and Roche. The authors reported financial affiliations with AstraZeneca, Pfizer, Roche, and others. Dr. Ramalingam reported compensation from Amgen, Bristol-Myers Squibb, Loxo Oncology, and others.

MUNICH – Neoadjuvant erlotinib for patients with stage IIIA (N2) non–small cell lung cancer (NSCLC) increased progression-free survival (PFS), compared with gemcitabine and cisplatin, according to results from the recent CTONG 1103 trial.

Will Pass/MDedge News

Despite beating chemotherapy, erlotinib, an epithelial growth factor receptor (EGFR)–mutant tyrosine kinase inhibitor (TKI), fell short of benchmarks set by adjuvant therapy, so it is unlikely that neoadjuvant erlotinib will see clinical use anytime soon.

Lead author Wen-Zhao Zhong, MD, PhD, of Guangdong Lung Cancer Institute and Guangdong General Hospital in Guangzhou, China, presenting at the European Society for Medical Oncology Congress, said that the recent findings support further investigation into biomarker-guided neoadjuvant therapy for stage IIIA (N2) NSCLC, as identifying patient subgroups could potentially improve outcomes.

Principal investigator Yi-Long Wu, MD, described the impetus for CTONG 1103 in an interview. “Recently, the CTONG 1104 trial showed for the first time that adjuvant EGFR-TKI gefitinib could improve disease-free survival ... compared to adjuvant chemotherapy ... in N1N2-resected NSCLC. This raises the possibility that EGFR-TKIs may play a beneficial role in the neoadjuvant setting for this subgroup,” he said.

CTONG 1103 is an ongoing, phase 2, open-label trial. Out of 386 patients screened, 72 were enrolled based on treatment naivety and EGFR mutation positivity (exon 19 or 21). Following randomization, patients received either erlotinib 150 mg daily for 42 days or gemcitabine 1,250 mg/m² (days 1 and 8) and cisplatin 75 mg/m2 (day 1) every 3 weeks for two cycles. After surgery, patients in the erlotinib group continued therapy for 1 year, while patients in the chemotherapy cohort received two more cycles of treatment.

The primary endpoint was objective response rate, and secondary endpoints included PFS, pathological lymph node downstaging, overall survival, safety measures, and complete pathological response. The investigators also highlighted major pathological response (less than 10% viable cancer cells after preoperative therapy).

The results showed that about half of the patients receiving erlotinib had an objective response (54.1%), compared with approximately one-third in the chemotherapy group (34.3%); however, this difference was not statistically significant (P = .092). Erlotinib also provided a median PFS nearly twice that of chemotherapy (21.5 months vs. 11.9 months; P = .003) and more frequent lymph node downstaging (10.8% vs. 2.9%), but no patients achieved complete pathological response. The number of patients achieving major pathological response with erlotinib was limited but still more than chemotherapy (10.7% vs. 0%). The investigators are awaiting an overall survival rate.

Erlotinib showed similar adverse events to previous trials, most commonly, rash, diarrhea, cough, and oral ulcers, compared with chemotherapy, which was associated with GI issues, hematologic disturbances, and fatigue.

Will Pass/MDedge News

In response to these findings, Suresh S. Ramalingam, MD, invited discussant and deputy director of the Winship Cancer Institute of Emory University, Atlanta, first discussed relevant efficacy measures. “The best predictor of long-term outcomes in these patients is nodal downstaging,” Dr. Ramalingam said. In previous studies, “patients who had clearance of the nodes had the best outcomes, and that continues to be an important prognostic marker.”

While major pathological response is valuable, and previous studies have revealed prognostic value, evidence is too limited to suggest that this is equivalent with cure, and it should not be considered as significant as complete pathological response, he said.

Considering that “only 11% of the patients” treated with erlotinib had nodal downstaging and/or major pathological response, and none achieved complete pathological response, Dr. Ramalingam suggested that the results were modest at best.

“While erlotinib seems to be doing better than chemo, I feel that the chemo group here is underperforming, compared to historical controls,” Dr. Ramalingam said, noting higher benchmark objective response rates (61% vs. 34%) and complete pathological response rates (4% vs. 0%).

Instead of focusing on neoadjuvant studies, Dr. Ramalingam suggested that ongoing adjuvant trials (ALCHEMIST and ADAURA) hold more promise and are more likely to serve as inroads for TKIs like erlotinib.

“Adjuvant care has withstood the test of time,” Dr. Ramalingam said. “Neoadjuvant EGFR-TKI in N2 disease I don’t think is ready for center stage.”

CTONG 1103 was sponsored by CTONG and Roche. The authors reported financial affiliations with AstraZeneca, Pfizer, Roche, and others. Dr. Ramalingam reported compensation from Amgen, Bristol-Myers Squibb, Loxo Oncology, and others.

MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.

Neil Osterweil/MDedge News

“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.

HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.

Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.

“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.

ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).

The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.

The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.

These tolerability issues were expected, however, based on previous chidamide findings.

Neil Osterweil/MDedge News

“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.

“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”

In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.

Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.

To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”

The ACE trial was funded by Chipscreen Biosciences.

SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.

MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.

Neil Osterweil/MDedge News

“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.

HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.

Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.

“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.

ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).

The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.

The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.

These tolerability issues were expected, however, based on previous chidamide findings.

Neil Osterweil/MDedge News

“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.

“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”

In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.

Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.

To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”

The ACE trial was funded by Chipscreen Biosciences.

SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.

MUNICH – For patients with HR-positive (HR+) and human epidermal growth factor receptor 2 (HER2)–advanced breast cancer who have progressed after endocrine therapy, a combination of the oral histone deacetylase (HDAC) inhibitor chidamide and exemestane appears safe and more effective than exemestane alone, according to results from the phase 3 ACE trial.

Neil Osterweil/MDedge News

“This is the first phase 3 trial to demonstrate that an HDAC inhibitor plus endocrine blockade improves progression-free survival, compared to endocrine blockade alone in hormone receptor positive advanced breast cancer patients who have progressed after prior endocrine therapy,” said lead author, Zefei Jiang, MD, at the European Society for Medical Oncology Congress.

HDAC inhibitors have historically been used for psychiatric and neurologic applications, but interest in their antineoplastic potential has increased over the past decade. Chidamide is approved for T-cell lymphoma in China, but not in the United States, where three other HDAC inhibitors are labeled for T-cell lymphoma, and a fourth is approved for multiple myeloma.

Although no HDAC inhibitors are clinically available for breast cancer, the future may tell a different story. The HDAC inhibitor entinostat received a breakthrough therapy designation by the Food and Drug Administration after the phase 2 ENCORE 301 trial showed clinical benefit (also with exemestane for advanced breast cancer). Ongoing studies are also evaluating the potential for HDAC inhibitors in combination with immunotherapy.

“Histone modulation by HDACs is a very important mechanism for epigenetic regulation,” said Dr. Jiang, of the 307th Hospital of Chinese People’s Liberation Army in Beijing, highlighting associations with breast cancer drug resistance. HDAC inhibition may be able to overcome this obstacle by resensitizing tumors to estrogen modulator therapy.

ACE was a double-blind, placebo-controlled study involving 362 patients with HR+/HER2–advanced breast cancer who failed endocrine therapy. Patients had previously received no more than one round of chemotherapy for advanced disease, and no more than four therapies total. The treatment group received either chidamide 30 mg twice weekly with exemestane 25 mg daily (n = 241) or exemestane with placebo (n = 121). Tumor assessments were performed every 8 weeks, and the primary endpoint was progression-free survival (PFS).

The addition of chidamide nearly doubled PFS (7.4 months vs. 3.8 months) and provided a hazard ratio of .75 (P = .0336). Objective response and clinical benefit rates also were increased. At the time of presentation, data were too immature for an overall survival rate.

The most common grade 3 or higher adverse events were hematologic: neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%), all considerably higher than 2.5% for each in the placebo group.

These tolerability issues were expected, however, based on previous chidamide findings.

Neil Osterweil/MDedge News

“Not surprisingly ... 33% of patients had their dose reduced, 50% their dose interrupted, and this is despite the biweekly schedule,” said invited discussant Rebecca Dent, MD, of the National Cancer Centre in Singapore. Despite these issues, Dr. Dent concluded that chidamide otherwise “appears to be quite well tolerated,” and showed meaningful results.

“We now have a second trial demonstrating ... clinical benefit from the addition of HDAC inhibitors to endocrine therapy in [HR+] advanced breast cancer,” Dr. Dent said. “HDAC inhibitors clearly warrant further investigation in earlier settings of [HR+] advanced breast cancer and ... yet to be defined ... subgroups, and obviously we anxiously await the phase 3 results of entinostat.”

In consideration of the future, Dr. Dent suggested that more studies are needed to develop subgroup-targeted therapies and optimize sequencing. “We’ve really underestimated the selective pressure of these treatments and how they impact our subsequent therapies,” she said.

Dr. Dent noted how these factors limit predictive relevance of study findings in clinical practice, in which patients with different treatment histories may have completely different responses to the same agent.

To overcome these obstacles, Dr. Dent encouraged development of biomarker-driven strategies that can identify unique patterns of drug resistance and sensitivity. “This will allow us to ... identify which patients, which drug, and at which time.”

The ACE trial was funded by Chipscreen Biosciences.

SOURCE: Jiang Z et al. ESMO 2018, Abstract 283O.

Moderate hypofractionation is preferred over conventional fractionation in treatment of patients with localized prostate cancer who are candidates for external beam radiotherapy (EBRT), according to new a clinical practice guideline.

A meta-analysis of randomized clinical trials showed that moderate fractionation delivered the same efficacy as did conventional fractionation with a mild increase in gastrointestinal toxicity, reported lead author Scott C. Morgan, MD of OSF Medical Group in Bloomington, Illinois, and his colleagues. The drawback of toxicity is outweighed by distinct advantages in resource utilization and patient convenience, which make moderate hypofractionation the winning choice.

For many types of cancer, a shift toward fewer fractions of higher radiation is ongoing, driven largely by technological advances in radiation planning and delivery.

“Technical advances have permitted more precise and conformal delivery of escalated doses of radiation to the prostate, thereby improving the therapeutic ratio,” the authors wrote in the Journal of Clinical Oncology.

Fractionation is typically limited by adjacent tissue sensitivity, but prostate tumors are more sensitive to radiation than the rectum, allowing for higher doses of radiation without damaging healthy tissue. While conventional fractionation doses are between 180 and 200 cGy, moderate hypofractionation delivers doses of 240-340 cGy. Ultrahypofractionation is defined by doses equal to or greater than 500 cGy (the upper limit of the linear-quadratic model of cell survival).

The present guideline was developed through a 2-year, collaborative effort between the American Society of Radiation Oncology, the Society of Clinical Oncology, and the American Urological Association. Task force members included urologic surgeons and oncologists, medical physicists, and radiation oncologists from academic and nonacademic settings. A patient representative and radiation oncology resident also were involved. After completing a systematic literature review, the team developed recommendations with varying degrees of strength. Supporting evidence quality and level of consensus also were described.

Of note, the guideline calls for moderate hypofractionation for patients with localized prostate cancer regardless of urinary function, anatomy, comorbidity, or age, with or without radiation to the seminal vesicles. Along with this recommendation, clinicians should discuss with patients the small increased risk of acute gastrointestinal toxicity, compared with conventional fractionation and the limited follow-up time in most relevant clinical trials (often less than 5 years).

The guideline conveyed more skepticism regarding ultrahypofractionation because of a lack of supporting evidence and comparative trials. As such, the authors conditionally recommended ultrahypofractionation for low-risk and intermediate patients, the latter of whom should be encouraged to enter clinical trials.

“The conditional recommendations regarding ultrahypofractionation underscore the importance of shared decision making between clinicians and patients in this setting,” the authors wrote. “The decision to use ultrahypofractionated EBRT at this time should follow a detailed discussion of the existing uncertainties in the risk-benefit balance associated with this treatment approach and should be informed at all stages by the patient’s values and preferences.”

The authors reported financial affiliations with Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others.

SOURCE: Morgan et al. J Clin Oncol. 2018 Oct 11. doi: 10.1200/JCO.18.01097.

Moderate hypofractionation is preferred over conventional fractionation in treatment of patients with localized prostate cancer who are candidates for external beam radiotherapy (EBRT), according to new a clinical practice guideline.

A meta-analysis of randomized clinical trials showed that moderate fractionation delivered the same efficacy as did conventional fractionation with a mild increase in gastrointestinal toxicity, reported lead author Scott C. Morgan, MD of OSF Medical Group in Bloomington, Illinois, and his colleagues. The drawback of toxicity is outweighed by distinct advantages in resource utilization and patient convenience, which make moderate hypofractionation the winning choice.

For many types of cancer, a shift toward fewer fractions of higher radiation is ongoing, driven largely by technological advances in radiation planning and delivery.

“Technical advances have permitted more precise and conformal delivery of escalated doses of radiation to the prostate, thereby improving the therapeutic ratio,” the authors wrote in the Journal of Clinical Oncology.

Fractionation is typically limited by adjacent tissue sensitivity, but prostate tumors are more sensitive to radiation than the rectum, allowing for higher doses of radiation without damaging healthy tissue. While conventional fractionation doses are between 180 and 200 cGy, moderate hypofractionation delivers doses of 240-340 cGy. Ultrahypofractionation is defined by doses equal to or greater than 500 cGy (the upper limit of the linear-quadratic model of cell survival).

The present guideline was developed through a 2-year, collaborative effort between the American Society of Radiation Oncology, the Society of Clinical Oncology, and the American Urological Association. Task force members included urologic surgeons and oncologists, medical physicists, and radiation oncologists from academic and nonacademic settings. A patient representative and radiation oncology resident also were involved. After completing a systematic literature review, the team developed recommendations with varying degrees of strength. Supporting evidence quality and level of consensus also were described.

Of note, the guideline calls for moderate hypofractionation for patients with localized prostate cancer regardless of urinary function, anatomy, comorbidity, or age, with or without radiation to the seminal vesicles. Along with this recommendation, clinicians should discuss with patients the small increased risk of acute gastrointestinal toxicity, compared with conventional fractionation and the limited follow-up time in most relevant clinical trials (often less than 5 years).

The guideline conveyed more skepticism regarding ultrahypofractionation because of a lack of supporting evidence and comparative trials. As such, the authors conditionally recommended ultrahypofractionation for low-risk and intermediate patients, the latter of whom should be encouraged to enter clinical trials.

“The conditional recommendations regarding ultrahypofractionation underscore the importance of shared decision making between clinicians and patients in this setting,” the authors wrote. “The decision to use ultrahypofractionated EBRT at this time should follow a detailed discussion of the existing uncertainties in the risk-benefit balance associated with this treatment approach and should be informed at all stages by the patient’s values and preferences.”

The authors reported financial affiliations with Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others.

SOURCE: Morgan et al. J Clin Oncol. 2018 Oct 11. doi: 10.1200/JCO.18.01097.

Moderate hypofractionation is preferred over conventional fractionation in treatment of patients with localized prostate cancer who are candidates for external beam radiotherapy (EBRT), according to new a clinical practice guideline.

A meta-analysis of randomized clinical trials showed that moderate fractionation delivered the same efficacy as did conventional fractionation with a mild increase in gastrointestinal toxicity, reported lead author Scott C. Morgan, MD of OSF Medical Group in Bloomington, Illinois, and his colleagues. The drawback of toxicity is outweighed by distinct advantages in resource utilization and patient convenience, which make moderate hypofractionation the winning choice.

For many types of cancer, a shift toward fewer fractions of higher radiation is ongoing, driven largely by technological advances in radiation planning and delivery.

“Technical advances have permitted more precise and conformal delivery of escalated doses of radiation to the prostate, thereby improving the therapeutic ratio,” the authors wrote in the Journal of Clinical Oncology.

Fractionation is typically limited by adjacent tissue sensitivity, but prostate tumors are more sensitive to radiation than the rectum, allowing for higher doses of radiation without damaging healthy tissue. While conventional fractionation doses are between 180 and 200 cGy, moderate hypofractionation delivers doses of 240-340 cGy. Ultrahypofractionation is defined by doses equal to or greater than 500 cGy (the upper limit of the linear-quadratic model of cell survival).

The present guideline was developed through a 2-year, collaborative effort between the American Society of Radiation Oncology, the Society of Clinical Oncology, and the American Urological Association. Task force members included urologic surgeons and oncologists, medical physicists, and radiation oncologists from academic and nonacademic settings. A patient representative and radiation oncology resident also were involved. After completing a systematic literature review, the team developed recommendations with varying degrees of strength. Supporting evidence quality and level of consensus also were described.

Of note, the guideline calls for moderate hypofractionation for patients with localized prostate cancer regardless of urinary function, anatomy, comorbidity, or age, with or without radiation to the seminal vesicles. Along with this recommendation, clinicians should discuss with patients the small increased risk of acute gastrointestinal toxicity, compared with conventional fractionation and the limited follow-up time in most relevant clinical trials (often less than 5 years).

The guideline conveyed more skepticism regarding ultrahypofractionation because of a lack of supporting evidence and comparative trials. As such, the authors conditionally recommended ultrahypofractionation for low-risk and intermediate patients, the latter of whom should be encouraged to enter clinical trials.

“The conditional recommendations regarding ultrahypofractionation underscore the importance of shared decision making between clinicians and patients in this setting,” the authors wrote. “The decision to use ultrahypofractionated EBRT at this time should follow a detailed discussion of the existing uncertainties in the risk-benefit balance associated with this treatment approach and should be informed at all stages by the patient’s values and preferences.”

The authors reported financial affiliations with Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others.

SOURCE: Morgan et al. J Clin Oncol. 2018 Oct 11. doi: 10.1200/JCO.18.01097.

Image by Betty Pace

Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.

Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.

Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.

The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.

Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.

The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.

Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.

Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.

Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.

In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.

In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.

In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.

Safety was comparable across subgroups.

This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.

Image by Betty Pace

Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.

Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.

Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.

The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.

Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.

The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.

Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.

Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.

Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.

In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.

In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.

In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.

Safety was comparable across subgroups.

This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.

Image by Betty Pace

Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.

Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.

Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.

The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.

Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.

The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.

Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.

Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.

Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.

In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.

In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.

In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.

Safety was comparable across subgroups.

This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.