Amy Karon

Switching from natalizumab to fingolimod kept 85% of multiple sclerosis patients relapse-free for at least 6 months in an observational cohort study.

Although relapse rates remained low after patients started fingolimod, patients who had a gap of 2-4 months between cessation of prior treatment and commencement of fingolimod had significantly higher relapse rates than did those with no treatment gap.

"The main risk factor for time to relapse on fingolimod was recent prior relapse," said Dr. Vilija Jokubaitis of the University of Melbourne and her associates. "Our data support choosing a short switch period (2 months or less) between prior treatment and fingolimod to decrease the hazard of relapse," they added.

Because of concerns about progressive multifocal leukoencephalopathy (PML), patients with multiple sclerosis (MS) often are switched to fingolimod (Gilenya) if they have taken natalizumab (Tysabri) for more than 24 months and test positive for anti-JC virus antibodies. To evaluate the effects of switching on MS relapse, the researchers studied 536 patients from the MSBase Registry who took fingolimod as initial therapy (n = 97), switched to fingolimod after failing natalizumab (n = 89), or switched to fingolimod from interferon-beta/glatiramer acetate (n = 350). The median washout period for patients switching from natalizumab to fingolimod was 79 days (interquartile range, 57-96 days), and the median follow-up for all patients was 10.3 months, the investigators reported (Neurology 2014 March 7 [doi: 10.1212/WNL.0000000000000283]).

Relapse rates were "relatively stable" among the patients who switched from natalizumab to fingolimod during the first 9 months on fingolimod (quarterly relapse rate range, 0.079-0.13), compared with the 15-month period before starting fingolimod (quarterly relapse rate range, 0.05-0.11). Patients who switched from natalizumab to fingolimod had a small increase in annualized relapse rate (0.38 vs. 0.26 for natalizumab; P = .002), which the investigators attributed to possible differences in efficacy between the two medications. In survival analyses, predictors of time to first relapse on fingolimod included number of relapses in the past 6 months (hazard ratio, 1.60 per relapse; P = .002) and a treatment gap of 2-4 months vs. no gap (HR, 2.10; P = .041).

"In this study, the largest of its kind to date, we found no evidence to support the occurrence of clinical rebound in patients switching from natalizumab to fingolimod," wrote Dr. Jokubaitis and her associates. Relapse activity was well-controlled in this patient group, and it was similar to relapse activity in patients switching to fingolimod from interferon-beta/glatiramer acetate or those starting fingolimod as their first disease-modifying therapy for MS.

The study was funded by a grant from the Australian National Health and Medical Research Council and by the MSBase Foundation. Dr. Jokubaitis and 13 of her associates reported having received honoraria or other support from Novartis, which makes fingolimod. Ten associates reported receiving honoraria or other support from Biogen Idec, which makes natalizumab.

Switching from natalizumab to fingolimod kept 85% of multiple sclerosis patients relapse-free for at least 6 months in an observational cohort study.

Although relapse rates remained low after patients started fingolimod, patients who had a gap of 2-4 months between cessation of prior treatment and commencement of fingolimod had significantly higher relapse rates than did those with no treatment gap.

"The main risk factor for time to relapse on fingolimod was recent prior relapse," said Dr. Vilija Jokubaitis of the University of Melbourne and her associates. "Our data support choosing a short switch period (2 months or less) between prior treatment and fingolimod to decrease the hazard of relapse," they added.

Because of concerns about progressive multifocal leukoencephalopathy (PML), patients with multiple sclerosis (MS) often are switched to fingolimod (Gilenya) if they have taken natalizumab (Tysabri) for more than 24 months and test positive for anti-JC virus antibodies. To evaluate the effects of switching on MS relapse, the researchers studied 536 patients from the MSBase Registry who took fingolimod as initial therapy (n = 97), switched to fingolimod after failing natalizumab (n = 89), or switched to fingolimod from interferon-beta/glatiramer acetate (n = 350). The median washout period for patients switching from natalizumab to fingolimod was 79 days (interquartile range, 57-96 days), and the median follow-up for all patients was 10.3 months, the investigators reported (Neurology 2014 March 7 [doi: 10.1212/WNL.0000000000000283]).

Relapse rates were "relatively stable" among the patients who switched from natalizumab to fingolimod during the first 9 months on fingolimod (quarterly relapse rate range, 0.079-0.13), compared with the 15-month period before starting fingolimod (quarterly relapse rate range, 0.05-0.11). Patients who switched from natalizumab to fingolimod had a small increase in annualized relapse rate (0.38 vs. 0.26 for natalizumab; P = .002), which the investigators attributed to possible differences in efficacy between the two medications. In survival analyses, predictors of time to first relapse on fingolimod included number of relapses in the past 6 months (hazard ratio, 1.60 per relapse; P = .002) and a treatment gap of 2-4 months vs. no gap (HR, 2.10; P = .041).

"In this study, the largest of its kind to date, we found no evidence to support the occurrence of clinical rebound in patients switching from natalizumab to fingolimod," wrote Dr. Jokubaitis and her associates. Relapse activity was well-controlled in this patient group, and it was similar to relapse activity in patients switching to fingolimod from interferon-beta/glatiramer acetate or those starting fingolimod as their first disease-modifying therapy for MS.

The study was funded by a grant from the Australian National Health and Medical Research Council and by the MSBase Foundation. Dr. Jokubaitis and 13 of her associates reported having received honoraria or other support from Novartis, which makes fingolimod. Ten associates reported receiving honoraria or other support from Biogen Idec, which makes natalizumab.

Switching from natalizumab to fingolimod kept 85% of multiple sclerosis patients relapse-free for at least 6 months in an observational cohort study.

Although relapse rates remained low after patients started fingolimod, patients who had a gap of 2-4 months between cessation of prior treatment and commencement of fingolimod had significantly higher relapse rates than did those with no treatment gap.

"The main risk factor for time to relapse on fingolimod was recent prior relapse," said Dr. Vilija Jokubaitis of the University of Melbourne and her associates. "Our data support choosing a short switch period (2 months or less) between prior treatment and fingolimod to decrease the hazard of relapse," they added.

Because of concerns about progressive multifocal leukoencephalopathy (PML), patients with multiple sclerosis (MS) often are switched to fingolimod (Gilenya) if they have taken natalizumab (Tysabri) for more than 24 months and test positive for anti-JC virus antibodies. To evaluate the effects of switching on MS relapse, the researchers studied 536 patients from the MSBase Registry who took fingolimod as initial therapy (n = 97), switched to fingolimod after failing natalizumab (n = 89), or switched to fingolimod from interferon-beta/glatiramer acetate (n = 350). The median washout period for patients switching from natalizumab to fingolimod was 79 days (interquartile range, 57-96 days), and the median follow-up for all patients was 10.3 months, the investigators reported (Neurology 2014 March 7 [doi: 10.1212/WNL.0000000000000283]).

Relapse rates were "relatively stable" among the patients who switched from natalizumab to fingolimod during the first 9 months on fingolimod (quarterly relapse rate range, 0.079-0.13), compared with the 15-month period before starting fingolimod (quarterly relapse rate range, 0.05-0.11). Patients who switched from natalizumab to fingolimod had a small increase in annualized relapse rate (0.38 vs. 0.26 for natalizumab; P = .002), which the investigators attributed to possible differences in efficacy between the two medications. In survival analyses, predictors of time to first relapse on fingolimod included number of relapses in the past 6 months (hazard ratio, 1.60 per relapse; P = .002) and a treatment gap of 2-4 months vs. no gap (HR, 2.10; P = .041).

"In this study, the largest of its kind to date, we found no evidence to support the occurrence of clinical rebound in patients switching from natalizumab to fingolimod," wrote Dr. Jokubaitis and her associates. Relapse activity was well-controlled in this patient group, and it was similar to relapse activity in patients switching to fingolimod from interferon-beta/glatiramer acetate or those starting fingolimod as their first disease-modifying therapy for MS.

The study was funded by a grant from the Australian National Health and Medical Research Council and by the MSBase Foundation. Dr. Jokubaitis and 13 of her associates reported having received honoraria or other support from Novartis, which makes fingolimod. Ten associates reported receiving honoraria or other support from Biogen Idec, which makes natalizumab.

Only 0.19% of cholecystectomy patients had incidental gallbladder cancer, and incidence was just 0.03% in patients who lacked risk factors for the malignancy, according to investigators. The report was published in Annals of Surgery.

The results were lower than historical reports, probably because cholecystectomy has been increasingly performed in younger patients, said Dr. Susan Pitt of Washington University, St. Louis, and her associates.

The investigators reported that significant risk factors for incidental gall bladder cancer (iGBC) included open (vs. laparoscopic) cholecystectomy, older age, Asian or African-American race, female sex, and an elevated alkaline phosphatase (ALP) level (Ann. Surg. 2014 Feb. 6 [doi:10.1097/SLA.0000000000000485]).

The retrospective cohort study included 91,260 patients aged 16 years and older who underwent laparoscopic (n = 80,924 [88.7%]) or open (n = 10,336 [11.3%]) cholecystectomy from 2005 to 2009. Patients were identified through the American College of Surgeons-National Surgical Quality Improvement Program Participant Use File.

Only 0.05% of laparoscopic patients had iGBC, vs. 0.60% of laparoscopic converted to open cholecystectomy patients (P less than .001) and 1.13% of open cholecystectomy patients (P less than .001), the researchers said. Multivariable predictors for iGBC included open vs. laparoscopic approach (odds ratio, 12.0; 95% confidence interval, 8.5-16.7); age 65 years or older (OR, 5.3; 95% CI, 3.7-7.4); Asian (OR, 2.2; 95% CI, 1.1-4.4) or African-American race (OR, 1.7; 95% CI, 1.1-2.6); alkaline phosphatase level 120 units/L or greater (OR, 1.7; 95% CI, 1.3-2.3); and female sex (OR, 1.6; 95% CI, 1.1-2.2).

"Even in the presence of all these risk factors, the incidence of iGBC is only 1.4%, although it is nearly 50-fold higher than a patient without any risk factors," Dr. Pitt and her associates wrote. Identifying patients at risk of iGBC before surgery "might allow a surgeon to be prepared to perform an adequate R0 resection at the initial procedure or refer the patient to a center with expertise in liver surgery, especially in the presence of a gallbladder polyp or mass on imaging," they added.

Within 30 days of surgery, patients with iGBC had significantly higher rates of death, serious morbidity, overall morbidity, surgical site infection, and organ space surgical site infection (P less than .001 for all outcomes), the researchers reported.

The study database lacked information on symptoms, preoperative diagnoses, or diagnostic studies specific to gallbladder disease, Dr. Pitt and her coworkers noted. The large sample size increased the possibility of type I error because small differences might reach statistical significance even if they lacked clinical importance, they added.

The authors received no funding for the study. One of the investigators, Dr. Bruce Hall, is a paid consultant for the American College of Surgeons.

Only 0.19% of cholecystectomy patients had incidental gallbladder cancer, and incidence was just 0.03% in patients who lacked risk factors for the malignancy, according to investigators. The report was published in Annals of Surgery.

The results were lower than historical reports, probably because cholecystectomy has been increasingly performed in younger patients, said Dr. Susan Pitt of Washington University, St. Louis, and her associates.

The investigators reported that significant risk factors for incidental gall bladder cancer (iGBC) included open (vs. laparoscopic) cholecystectomy, older age, Asian or African-American race, female sex, and an elevated alkaline phosphatase (ALP) level (Ann. Surg. 2014 Feb. 6 [doi:10.1097/SLA.0000000000000485]).

The retrospective cohort study included 91,260 patients aged 16 years and older who underwent laparoscopic (n = 80,924 [88.7%]) or open (n = 10,336 [11.3%]) cholecystectomy from 2005 to 2009. Patients were identified through the American College of Surgeons-National Surgical Quality Improvement Program Participant Use File.

Only 0.05% of laparoscopic patients had iGBC, vs. 0.60% of laparoscopic converted to open cholecystectomy patients (P less than .001) and 1.13% of open cholecystectomy patients (P less than .001), the researchers said. Multivariable predictors for iGBC included open vs. laparoscopic approach (odds ratio, 12.0; 95% confidence interval, 8.5-16.7); age 65 years or older (OR, 5.3; 95% CI, 3.7-7.4); Asian (OR, 2.2; 95% CI, 1.1-4.4) or African-American race (OR, 1.7; 95% CI, 1.1-2.6); alkaline phosphatase level 120 units/L or greater (OR, 1.7; 95% CI, 1.3-2.3); and female sex (OR, 1.6; 95% CI, 1.1-2.2).

"Even in the presence of all these risk factors, the incidence of iGBC is only 1.4%, although it is nearly 50-fold higher than a patient without any risk factors," Dr. Pitt and her associates wrote. Identifying patients at risk of iGBC before surgery "might allow a surgeon to be prepared to perform an adequate R0 resection at the initial procedure or refer the patient to a center with expertise in liver surgery, especially in the presence of a gallbladder polyp or mass on imaging," they added.

Within 30 days of surgery, patients with iGBC had significantly higher rates of death, serious morbidity, overall morbidity, surgical site infection, and organ space surgical site infection (P less than .001 for all outcomes), the researchers reported.

The study database lacked information on symptoms, preoperative diagnoses, or diagnostic studies specific to gallbladder disease, Dr. Pitt and her coworkers noted. The large sample size increased the possibility of type I error because small differences might reach statistical significance even if they lacked clinical importance, they added.

The authors received no funding for the study. One of the investigators, Dr. Bruce Hall, is a paid consultant for the American College of Surgeons.

Only 0.19% of cholecystectomy patients had incidental gallbladder cancer, and incidence was just 0.03% in patients who lacked risk factors for the malignancy, according to investigators. The report was published in Annals of Surgery.

The results were lower than historical reports, probably because cholecystectomy has been increasingly performed in younger patients, said Dr. Susan Pitt of Washington University, St. Louis, and her associates.

The investigators reported that significant risk factors for incidental gall bladder cancer (iGBC) included open (vs. laparoscopic) cholecystectomy, older age, Asian or African-American race, female sex, and an elevated alkaline phosphatase (ALP) level (Ann. Surg. 2014 Feb. 6 [doi:10.1097/SLA.0000000000000485]).

The retrospective cohort study included 91,260 patients aged 16 years and older who underwent laparoscopic (n = 80,924 [88.7%]) or open (n = 10,336 [11.3%]) cholecystectomy from 2005 to 2009. Patients were identified through the American College of Surgeons-National Surgical Quality Improvement Program Participant Use File.

Only 0.05% of laparoscopic patients had iGBC, vs. 0.60% of laparoscopic converted to open cholecystectomy patients (P less than .001) and 1.13% of open cholecystectomy patients (P less than .001), the researchers said. Multivariable predictors for iGBC included open vs. laparoscopic approach (odds ratio, 12.0; 95% confidence interval, 8.5-16.7); age 65 years or older (OR, 5.3; 95% CI, 3.7-7.4); Asian (OR, 2.2; 95% CI, 1.1-4.4) or African-American race (OR, 1.7; 95% CI, 1.1-2.6); alkaline phosphatase level 120 units/L or greater (OR, 1.7; 95% CI, 1.3-2.3); and female sex (OR, 1.6; 95% CI, 1.1-2.2).

"Even in the presence of all these risk factors, the incidence of iGBC is only 1.4%, although it is nearly 50-fold higher than a patient without any risk factors," Dr. Pitt and her associates wrote. Identifying patients at risk of iGBC before surgery "might allow a surgeon to be prepared to perform an adequate R0 resection at the initial procedure or refer the patient to a center with expertise in liver surgery, especially in the presence of a gallbladder polyp or mass on imaging," they added.

Within 30 days of surgery, patients with iGBC had significantly higher rates of death, serious morbidity, overall morbidity, surgical site infection, and organ space surgical site infection (P less than .001 for all outcomes), the researchers reported.

The study database lacked information on symptoms, preoperative diagnoses, or diagnostic studies specific to gallbladder disease, Dr. Pitt and her coworkers noted. The large sample size increased the possibility of type I error because small differences might reach statistical significance even if they lacked clinical importance, they added.

The authors received no funding for the study. One of the investigators, Dr. Bruce Hall, is a paid consultant for the American College of Surgeons.

Ten-year follow-up of patients from EORTC trial 22921 confirmed that fluorouracil-based chemotherapy after preoperative radiotherapy did not affect survival in patients with rectal cancer, according to researchers.

The results were the same whether or not patients also received preoperative chemotherapy, reported Jean-François Bosset of Besançon University Hospital J Minjoz, France, and his associates.

EORTC trial 22921 enrolled 1,011 patients with resectable T3 or T4 M0 rectal adenocarcinoma. Investigators randomized patients to four treatment arms – preoperative radiotherapy alone, preoperative radiotherapy and chemotherapy, preoperative radiotherapy followed by adjuvant chemotherapy, and preoperative radiotherapy plus chemotherapy followed by adjuvant chemotherapy (Lancet Oncol. 2014;15:184-90).

The chemotherapy course included fluorouracil (350 mg/m² per day IV) and leucovorin (20 mg/m² per day IV). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. Radiotherapy lasted 5 weeks and consisted of 45 Gy to the posterior pelvis in 1.8-Gy fractions.

After a median follow-up of 10.4 years, overall survival did not differ significantly among the four treatment groups, ranging from 48.4% to 51.9%. Disease-free survival rates also did not differ significantly, ranging from 44.2% to 47.0%. Most recurrences occurred within 5 years, with no significant differences in frequencies of distal metastases and long-term side effects.

Only 43% of patients randomized to adjuvant chemotherapy received the planned dose within the allocated time period, the investigators reported. Such poor adherence might have hampered the ability to assess the value of adjuvant chemotherapy in rectal cancer, they said, adding that "adherence to adjuvant chemotherapy and a preserved dose-intensity over all the cycles will be the crucial issue that will potentially determine the success of these approaches."

The study was supported by EORTC, the National Cancer Institute, Programme Hospitalier de Recherche Clinique, and Ligue contre le Cancer Comité du Doubs. The authors reported that they had no conflicts of interest.

tor@frontlinemedcom.com

Ten-year follow-up of patients from EORTC trial 22921 confirmed that fluorouracil-based chemotherapy after preoperative radiotherapy did not affect survival in patients with rectal cancer, according to researchers.

The results were the same whether or not patients also received preoperative chemotherapy, reported Jean-François Bosset of Besançon University Hospital J Minjoz, France, and his associates.

EORTC trial 22921 enrolled 1,011 patients with resectable T3 or T4 M0 rectal adenocarcinoma. Investigators randomized patients to four treatment arms – preoperative radiotherapy alone, preoperative radiotherapy and chemotherapy, preoperative radiotherapy followed by adjuvant chemotherapy, and preoperative radiotherapy plus chemotherapy followed by adjuvant chemotherapy (Lancet Oncol. 2014;15:184-90).

The chemotherapy course included fluorouracil (350 mg/m² per day IV) and leucovorin (20 mg/m² per day IV). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. Radiotherapy lasted 5 weeks and consisted of 45 Gy to the posterior pelvis in 1.8-Gy fractions.

After a median follow-up of 10.4 years, overall survival did not differ significantly among the four treatment groups, ranging from 48.4% to 51.9%. Disease-free survival rates also did not differ significantly, ranging from 44.2% to 47.0%. Most recurrences occurred within 5 years, with no significant differences in frequencies of distal metastases and long-term side effects.

Only 43% of patients randomized to adjuvant chemotherapy received the planned dose within the allocated time period, the investigators reported. Such poor adherence might have hampered the ability to assess the value of adjuvant chemotherapy in rectal cancer, they said, adding that "adherence to adjuvant chemotherapy and a preserved dose-intensity over all the cycles will be the crucial issue that will potentially determine the success of these approaches."

The study was supported by EORTC, the National Cancer Institute, Programme Hospitalier de Recherche Clinique, and Ligue contre le Cancer Comité du Doubs. The authors reported that they had no conflicts of interest.

tor@frontlinemedcom.com

Ten-year follow-up of patients from EORTC trial 22921 confirmed that fluorouracil-based chemotherapy after preoperative radiotherapy did not affect survival in patients with rectal cancer, according to researchers.

The results were the same whether or not patients also received preoperative chemotherapy, reported Jean-François Bosset of Besançon University Hospital J Minjoz, France, and his associates.

EORTC trial 22921 enrolled 1,011 patients with resectable T3 or T4 M0 rectal adenocarcinoma. Investigators randomized patients to four treatment arms – preoperative radiotherapy alone, preoperative radiotherapy and chemotherapy, preoperative radiotherapy followed by adjuvant chemotherapy, and preoperative radiotherapy plus chemotherapy followed by adjuvant chemotherapy (Lancet Oncol. 2014;15:184-90).

The chemotherapy course included fluorouracil (350 mg/m² per day IV) and leucovorin (20 mg/m² per day IV). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. Radiotherapy lasted 5 weeks and consisted of 45 Gy to the posterior pelvis in 1.8-Gy fractions.

After a median follow-up of 10.4 years, overall survival did not differ significantly among the four treatment groups, ranging from 48.4% to 51.9%. Disease-free survival rates also did not differ significantly, ranging from 44.2% to 47.0%. Most recurrences occurred within 5 years, with no significant differences in frequencies of distal metastases and long-term side effects.

Only 43% of patients randomized to adjuvant chemotherapy received the planned dose within the allocated time period, the investigators reported. Such poor adherence might have hampered the ability to assess the value of adjuvant chemotherapy in rectal cancer, they said, adding that "adherence to adjuvant chemotherapy and a preserved dose-intensity over all the cycles will be the crucial issue that will potentially determine the success of these approaches."

The study was supported by EORTC, the National Cancer Institute, Programme Hospitalier de Recherche Clinique, and Ligue contre le Cancer Comité du Doubs. The authors reported that they had no conflicts of interest.

tor@frontlinemedcom.com

Genomic abnormalities can be identified in individual patients with metastatic breast cancer, which can then lead to targeted therapy, investigators reported in the March issue of Lancet Oncology.

In a prospective study of 423 patients who had breast cancer with a metastasis accessible for biopsy, comparative genomic hybridization array was feasible in 283 patients and Sanger sequencing was feasible in 297 patients. A targetable genomic alteration was found in 195 patients (46%), most often PIK3CA mutation (25%), CCND1 amplification (18%), and FGFR1 amplification (12%), reported Dr. Fabrice André of Institut Gustave Roussy, Villejuif, France, and his associates.

The primary endpoint – the ability to offer targeted therapy based on genomic sequencing – was achieved for 55 patients (13%). Of the 43 patients who ultimately received targeted therapy as a result of the genomic analyses, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Grade 3 or higher adverse events related to biopsy were reported in four patients (Lancet Oncol. 2014;15:267-74).

The response rate was "disappointing," but the patient population had been heavily pretreated, the researchers noted.

The result "justifies the development of multiple strategies to improve efficacy of screening" for targeted therapy, the investigators said. They recommended improving algorithms for analyzing genomic data, using highly bioactive agents for targeted therapy, and combining therapies to delay drug resistance.

The study was sponsored by the French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, and Operation Parrains Chercheurs. The authors reported no relevant financial conflicts of interest.

Genomic abnormalities can be identified in individual patients with metastatic breast cancer, which can then lead to targeted therapy, investigators reported in the March issue of Lancet Oncology.

In a prospective study of 423 patients who had breast cancer with a metastasis accessible for biopsy, comparative genomic hybridization array was feasible in 283 patients and Sanger sequencing was feasible in 297 patients. A targetable genomic alteration was found in 195 patients (46%), most often PIK3CA mutation (25%), CCND1 amplification (18%), and FGFR1 amplification (12%), reported Dr. Fabrice André of Institut Gustave Roussy, Villejuif, France, and his associates.

The primary endpoint – the ability to offer targeted therapy based on genomic sequencing – was achieved for 55 patients (13%). Of the 43 patients who ultimately received targeted therapy as a result of the genomic analyses, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Grade 3 or higher adverse events related to biopsy were reported in four patients (Lancet Oncol. 2014;15:267-74).

The response rate was "disappointing," but the patient population had been heavily pretreated, the researchers noted.

The result "justifies the development of multiple strategies to improve efficacy of screening" for targeted therapy, the investigators said. They recommended improving algorithms for analyzing genomic data, using highly bioactive agents for targeted therapy, and combining therapies to delay drug resistance.

The study was sponsored by the French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, and Operation Parrains Chercheurs. The authors reported no relevant financial conflicts of interest.

Genomic abnormalities can be identified in individual patients with metastatic breast cancer, which can then lead to targeted therapy, investigators reported in the March issue of Lancet Oncology.

In a prospective study of 423 patients who had breast cancer with a metastasis accessible for biopsy, comparative genomic hybridization array was feasible in 283 patients and Sanger sequencing was feasible in 297 patients. A targetable genomic alteration was found in 195 patients (46%), most often PIK3CA mutation (25%), CCND1 amplification (18%), and FGFR1 amplification (12%), reported Dr. Fabrice André of Institut Gustave Roussy, Villejuif, France, and his associates.

The primary endpoint – the ability to offer targeted therapy based on genomic sequencing – was achieved for 55 patients (13%). Of the 43 patients who ultimately received targeted therapy as a result of the genomic analyses, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks. Grade 3 or higher adverse events related to biopsy were reported in four patients (Lancet Oncol. 2014;15:267-74).

The response rate was "disappointing," but the patient population had been heavily pretreated, the researchers noted.

The result "justifies the development of multiple strategies to improve efficacy of screening" for targeted therapy, the investigators said. They recommended improving algorithms for analyzing genomic data, using highly bioactive agents for targeted therapy, and combining therapies to delay drug resistance.

The study was sponsored by the French National Cancer Institute, Breast Cancer Research Foundation, Odyssea, and Operation Parrains Chercheurs. The authors reported no relevant financial conflicts of interest.

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

tor@frontlinemedcom.com

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

tor@frontlinemedcom.com

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

tor@frontlinemedcom.com

Vaginal mesh surgery had a significantly lower failure rate than did sacrospinous vaginal colpopexy in women with vaginal vault prolapse and levator ani avulsion, investigators reported online March 11 in Ultrasound in Obstetrics & Gynecology.

At 1-year follow-up, 3% of patients treated with mesh had anatomic failure based on clinical and ultrasound evaluation, compared with 62%-65% of patients who underwent unilateral vaginal sacrospinous colpopexy with native tissue vaginal repair, reported Dr. Kamil Svabik and his associates at General University Hospital and the Charles University in Prague.

Vaginal mesh has been linked to adverse effects, so the researchers enrolled patients with post hysterectomy vaginal vault prolapse who also had levator ani avulsion only. "We considered it potentially unethical to offer mesh to all patients with post hysterectomy prolapse due to concerns about mesh complications, and since there is some evidence that reduction in recurrence due to mesh may be limited largely to patients with levator avulsion," they said (Ultrasound Obstet. Gynecol. 2014 March 11 [doi:10.1002/uog.13305]).

Among 70 women with ultrasound-diagnosed avulsions, 36 were randomized to the vaginal mesh procedure and 34 underwent sacrospinous fixation. At 1-year follow-up, there was one anatomic failure in the mesh group, while 22 (65%) patients in the sacrospinous fixation group had prolapses to the hymen or beyond, and 21 (63%) met ultrasound criteria for prolapse. The groups did not differ significantly in terms of incontinence, sexual function, or prolapse symptoms, which the researchers said might be because of the lack of power. No serious adverse effects were reported for either group.

The Gynecare Prolift mesh used in the study has been taken off the market, the investigators said, adding that other type-I polypropylene meshes might achieve similar results. They planned to assess long-term outcomes and complications.

The study was supported by the Grant Agency of the Ministry of Health of the Czech Republic and by Charles University in Prague. The authors disclosed no conflicts of interest except Dr. Martan, who reported having consulted for Bard, Gynecare, and AMS.

obnews@frontlinemedcom.com

Vaginal mesh surgery had a significantly lower failure rate than did sacrospinous vaginal colpopexy in women with vaginal vault prolapse and levator ani avulsion, investigators reported online March 11 in Ultrasound in Obstetrics & Gynecology.

At 1-year follow-up, 3% of patients treated with mesh had anatomic failure based on clinical and ultrasound evaluation, compared with 62%-65% of patients who underwent unilateral vaginal sacrospinous colpopexy with native tissue vaginal repair, reported Dr. Kamil Svabik and his associates at General University Hospital and the Charles University in Prague.

Vaginal mesh has been linked to adverse effects, so the researchers enrolled patients with post hysterectomy vaginal vault prolapse who also had levator ani avulsion only. "We considered it potentially unethical to offer mesh to all patients with post hysterectomy prolapse due to concerns about mesh complications, and since there is some evidence that reduction in recurrence due to mesh may be limited largely to patients with levator avulsion," they said (Ultrasound Obstet. Gynecol. 2014 March 11 [doi:10.1002/uog.13305]).

Among 70 women with ultrasound-diagnosed avulsions, 36 were randomized to the vaginal mesh procedure and 34 underwent sacrospinous fixation. At 1-year follow-up, there was one anatomic failure in the mesh group, while 22 (65%) patients in the sacrospinous fixation group had prolapses to the hymen or beyond, and 21 (63%) met ultrasound criteria for prolapse. The groups did not differ significantly in terms of incontinence, sexual function, or prolapse symptoms, which the researchers said might be because of the lack of power. No serious adverse effects were reported for either group.

The Gynecare Prolift mesh used in the study has been taken off the market, the investigators said, adding that other type-I polypropylene meshes might achieve similar results. They planned to assess long-term outcomes and complications.

The study was supported by the Grant Agency of the Ministry of Health of the Czech Republic and by Charles University in Prague. The authors disclosed no conflicts of interest except Dr. Martan, who reported having consulted for Bard, Gynecare, and AMS.

obnews@frontlinemedcom.com

Vaginal mesh surgery had a significantly lower failure rate than did sacrospinous vaginal colpopexy in women with vaginal vault prolapse and levator ani avulsion, investigators reported online March 11 in Ultrasound in Obstetrics & Gynecology.

At 1-year follow-up, 3% of patients treated with mesh had anatomic failure based on clinical and ultrasound evaluation, compared with 62%-65% of patients who underwent unilateral vaginal sacrospinous colpopexy with native tissue vaginal repair, reported Dr. Kamil Svabik and his associates at General University Hospital and the Charles University in Prague.

Vaginal mesh has been linked to adverse effects, so the researchers enrolled patients with post hysterectomy vaginal vault prolapse who also had levator ani avulsion only. "We considered it potentially unethical to offer mesh to all patients with post hysterectomy prolapse due to concerns about mesh complications, and since there is some evidence that reduction in recurrence due to mesh may be limited largely to patients with levator avulsion," they said (Ultrasound Obstet. Gynecol. 2014 March 11 [doi:10.1002/uog.13305]).

Among 70 women with ultrasound-diagnosed avulsions, 36 were randomized to the vaginal mesh procedure and 34 underwent sacrospinous fixation. At 1-year follow-up, there was one anatomic failure in the mesh group, while 22 (65%) patients in the sacrospinous fixation group had prolapses to the hymen or beyond, and 21 (63%) met ultrasound criteria for prolapse. The groups did not differ significantly in terms of incontinence, sexual function, or prolapse symptoms, which the researchers said might be because of the lack of power. No serious adverse effects were reported for either group.

The Gynecare Prolift mesh used in the study has been taken off the market, the investigators said, adding that other type-I polypropylene meshes might achieve similar results. They planned to assess long-term outcomes and complications.

The study was supported by the Grant Agency of the Ministry of Health of the Czech Republic and by Charles University in Prague. The authors disclosed no conflicts of interest except Dr. Martan, who reported having consulted for Bard, Gynecare, and AMS.

obnews@frontlinemedcom.com

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

Maintenance percutaneous tibial nerve stimulation in patients with multiple sclerosis led to sustained improvements in medically refractory lower urinary tract symptoms in a prospective, multicenter open-label trial.

All initial responders continued to respond after an average of 2 years of maintenance therapy, reported Dr. Claudio Gobbi of the Neurocentre of Southern Switzerland, Lugano, and his associates.

The prospective, multicenter open-label study recruited patients with multiple sclerosis who had lower urinary tract symptoms that had not responded to medical therapy. Symptom criteria included overactive bladder, incomplete voiding, hesitancy, poor or slow flow, prolonged and interrupted flow, and straining to void (J. Urol. 2014;191:697-702).

A total of 83 patients (mean age, 49 years; 62 women) completed 12 initial weekly sessions of percutaneous tibial nerve stimulation (PTNS). In all, 74 (89%) reported at least 50% improvement in lower urinary tract symptoms on the Patient Perception of Bladder Condition questionnaire.

These responders then underwent 30-minute PTNS maintenance sessions every 2, 3, or 4 weeks as needed. Most patients (60%) required treatment every 2 weeks, the researchers said.

After the 12 weekly PTNS treatments, most responders reported their bladder symptoms as moderately improved (based on a global response assessment), and mean treatment satisfaction was 70% (based on a visual analog scale). At 24 months’ follow-up, most patients described their symptoms as markedly improved, and mean treatment satisfaction was 82% (P less than .05).

The investigators also reported significant improvements over a 24-month period in measures of voiding and bladder diary parameters (including frequency of daytime urination, nocturia, and voided volume). Patients reported no relevant adverse effects of treatment.

Dr. Gobbi and his associates noted several caveats to their findings. The study probably lacked sufficient power to detect differences between subgroups, they said. The investigators also did not collect data on drinking habits or lifestyle modifications, each of which could have independently affected treatment outcomes. And the study included only patients who responded to and completed the initial treatment, which created a selection bias for patients willing to adhere to maintenance PTNS.

"Although the efficacy of PTNS was sustained for 2 years, the progressive neurologic course of MS with deteriorating bladder function may affect longer positive treatment outcomes," they added.

One author disclosed having financial interests or other relationships with Medtronic, Allergan, and Astellas. Dr. Gobbi and his other coauthors reported no conflicts of interest.

Early response to dasatinib predicted better long-term survival in adults with chronic phase chronic myeloid leukemia who had failed imatinib treatment, investigators reported online Feb. 25 in Blood.

Dr. Neil P. Shah of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and his associates followed 670 patients with chronic phase chronic myeloid leukemia from a phase III randomized dose-optimization study of dasatinib. Patients were resistant to or could not tolerate imatinib.

Patients received dasatinib at 100 mg daily, 140 mg daily, 50 mg b.i.d., or 70 mg b.i.d (Blood 2014 [doi: 10.1182/blood-2013-10-532341]).

At 6 years, the 100-mg group had an overall survival of 71% and a progression-free survival of 49.3%, with the lowest rates of discontinuation because of toxicity.

A BCR-ABL transcript level of 10% or less at 3 months was a "particularly strong predictor" of survival, researchers reported.

Patients who achieved this level had 6-year progression-free survival rates of 58% to 68%, compared with 26% for other patients.

A major cytogenetic response at 3 and 6 months also predicted better progression-free and overall survival.

Dr. Shah and nine of his associates reported receiving support from or serving as consultants to Bristol-Myers Squibb, who funded the study, and three other associates reported being employees of Bristol-Myers Squibb.

Early response to dasatinib predicted better long-term survival in adults with chronic phase chronic myeloid leukemia who had failed imatinib treatment, investigators reported online Feb. 25 in Blood.

Dr. Neil P. Shah of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and his associates followed 670 patients with chronic phase chronic myeloid leukemia from a phase III randomized dose-optimization study of dasatinib. Patients were resistant to or could not tolerate imatinib.

Patients received dasatinib at 100 mg daily, 140 mg daily, 50 mg b.i.d., or 70 mg b.i.d (Blood 2014 [doi: 10.1182/blood-2013-10-532341]).

At 6 years, the 100-mg group had an overall survival of 71% and a progression-free survival of 49.3%, with the lowest rates of discontinuation because of toxicity.

A BCR-ABL transcript level of 10% or less at 3 months was a "particularly strong predictor" of survival, researchers reported.

Patients who achieved this level had 6-year progression-free survival rates of 58% to 68%, compared with 26% for other patients.

A major cytogenetic response at 3 and 6 months also predicted better progression-free and overall survival.

Dr. Shah and nine of his associates reported receiving support from or serving as consultants to Bristol-Myers Squibb, who funded the study, and three other associates reported being employees of Bristol-Myers Squibb.

Early response to dasatinib predicted better long-term survival in adults with chronic phase chronic myeloid leukemia who had failed imatinib treatment, investigators reported online Feb. 25 in Blood.

Dr. Neil P. Shah of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and his associates followed 670 patients with chronic phase chronic myeloid leukemia from a phase III randomized dose-optimization study of dasatinib. Patients were resistant to or could not tolerate imatinib.

Patients received dasatinib at 100 mg daily, 140 mg daily, 50 mg b.i.d., or 70 mg b.i.d (Blood 2014 [doi: 10.1182/blood-2013-10-532341]).

At 6 years, the 100-mg group had an overall survival of 71% and a progression-free survival of 49.3%, with the lowest rates of discontinuation because of toxicity.

A BCR-ABL transcript level of 10% or less at 3 months was a "particularly strong predictor" of survival, researchers reported.

Patients who achieved this level had 6-year progression-free survival rates of 58% to 68%, compared with 26% for other patients.

A major cytogenetic response at 3 and 6 months also predicted better progression-free and overall survival.

Dr. Shah and nine of his associates reported receiving support from or serving as consultants to Bristol-Myers Squibb, who funded the study, and three other associates reported being employees of Bristol-Myers Squibb.

Hormone therapy was associated with improved overall survival in women with non–small-cell lung carcinoma, reported investigators in the March issue of the Journal of Thoracic Oncology.

Long-term hormone use and combinations of estrogen and progesterone predicted the most significant survival benefit, reported Dr. Ann G. Schwartz of the Karmanos Cancer Institute and Wayne State University, both in Detroit, and her associates.

Women with lung cancer usually live longer than do men with the disease. But few prior studies have examined associations between reproductive factors, hormone therapy, and lung cancer outcomes, and results have been inconsistent, investigators said (J. Thorac. Oncol. 2014;9:355-61).

Researchers interviewed 485 women who were diagnosed with non–small-cell lung carcinoma between 2001 and 2005, about their reproductive histories and type, dose, and duration of hormone therapy.

Only hormone therapy predicted overall survival (hazard ratio, 0.69; 95% confidence interval, 0.54-0.89) after accounting for stage at diagnosis, surgery, radiation, education level, cigarette smoke exposure, age, and race, the investigators reported.

Women who received hormone therapy prior to lung cancer diagnosis survived a median of 80 months, compared with 37.5 months for women who did not.

The survival benefit was most significant when hormone therapy lasted 11 years or longer, particularly for combinations of estrogen and progesterone (HR, 0.50; 95% CI, 0.30-0.83). Taking estrogen alone for less than 11 years had no significant effect.

Because patients had to be healthy enough to participate in the survey, results might not apply to all women with non–small-cell lung cancer, Dr. Schwartz and associates noted.

"These findings suggest a complex relationship between exposure to exogenous hormones and lung cancer outcomes," added the researchers. They recommended research to explore the biological reasons for their findings.

This study was supported by the National Institutes of Health. The authors disclosed no relevant financial conflicts of interest.

Hormone therapy was associated with improved overall survival in women with non–small-cell lung carcinoma, reported investigators in the March issue of the Journal of Thoracic Oncology.

Long-term hormone use and combinations of estrogen and progesterone predicted the most significant survival benefit, reported Dr. Ann G. Schwartz of the Karmanos Cancer Institute and Wayne State University, both in Detroit, and her associates.

Women with lung cancer usually live longer than do men with the disease. But few prior studies have examined associations between reproductive factors, hormone therapy, and lung cancer outcomes, and results have been inconsistent, investigators said (J. Thorac. Oncol. 2014;9:355-61).

Researchers interviewed 485 women who were diagnosed with non–small-cell lung carcinoma between 2001 and 2005, about their reproductive histories and type, dose, and duration of hormone therapy.

Only hormone therapy predicted overall survival (hazard ratio, 0.69; 95% confidence interval, 0.54-0.89) after accounting for stage at diagnosis, surgery, radiation, education level, cigarette smoke exposure, age, and race, the investigators reported.

Women who received hormone therapy prior to lung cancer diagnosis survived a median of 80 months, compared with 37.5 months for women who did not.

The survival benefit was most significant when hormone therapy lasted 11 years or longer, particularly for combinations of estrogen and progesterone (HR, 0.50; 95% CI, 0.30-0.83). Taking estrogen alone for less than 11 years had no significant effect.

Because patients had to be healthy enough to participate in the survey, results might not apply to all women with non–small-cell lung cancer, Dr. Schwartz and associates noted.

"These findings suggest a complex relationship between exposure to exogenous hormones and lung cancer outcomes," added the researchers. They recommended research to explore the biological reasons for their findings.

This study was supported by the National Institutes of Health. The authors disclosed no relevant financial conflicts of interest.

Hormone therapy was associated with improved overall survival in women with non–small-cell lung carcinoma, reported investigators in the March issue of the Journal of Thoracic Oncology.

Long-term hormone use and combinations of estrogen and progesterone predicted the most significant survival benefit, reported Dr. Ann G. Schwartz of the Karmanos Cancer Institute and Wayne State University, both in Detroit, and her associates.

Women with lung cancer usually live longer than do men with the disease. But few prior studies have examined associations between reproductive factors, hormone therapy, and lung cancer outcomes, and results have been inconsistent, investigators said (J. Thorac. Oncol. 2014;9:355-61).

Researchers interviewed 485 women who were diagnosed with non–small-cell lung carcinoma between 2001 and 2005, about their reproductive histories and type, dose, and duration of hormone therapy.

Only hormone therapy predicted overall survival (hazard ratio, 0.69; 95% confidence interval, 0.54-0.89) after accounting for stage at diagnosis, surgery, radiation, education level, cigarette smoke exposure, age, and race, the investigators reported.

Women who received hormone therapy prior to lung cancer diagnosis survived a median of 80 months, compared with 37.5 months for women who did not.

The survival benefit was most significant when hormone therapy lasted 11 years or longer, particularly for combinations of estrogen and progesterone (HR, 0.50; 95% CI, 0.30-0.83). Taking estrogen alone for less than 11 years had no significant effect.

Because patients had to be healthy enough to participate in the survey, results might not apply to all women with non–small-cell lung cancer, Dr. Schwartz and associates noted.

"These findings suggest a complex relationship between exposure to exogenous hormones and lung cancer outcomes," added the researchers. They recommended research to explore the biological reasons for their findings.

This study was supported by the National Institutes of Health. The authors disclosed no relevant financial conflicts of interest.