Secondary analyses of the randomized phase III Stop&Go study: efficacy of second-line intermittent versus continuous chemotherapy in HER2-negative advanced breast cancer

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule. Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous). Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82–1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98–1.66) for intermittent versus continuous second

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p

Single-nucleotide polymorphisms in the genes of CES2, CDA and enzymatic activity of CDA for prediction of the efficacy of capecitabine-containing chemotherapy in patients with metastatic breast cancer

We examined whether genetic polymorphisms (SNPs) in the capecitabine activation pathway and CDA enzymatic activity were associated with prognosis, benefit from capecitabine-containing treatment or capecitabine-related toxicities. The study population comprised 188 metastatic breast cancer patients of the ATX trial (EudraCT 2006-006058-83) randomized for first-line paclitaxel and bevacizumab with (ATX) or without capecitabine (AT). Cumulative capecitabine dose until grade ≥2 hand-foot syndrome or until first dose reduction were toxicity endpoints. We genotyped CDA c.-451C. >. T (rs532545), CDA c.-33delC (rs3215400) and CES2 c.-806C. >. G (rs11075646). CDA activity in baseline serum was measured with a spectrophotometric assay and values were analyzed using a median cut-off or as continuous variable. CDA c.-33delC was prognostic for overall survival (OS) independent of hormone receptor status. For the predictive analysis, progression-free survival benefit from ATX over AT was observed in patients with a CDA c.-33del/del or del/insC genotype, a CDA c.-451CC or CT genotype, and a CES2 c.-806CC genotype compared with their counterparts. There was a higher response rate for ATX over AT in patients with a CDA c.-451CT or TT genotype. Patients with high CDA enzymatic activity had more benefit from capecitabine, while this was marginally observed in the CDA low group. Toxicity endpoints were not associated with any candidate markers. In conclusion, CDA c.-33delC was associated with OS. Since particular SNPs in CDA and CES2 were associated with benefit from the addition of capecitabine to AT, their predictive value should be explored in a higher number of patients