Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of medication adherence.

PURPOSE: The aim of this study was to determine the prevalence of adherence to adjuvant hormonal therapy (AHT) and to identify risk factors for medication non-adherence in clinical practice in patients with early-stage hormone receptor (HR)-positive breast cancer (BC) previously treated with chemotherapy. METHODS: We carried out a cross-sectional, observational, prospective, and multicenter survey based on a structured self-report postal questionnaire (35 items investigating six areas). A sample of 474 patients was drawn from 676 patients potentially eligible. The structured and validated Morisky Medication Adherence Scale-4 items was used for measuring medication adherence. An analysis of risk factors for non-adherence to AHT was performed using a two-step approach: univariate, then multivariate analysis. RESULTS: A total of 280 patients out of the 428 analyzed patients participated in the survey, yielding a response rate of 65.4% [60.9-69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1-74.0], corresponding to a high level of adherence. Three risk factors for non-adherence to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003), age less than 65 years (p-value = 0.008), and patient management in a university hospital setting (p-value = 0.014). CONCLUSIONS: Non-adherence is a common, complex, and multidimensional healthcare problem. This better understanding and knowledge of risk factors will allow healthcare providers (such as oncologists, general practitioners, pharmacists) to more easily identify patients at risk for non-adherence and help them provide appropriate information about AHT and its management, thus improving medication adherence in their patients.

[Prevalence and management of pain in patients with metastatic cancer in Franche-Comté]. / Prévalence et prise en charge de la douleur chez les patients présentant un cancer métastatique en Franche-Comté.

INTRODUCTION: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain. METHODS: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included. RESULTS: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life. CONCLUSION: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate.

Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials.

[Efficacy, safety and cost of eribulin in patients with metastatic breast cancer]. / Efficacité, tolérance et coût de l'éribuline chez des patientes présentant un cancer du sein métastatique.

Eribulin gained its approval in March 2011 for the treatment of patients with locally advanced or metastatic breast cancer (MBC) whose disease has progressed despite anthracycline and taxane-containing regimens. This study retrospectively assessed the efficacy, safety and cost of this treatment for all patients with MBC treated by eribulin in Franche-Comté. Ninety-four patients received eribulin between July 2006 and October 2013. The median age was 62 years (35-83). Median overall survival was 10.3 months [95% CI: 7.6 to 17.9]. Median progression-free-survival was 3.8 months [95% CI: 2.9 to 5.0]. Clinical benefit was obtained in 55% evaluable patients [95% CI: 43.1 to 66.9] by RECIST criteria. Most common grade 3-4 adverse events (AEs) were neutropenia (38%), asthenia (10%) and peripheral neuropathy (7%). Median cost of the treatment was 9767 € per patient (6344-17,517). This analysis found similar results to the EMBRACE study despite less selected population. A medico-economic evaluation cost-utility type would assess the effectiveness of this strategy compared to standard treatments.

In the era of genomics, should tumor size be reconsidered as a criterion for neoadjuvant chemotherapy?

BACKGROUND: The Oncotype DX recurrence score (RS) assay has been validated for prediction of 10-year risk of distant recurrence and likelihood of benefit from chemotherapy in patients with estrogen receptor (ER)-positive, HER2-negative early breast cancer. Patients with high RS tumors have substantial benefit, and patients with low RS tumors have minimal if any benefit from chemotherapy. Tumor size is used as a key parameter when selecting patients for neoadjuvant chemotherapy. The aim of this study was to assess the distribution of RS in patients selected for neoadjuvant chemotherapy primarily according to tumor size. PATIENTS AND METHODS: Patients with ER-positive and HER2-negative tumors that were node-negative or had no more than 1 positive node from three trials were included in this study. Oncotype DX was performed at Genomic Health, Inc., blinded to the clinical data. Descriptive statistics were calculated for distribution of RS for all cases. RESULTS: Of 277 patients, 96 met eligibility criteria, and 81 had sufficient material for analysis. Median tumor size was 40 mm (interquartile range [IQR], 30-50 mm). Grade I, II, and III were observed in 13, 49, and 17 cases, respectively. There was a wide distribution of RS with a median of 21.4 (IQR, 16.05-26.75). In total, 23 (28.3%) had high, 28 (34.6%) intermediate, and 30 (37%) low RS results. CONCLUSION: The RS may provide relevant information for neoadjuvant treatment decisions in select patients both in clinical practice and in studies. Inclusion of low RS disease patients in neoadjuvant trials will likely only dilute the ability to look at treatment effects.

Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study.

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m2 intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9-4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06-12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy.

[Economic assessment of the routine use of Oncotype DX® assay for early breast cancer in Franche-Comte region]. / Évaluation économique de l'utilisation en routine du test Oncotype DX® dans la prise en charge des cancers du sein en Franche-Comté.

Oncotype DX® has been validated as quantifying the likelihood of distant recurrence at 10 years and overall chemotherapy benefit in patients with estrogen-receptor-positive and HER-2-negative early breast cancer. In 2012, this genomic signature was routinely available for patients in Franche-Comté, France. Patients eligible for Oncotype DX(®) testing had a ER-positive, HER-2-négative early breast cancer with a nodal involvement limited to 0 or 1 positive-node without extracapsular spread; an adjuvant chemotherapy was indicated based on usual prognostic factors. The aim was to assess the economic impact of Oncotype DX(®) testing in a French region. A cost-minimisation analysis from the French Public Healthcare System perspective was performed. The availability of Oncotype DX(®) in Franche-Comté, France, and its use in clinical routine allowed a decrease of 73 % of adjuvant chemotherapy without increase of the cost of the patients' management and with a potential reduction of the cost for the French Public Healthcare System. This strategy was successful and may allow the reimbursement of this test in France for patients with early breast cancer.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma.

INTRODUCTION: The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. PATIENTS AND METHODS: All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. RESULTS: For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13-22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22-0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31-0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22-0.82], P=0.002). Median OS was 21 months [14-29 months] for patients who received at least one targeted therapy compared with 12 months [7-15 months] for patients who were treated only by immunotherapy agents (P=0.003). CONCLUSION: Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications.

First-line trastuzumab plus taxane-based chemotherapy for metastatic breast cancer: cost-minimization analysis.

AIM: To carry out a cost-minimization analysis including a comparison of the costs arising from first-line treatment by trastuzumab plus docetaxel versus trastuzumab plus paclitaxel in patients with metastatic breast cancer. METHODS: All consecutive patients with human epidermal growth receptor 2-postive metastatic breast cancer who were treated at Besançon University Hospital and Saint Vincent private hospital between 2001 and 2010 by first-line therapy containing trastuzumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization, and healthcare travel. RESULTS: Progression-free survival difference between the two treatments was not significant (p = 0.65). First-line treatment by trastuzumab plus taxane was estimated at approximately €68,000 (p = 0.74). The drug costs represented around 70-75% of the total cost, mainly related to the use of trastuzumab. CONCLUSION: Our economic analysis shows that although the costs of the two trastuzumab plus taxane regimens are similar, they may contribute to the on-going debate about the availability and use of innovative chemotherapy drugs, in particular in human epidermal growth factor receptor 2-positive metastatic breast cancer with new therapies such as trastuzumab-DM1 and pertuzumab.

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: impact of institutions.

PURPOSE: Trastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given. PATIENTS & METHODS: All patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS). RESULTS: Among 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2-89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64-0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59-0.95; p = 0.02). CONCLUSION: Exposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.

Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis.

BACKGROUND: The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. METHODS: Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization. RESULTS: From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p = 4 × 10(-3)), PR in 29% of cancers (p < 4 × 10(-4)), and HER2 in 4% of lesions (p = .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed. CONCLUSIONS: This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting.

Safety and efficacy of cabazitaxel in the docetaxel-treated patients with hormone-refractory prostate cancer.

Prostate cancer (PC) is one of the most common cancers and is a leading cause of death. Its initial growth is dependent on androgens; most patients show an initial response to hormonal therapy but will experience disease progression when PC becomes resistant to castration. In 2004, two key randomized controlled trials demonstrated a benefit for docetaxel-based regimens in the treatment of men with castration-resistant prostate cancer (CRPC). Cabazitaxel (XRP6258, TXD258, and RPR116258A), a tubulin-binding taxane drug as potent as docetaxel in cell lines, was the first treatment able to prolong survival for metastatic CRPC in the post-docetaxel setting. This review describes pharmacologic parameters of this agent followed by a review of clinical trials involving cabazitaxel. Other available treatments and the place of cabazitaxel in metastatic CRPC setting are discussed.

Responsiveness of EORTC QLQ-C30, QLQ-CR38 and FACT-C quality of life questionnaires in patients with colorectal cancer.

BACKGROUND: The aim of this study was to compare the responsiveness of the European Organization for Research and Treatment (EORTC) quality of life questionnaires (QLQ-C30, QLQ-CR38) and the Functional Assessment of Cancer Therapy-colorectal version 4 questionnaire (FACT-C). METHOD: This prospective study included 127 patients with colorectal cancer: 71 undergoing chemotherapy and 56 radiation therapy. Responsiveness statistics included the Standardized Response Mean (SRM) and the Effect Size (ES). The patient's overall assessment of his/her change in state of health status was the reference criterion to evaluate the responsiveness of the QoL questionnaires. RESULTS: 34 patients perceived their health as stable and 17 as improved between the first and the fourth courses of chemotherapy. 21 patients perceived their health as stable and 22 as improved between before and the last week of radiotherapy.The responsiveness of the 3 questionnaires differed according to treatments. The EORTC QLQ-C30 questionnaire was more responsive in patients receiving chemotherapy, particulary functional scales (SRM > 0.55). The QLQ-CR38 and the FACT-C questionnaires provided little clinically relevant information during chemotherapy or radiotherapy. CONCLUSION: The EORTC QLQ-C30 questionnaire appears to be more responsive in patients receiving chemotherapy.

[Influence of the delay between conservative surgery and radiation therapy on local relapse in node-positive breast tumor]. / Rôle du délai chirurgie conservatrice-radiothérapie sur les rechutes locales du cancer du sein avec envahissement ganglionnaire.

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

Influence of the time between surgery and radiotherapy on local recurrence in patients with lymph node-positive, early-stage, invasive breast carcinoma undergoing breast-conserving surgery: results of the French Adjuvant Study Group.

BACKGROUND: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC. METHODS: Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50 mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of patients. RESULTS: After a median follow-up of 102 months, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02). Patients who received hormone therapy were less likely to develop LR (P = 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors. CONCLUSIONS: In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk.

Long-term cardiac follow-up in relapse-free patients after six courses of fluorouracil, epirubicin, and cyclophosphamide, with either 50 or 100 mg of epirubicin, as adjuvant therapy for node-positive breast cancer: French adjuvant study group.

PURPOSE To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 50) or the same regimen with epirubicin 100 mg/m(2) (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group-05 trial. PATIENTS AND METHODS One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. CONCLUSION After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.