Platinum-containing regimens for metastatic breast cancer.

BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. Most of these studies were conducted prior to the 'intrinsic subtype' era, and did not specifically focus on metastatic triple-negative breast cancers (mTNBCs). OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. SEARCH METHODS: For this review update, we searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov on 28 May 2015. We identified further potentially relevant studies from handsearching references of previous trials, systematic reviews, and meta-analyses. Prior to this review update, the most recent search for studies was conducted in May 2003 for the original 2004 review. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: At least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. Hazard ratios (HRs) were derived for time-to-event outcomes, where possible, and fixed-effect models were used for meta-analyses. Objective tumour response rates (OTRRs) and toxicities were analysed as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. Quality of life data were extracted where available. GRADE was used to rate the quality of evidence for survival and tumour response outcomes at the level of subgroups selected and unselected for mTNBC, and for toxicity outcomes based on combining data from selected and unselected populations. MAIN RESULTS: This update includes 15 new eligible treatment-comparisons from 12 studies. In total, 28 treatment-comparisons, involving 4418 women, from 24 studies are now included in one or more meta-analyses. Of the 28 treatment-comparisons, 19 and 16 had published or provided extractable time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively. All 28 treatment-comparisons provided OTRR data that could be included in meta-analyses. Most women recruited to the studies were not selected on the basis of mTNBC status.In a subgroup of three treatment-comparisons assessing women with mTNBC, platinum-containing regimens may have provided a survival benefit (HR 0.75, 95% CI 0.57 to 1.00; low-quality evidence). In women unselected for intrinsic subtypes such as mTNBC, there was little or no effect on survival (HR 1.01, 95% CI 0.92 to 1.12; high-quality evidence). This effect was similar to the combined analysis of survival data for both populations (HR 0.98, 95% CI 0.89 to 1.07; I2 =39%, 1868 deaths, 2922 women; 19 trials). The difference in treatment effects between mTNBC women compared with unselected women was of borderline statistical significance (P = 0.05).Data from three treatment-comparisons with mTNBC participants showed that platinum regimens may improve PFS/TTP (HR 0.59, 95% CI 0.49 to 0.72; low-quality evidence). Thirteen treatment-comparisons of unselected metastatic participants showed that there was probably a small PFS/TTP benefit for platinum recipients, although the confidence interval included no difference (HR 0.92, 95% CI 0.84 to 1.01; moderate-quality evidence). Combined analysis of data from an estimated 1772 women who progressed or died out of 2136 women selected or unselected for mTNBC indicated that platinum-containing regimens improved PFS/TTP (HR 0.85, 95% CI 0.78 to 0.93). There was marked evidence of heterogeneity (P = 0.0004; I2 = 63%). The larger treatment benefit in mTNBC women compared with unselected women was statistically significant (P < 0.0001).There was low-quality evidence of better tumour response in both subgroups of women with mTNBC and unselected women (RR 1.33, 95% CI 1.13 to 1.56; RR 1.11, 95% CI 1.04 to 1.19, respectively). Combined analysis of both populations was closer to the effect in unselected women (RR 1.15, 95% CI 1.08 to 1.22; 4130 women). There was considerable evidence of heterogeneity (P < 0.0001; I2 = 64%), which may reflect between-study differences and general difficulties in assessing response, as well as the varying potencies of the comparators.Compared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were probably higher among women receiving cisplatin- (RR 2.65, 95% CI 2.10 to 3.34; 1731 women; moderate-quality evidence) but the effect from carboplatin-containing regimens was less certain (RR 0.77, 95% CI 0.47 to 1.26; 1441 women; moderate-quality evidence); rates of grade 3 and 4 anaemia were higher among women receiving cisplatin- (RR 3.72, 95% CI 2.36 to 5.88; 1644 women; high-quality evidence) and carboplatin-containing regimens (RR 1.72, 95% CI 1.10 to 2.70; 1441 women; high-quality evidence); rates of grade 3 and 4 hair loss (RR 1.41, 95% CI 1.26 to 1.58; 1452 women; high-quality evidence) and leukopenia (RR 1.38, 95% CI 1.21 to 1.57; 3176 women; moderate-quality evidence) were higher among women receiving platinum-containing regimens (regardless of platinum agent). AUTHORS' CONCLUSIONS: In women with metastatic breast cancer who do not have triple-negative disease, there is high-quality evidence of little or no survival benefit and excess toxicity from platinum-based regimens. There is preliminary low-quality evidence of a moderate survival benefit from platinum-based regimens for women with mTNBC. Further randomised trials of platinum-based regimens in this subpopulation of women with metastatic breast cancer are required.

Single agent versus combination chemotherapy for metastatic breast cancer.

BACKGROUND: Combination chemotherapy regimens are frequently favoured over single agents for the treatment of metastatic breast cancer, in an attempt to achieve superior tumour response rates. It is not known however whether giving more intensive chemotherapy regimens results in better health outcomes, when both survival and toxicity are considered, and whether better response rates and rates of progression free survival actually translate to better overall survival. OBJECTIVES: To compare single agent with combination chemotherapy for the treatment of metastatic breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register November 2008. Handsearching of recent conference proceedings was also undertaken. SELECTION CRITERIA: Randomised trials of single agent chemotherapy compared to combination therapy in metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for eligibility and quality, and extracted data. Hazard ratios were derived for reported time-to-event outcomes.Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present. MAIN RESULTS: Forty three eligible trials (48 comparisons) were identified. These included 9742 women, 55% of whom were receiving first-line treatment for metastatic disease. For overall survival there was a statistically significant difference in favour of the combination regimens with no heterogeneity (HR 0.88, 95% CI 0.83-0.93, p<0.00001). Results were very similar when trials of first-line treatment were analysed, and for analyses where the single agent was also included in the combination regimen. Combination regimens showed a statistically significant advantage for survival over single agent taxane (HR 0.82; 95% CI 0.75-0.89, p<0.00001), but not anthracycline (HR 0.94.86-1.02, p=0.15).Combination regimens were also associated with significantly better time to progression (HR 0.78, 95% CI 0.74 - 0.82, p<0.00001) and response (RR 1.29, 95% CI 1.14 -1.45, p<0.0001) although heterogeneity was statistically significant in both instances and probably due to clinical diversity of the participants and interventions.Women receiving combination regimens experienced a statistically significant detrimental effect on white cell count, increased alopecia and nausea and vomiting. AUTHORS' CONCLUSIONS: Combination chemotherapy regimens show a statistically significant advantage for survival, tumor response and time to progression in women with metastatic breast cancer but they also produce more toxicity. An unresolved question is whether combination regimens are more effective than single agents given sequentially.

Sustaining hope when communicating with terminally ill patients and their families: a systematic review.

The aim of this systematic review was to examine studies that have investigated sustaining hope during prognostic and end-of-life issues discussions with terminally ill patients and their families. A comprehensive search of databases (MEDLINE, EMBASE, CINAHL, PsychINFO, Cochrane Central Register of Controlled Trials) and handsearching, from 1985 to June 2006, identified 27 studies. This review suggests that the issues surrounding hope in this context are complex. Despite the lack of unanimity among researchers regarding the definition of hope, findings suggest that balancing hope with honesty is an important skill for health professionals (HPs). Many patients seem to be able to maintain a sense of hope despite acknowledging the terminal nature of their illness. Patients and caregivers mostly preferred honest and accurate information, provided with empathy and understanding. Many different sources of hope were identified in this context in broad aspects of life, not just the medical situation. HPs need to recognize this spectrum of hope and appreciate that patients may simultaneously hope for 'cure' while acknowledging the terminal nature of their illness. HPs may help patients to cope with their terminal prognosis by exploring and fostering realistic forms of hope that are meaningful for the particular patient and their family.

Truth-telling in discussing prognosis in advanced life-limiting illnesses: a systematic review.

Many health professionals (HPs) express discomfort at having to broach the topic of prognosis, including limited life expectancy, and may withhold information or not disclose prognosis. A systematic review was conducted of 46 studies relating to truth-telling in discussing prognosis with patients with progressive, advanced life-limiting illnesses and their caregivers. Relevant studies meeting the inclusion criteria were identified by searching computerized databases (MEDLINE, EMBASE, CINAHL, PsychINFO and Cochrane Register of Controlled Trials) up to November 2004, with handsearching of studies, as well as inclusion of studies satisfying selection criteria reported in 2005 by the authors. The reference lists of identified studies were hand-searched for further relevant studies. Inclusion criteria were studies of any design evaluating communication of prognostic information that included adult patients with an advanced, life-limiting illness; their caregivers; and qualified HPs. Results showed that although the majority of HPs believed that patients and caregivers should be told the truth about the prognosis, in practice, many either avoid discussing the topic or withhold information. Reasons include perceived lack of training, stress, no time to attend to the patient's emotional needs, fear of a negative impact on the patient, uncertainty about prognostication, requests from family members to withhold information and a feeling of inadequacy or hopelessness regarding the unavailability of further curative treatment. Studies suggest that patients can discuss the topic without it having a negative impact on them. Differences and similarities in findings from different cultures are explored.

Discrepant perceptions about end-of-life communication: a systematic review.

Little research has compared the perceptions of health professionals (HPs), patients, and caregivers about the communication of prognostic information. The objectives of this literature review were to determine 1) patient and caregiver perceptions of levels of information received about prognosis and end-of-life (EoL) issues regarding a life-limiting illness; 2) patient perceptions of and factors related to their understanding and awareness of prognosis; 3) HPs' perceptions of patients' wishes about disclosure of prognosis and factors related to their decision whether to disclose; and 4) concordance between HPs and patients/caregivers regarding the information given by HPs about prognostic and EoL issues. Relevant studies meeting the inclusion criteria were identified by searching computerized databases (MEDLINE, EMBASE, CINAHL, PsychINFO, Cochrane Register of Controlled Trials [Central]) up to November 2004. The reference lists of identified studies were hand searched for further relevant studies. Inclusion criteria were studies of any design evaluating communication of prognostic information that included adult patients with an advanced, life-limiting illness; their caregivers; and qualified HPs. Fifty-one studies were identified. There was a large discrepancy between patients/caregivers and HPs regarding the amount of information they believed had been given. Patients' understanding and awareness of information received conflicted with the HPs' perceptions of patients' understanding and awareness of the information that had been given. HPs tended to underestimate patients' need for information and overestimate patients' understanding and awareness of their prognosis and EoL issues. HPs need to repeatedly check patients' understanding and preferences for information.

A systematic review of prognostic/end-of-life communication with adults in the advanced stages of a life-limiting illness: patient/caregiver preferences for the content, style, and timing of information.

Evidence-based recommendations concerning how to discuss dying, life expectancy, and likely future symptoms with patients with a limited life expectancy and their families are lacking. The aim of this systematic review was to review studies regarding prognostic/end-of-life communication with adult patients in the advanced stages of a life-limiting illness and their caregivers. Relevant studies meeting the inclusion criteria were identified by searching computerized databases up to November 2004. One hundred twenty-three studies met the criteria for the full review, and 46 articles reported on patient/caregiver preferences for content, style, and timing of information. The majority of the research was descriptive. Although there were individual differences, patients/caregivers in general had high levels of information need at all stages of the disease process regarding the illness itself, likely future symptoms and their management, and life expectancy and information about clinical treatment options. Patient and caregiver information needs showed a tendency to diverge as the illness progressed, with caregivers needing more and patients wanting less information. Patients and caregivers preferred a trusted health professional who showed empathy and honesty, encouraged questions, and clarified each individual's information needs and level of understanding. In general, most patients/caregivers wanted at least some discussion of these topics at the time of diagnosis of an advanced, progressive, life-limiting illness, or shortly after. However, they wanted to negotiate the content and extent of this information.

An evidence-based specialist breast nurse role in practice: a multicentre implementation study.

The objective of this study was to examine the feasibility, implementation, acceptability and impact of an evidence-based specialist breast care nurse (SBN) model of care in Australia. Primary data were collected from four diverse Australian breast cancer treatment centres over a 12-month period. The design was a multicentre demonstration project. Information about the provision of care and patient needs was collected through prospective logs. Structured interviews were conducted with women who received the SBN intervention (N = 167) and with a control group of women treated prior to the intervention period (N = 133). Health professionals (N = 47) were interviewed about their experience of the SBN. Almost all women had contact with an SBN at five scheduled consultations and 67% of women in the intervention group requested at least one additional consultation with the SBN. Women in the intervention group were more likely to receive hospital fact sheets and to be told about and participate in clinical trials. Ninety-eight per cent of women reported that the availability of an SBN would affect their choice of hospital, with 48% indicating that they would recommend only a hospital with a SBN available. Health professionals reported that SBNs improved continuity of care, information and support for the women, and resulted in more appropriate referrals and use of the time of other members of the team. In conclusion, the SBN model is feasible and acceptable within diverse Australian treatment centres; there is evidence that some aspects of care were improved by the SBN.