Breast cancer treatment for elderly women: a systematic review

Transcription

1 Breast cancer treatment for elderly women: a systematic review Gerlinde Pilkington Rumona Dickson Anna Sanniti Funded by the NCEI and POI

2 Elderly people less likely to receive chemotherapy than younger people with cancer Uncertainties as to whether elderly people can tolerate chemotherapy Elderly people underrepresented in clinical trials Lack of data on outcomes for elderly people treated with chemotherapy Background Funded by the National Cancer Equality Initiative (NCEI) and the Pharmaceutical Oncology Initiative (POI) Six systematic reviews investigating the efficacy and tolerability of chemotherapy to treat elderly people with: Breast cancer Lung cancer Colorectal Cancer Renal cell carcinoma Chronic myeloid leukaemia Non-Hodgkin s lymphoma 1

3 Aims and objectives Aim To systematically review the evidence for the clinical effectiveness and tolerability of chemotherapy regimens used to treat breast cancer in elderly people Objectives summarise the relevant evidence related to clinical effectiveness and tolerability to treatment explore the implications of these findings for practice and service provision in order to disseminate accessible information to clinicians inform future decisions on research priorities through the identification of gaps and weaknesses in the available evidence 2

4 Methods Searching MEDLINE, EMBASE, The Cochrane Library, Web of Knowledge January 2000 to May 2013 Exported to EndNote, duplicates removed Screening Two reviewers screen titles and abstracts independently Potentially relevant studies obtained Selection Two reviewers independently assess studies for inclusion Studies not meeting inclusion criteria excluded Data extraction Data were extracted on study design, population characteristics and outcomes by one reviewer, checked for accuracy by a second RCTs were quality assessed 3

5 Inclusion criteria Patient population Interventions Comparators Older/elderly people (as defined in study) treated for breast cancer Any chemotherapy (all lines of treatment) An alternative chemotherapy Best supportive care Outcomes Efficacy outcomes: Overall survival Response rates Time to event measures Tolerability outcomes: Adverse events Measures of tolerability Other outcomes: Quality of life (QoL) Comprehensive geriatric assessment (CGA) Study design Other considerations RCTs, cohort studies and retrospective studies of databases and registries Studies that reported sub-group analyses of elderly people in the abstract were included Only studies published post-2000 in English (or English abstract) were included 4

6 Tolerability measures Adherence to treatment Cycles delivered per patient How many patients completed treatment Relative dose intensity (RDI) Treatment discontinuations Discontinuations due to toxicity Discontinuations due to progressive disease Withdrawal of consent Dose modifications Treatment modifications or interruptions due to toxicity 5

7 Results 8 RCTs 5 sub-group analyses 5716 references identified 5548 references after deduplication 147 references included at stage references excluded at stage 1 91 references (75 studies) included at stage 2 56 references excluded at stage 2 7 pooled analyses 3 prospective comparative cohorts 32 prospective single cohorts 20 retrospective data studies 6

8 Results cont. Breakdown of studies by disease stage Mixed Locally advanced/metastatic breast cancer Early breast cancer Retrospective data Single cohorts Comparative cohorts 1 2 Pooled analyses 3 4 Sub-group analyses 2 3 RCT 4 7

9 Study characteristics Size 48 studies included less than 100 patients 27 studies included more than 100 patients Location 38 studies were multicentre 37 studies were based in single centres 45 studies had centres in Europe Funding 53 studies did not report funding source 15 studies funded by pharmaceutical companies 7 studies funded by research grants 8

10 Patient characteristics Age The definition of elderly varied from 55 years to 75 years The median age of patients across studies ranged from 61 to 78 years Performance status The majority of patients in each study had a performance status of 0-1 Single cohorts included patients with a higher performance status of 2 9

11 PFS/TTP Efficacy outcomes Overall survival Overall response rates Trend for younger patients to fare better Elderly patients derived benefit No statistically significant comparisons Elderly patients gained slightly less benefit Differences were small No statistically significant comparisons Results similar for both groups No statistically significant comparisons *PFS=progression free survival; TTP=time to progression 10

12 Tolerability evidence Treatment adherence Discontinuations Modifications Grade 3-4 adverse events Broadly similar results for both groups for RDI Younger patients generally had higher rates of treatment completion No statistically significant differences reported Trend for higher discontinuation rates in elderly patients Most discontinuations due to toxicity or progressive disease Elderly patients were more likely to have dose modifications Common causes for dose modification was haematological toxicity Trend for higher rates of adverse events in elderly patients Statistically significant results for higher rates of grade 3-4 haematological adverse events in elderly patients 11

13 Quality of life Quality of life results reported in 13/75 studies (3 RCTs, 1 comparative cohort, 8 single cohorts and 1 retrospective study) 11 different quality of life tools used across studies 4 studies reported completion rates for questionnaires Results broadly suggest no significant changes in quality of life throughout treatment 12

14 Comprehensive geriatric assessment Tools used Purpose of tool Activities of Daily Living (ADL) Instrumental ADL (IADL) Vulnerable Elders Survey-13 (VES-13) Charlson Comorbidity Index (CCI) Geriatric depression scale (GDS) Mini-Mental Status (MMS) Karnofsky performance status (KPS) Cumulative Illness Rating Scale for Geriatrics (CIRS-G) Multidimensional Geriatric Assessment (MGA) To assess eligibility for study entry = 1 study As an outcome measure (changes from baseline scores recorded at intervals) = 10 studies 13

15 Conclusions Chemotherapy for elderly people with breast cancer is: o A feasible treatment option o Effective and gives survival benefit o Safe and can be tolerated o Comes with an increased risk of toxic effects Age should not be a barrier to either receiving treatment or being eligible for clinical trials 14

16 Future research Few quality RCTs treating elderly-only population Conduct more clinical trials with an elderlyonly population Include more elderly people in high quality clinical trials RCTs report different outcome measures which cannot be synthesised Implement consistent use of measures to enable meaningful synthesis Trials design to plan collection of supplementary data, e.g. tolerability, QoL No standardised, widely used tools for QoL or CGA Develop and test specific tools for QoL and CGA Implement the standard use of CGA and QoL in clinical trials 15

17 Question time If you require any further information, please get in touch: Gerlinde Pilkington Liverpool Reviews and Implementation Group (LRiG) University of Liverpool Room 2.21a Whelan Building The Quadrangle Brownlow Hill Liverpool L69 3GB Tel: Website: 16

18 Quality assessment We used criteria based on the Centre for Reviews and Dissemination guidance 2 trials were reported as abstracts, therefore not quality assessed Three of the included RCTs were assessed as adequately randomised No trials considered as having adequate concealment of allocation* All trials clearly reported the number of participants randomised Baseline characteristics were presented in all trials Baseline comparability achieved in 7/8 trials All trials reported reasons for withdrawals * A technique used to prevent selection bias by concealing the allocation sequence from those assigning participants to intervention groups Centre for Reviews and Dissemination (CRD). CRD's guidance for undertaking reviews in healthcare: Systematic Reviews (3rd Edition). York: CRD, University of York; 2008; Available from: 17

19 Strengths and limitations Strengths: Comprehensive evidence base Focus on tolerability meaningful for clinicians Enabled comparisons between elderly/younger Limitations: Broad inclusion criteria = heterogeneity Unable to conduct statistical analyses 18