Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy.

BACKGROUND: We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies. MATERIALS AND METHODS: We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). RESULTS: We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS. CONCLUSIONS: Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.

Measuring serum oestrogen levels in breast cancer survivors using vaginal oestrogens: a systematic review.

PURPOSE: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability. METHODS: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included. RESULTS: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported. CONCLUSIONS: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.

Timing of prognostic discussions in people with advanced cancer: a systematic review.

PURPOSE: Many people with cancer (patients) want to know their prognosis (a quantitative estimate of their life expectancy) but this is often not discussed or poorly communicated. The optimal timing of prognostic discussions with people with advanced cancer is highly personalised and complex. We aimed to find, organise, and summarise research regarding the timing of discussions of prognosis with people with advanced cancer. METHODS: We conducted a systematic review of publications from databases, clinical practice guidelines, and grey literature from inception to 2023. We also searched the reference lists of systematic reviews, editorials, and clinical trial registries. Eligibility criteria included publications regarding adults with advanced cancer that reported a timepoint when a discussion of prognosis occurred or should occur. RESULTS: We included 63 of 798 identified references; most of which were cross-sectional cohort studies with a range of 4-9105 participants. Doctors and patients agreed on several timepoints including at diagnosis of advanced cancer, when the patient asked, upon disease progression, when there were no further anti-cancer treatments, and when recommending palliative care. Most of these timepoints aligned with published guidelines and expert recommendations. Other recommended timepoints depended on the doctor's clinical judgement, such as when the patient 'needed to know' or when the patient 'seemed ready'. CONCLUSIONS: Prognostic discussions with people with advanced cancer need to be individualised, and there are several key timepoints when doctors should attempt to initiate these conversations. These recommended timepoints can inform clinical trial design and communication training for doctors to help improve prognostic understanding.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study.

PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

Patients' perception of the benefits of palliative systemic therapy for advanced cancer.

BACKGROUND: Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy. AIM: To determine patient perceptions of palliative systemic therapy benefits in advanced cancer. METHODS: We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0-10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4-7 QOL and LOL equal; >7 LOL most important). Patient-oncologist discordance was defined as a ≥4-point difference. RESULTS: The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient-oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%). CONCLUSION: At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions.

Pertuzumab study in the neoadjuvant setting for HER2-positive nonmetastatic breast cancer in Australia (PeRSIA).

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

Finding My Way-Advanced: can a web-based psychosocial intervention improve the mental quality of life for women with metastatic breast cancer vs attention-control? Study protocol of a randomised controlled trial.

BACKGROUND: Women living with metastatic breast cancer (MBC) are at risk of significantly impaired quality of life (QOL), symptom burden, distress and fear of progression, and unmet needs, yet they face barriers to accessing evidence-based psychosocial treatments. Our group therefore developed Finding My Way-Advanced (FMW-A), a web-based self-guided psychosocial program for women with MBC. This study aims to assess its efficacy in improving mental and other QOL domains, distress, fear of progression, unmet needs, and health service utilisation. METHODS: The multi-site randomised controlled trial (RCT) will enrol 370 Australian participants. Eligible participants are adult (18 years +) women diagnosed with MBC, with a life expectancy of 6 months or more, with sufficient English-language literacy to provide informed consent. Participants will be identified, screened and referred from one of 10 Australian sites, or via self-referral in response to advertisements. Participants complete four online questionnaires: prior to accessing their program ('baseline'), 6 weeks later ('post-intervention'), then 3 months and 6 months post-intervention. Consenting participants will be randomised to either FMW-A (intervention), or Breast Cancer Network Australia's (BCNA) online/app resource My Journey (minimal intervention attention-control). This is a single-blind study, with randomisation computer-generated and stratified by site. FMW-A is a 6-module program addressing some of the most common issues experienced by women with MBC, with BCNA control resources integrated within the 'resources' section. All modules are immediately accessible, with an additional booster module released 10 weeks later. The primary outcome is mental QOL; statistical criteria for superiority is defined as a 4-point difference between groups at post-treatment. Secondary outcomes include other QOL domains, distress, fear of progression, health service use, intervention adherence, and user satisfaction. DISCUSSION: This will be the first adequately powered RCT of a self-directed online intervention for women with MBC. If efficacious, FMW-A will help address two national key priorities for management of MBC - enhancing QOL and reducing symptom burden. FMW-A has the potential to address unmet needs and overcome access barriers for this overlooked population, while reducing health system burden. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 29/10/2021. Trial ID ACTRN12621001482853p.  https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382714&isReview=true.

Long term risk of distant metastasis in women with non-metastatic breast cancer and survival after metastasis detection: a population-based linked health records study.

OBJECTIVES: To estimate the long term risk of distant metastases (DM) for women with initial diagnoses of non-metastatic breast cancer; to estimate breast cancer-specific and overall survival for women with DM. DESIGN: Population-based health record linkage study. SETTING, PARTICIPANTS: Women diagnosed with localised or regional primary breast cancer recorded in the NSW Cancer Registry, 2001-2002. MAJOR OUTCOME MEASURES: Time from breast cancer diagnosis to first DM, time from first DM to death from breast cancer. SECONDARY OUTCOME: time to death from any cause. RESULTS: 6338 women were diagnosed with non-metastatic breast cancer (localised, 3885; regional, 2453; median age, 59 years [IQR, 49-69 years]). DM were recorded (to 30 September 2016) for 1432 women (23%; median age, 62 years [IQR, 51-73 years]). The 14-year cumulative DM incidence was 22.2% (95% CI, 21.1-23.2%; localised disease: 14.3% [95% CI, 13.2-15.4%]; regional disease: 34.7% [95% CI, 32.8-36.6%]). Annual hazard of DM was highest during the second year after breast cancer diagnosis (localised disease: 2.8%; 95% CI, 2.3-3.3%; regional disease: 9.1%; 95% CI, 7.8-10.3%); from year five it was about 1% for those with localised disease, from year seven about 2% for women with regional disease at diagnosis. Five years after diagnosis, the 5-year conditional probability of DM was 4.4% (95% CI, 3.7-5.1%) for women with localised and 10.4% (95% CI, 9.1-12.0%) for those with regional disease at diagnosis. Median breast cancer-specific survival from first DM record date was 28 months (95% CI, 25-31 months); the annual hazard of breast cancer death after the first DM record declined from 36% (95% CI, 33-40%) during the first year to 14% (95% CI, 11-18%) during the fourth year since detection. CONCLUSIONS: DM risk declines with time from diagnosis of non-metastatic breast cancer, and the annual risk of dying from breast cancer declines with time from initial DM detection. These findings can be used to inform patients at follow-up about changes in risk over time since diagnosis and for planning health services.

Prevalence and severity of scanxiety in people with advanced cancers: a multicentre survey.

PURPOSE: Scan-associated anxiety ('scanxiety') is a problem for people with advanced cancer. We aimed to determine the prevalence, severity and associations of scanxiety in this population. METHODS: People with advanced cancer and a computed tomography scan within the last 4 months completed a multicentre survey including self-rated presence (yes/no) and severity (distress thermometer, 0-10) of scanxiety, state anxiety (STAI-6), clinical anxiety and depression (HADS), and fear of progression (FOP-Q-SF). Associations with scanxiety were evaluated. RESULTS: There were 222 participants: mean age 64 years (range 26 to 91), female (61%), most common cancer types (breast 37%, lung 19%, colorectal 16%) and > 1 year since cancer diagnosis (82%). Sixty-two percent had a scan within the last month, and 70% reported waiting > 2 days for the result. Over half (55%) of participants experienced scanxiety. On multivariable analysis, scanxiety was more prevalent in participants who were younger (mean age 62 years with v 66 years without scanxiety, p = 0.02) and more remote (v major city, OR 2.6, p = 0.04). Among participants with scanxiety, the mean severity score was 6 (range 1-10) with peak severity occurring when waiting for scan results. On multivariable analysis, scanxiety was 1.2 points higher in participants who had been diagnosed within the past year (v > 1 year, p = 0.04) and was higher in participants who had higher STAI-6 scores (ß = 0.06, p = 0.004). CONCLUSION: Scanxiety is common and can be severe. Strategies to reduce scanxiety are needed.

Using three scenarios to explain life expectancy in advanced cancer: attitudes of patients, family members, and other healthcare professionals.

AIM: To evaluate a web-based tool for estimating and explaining three scenarios for expected survival time to people with advanced cancer (patients), their family members (FMs), and other healthcare professionals (HCPs). METHODS: Thirty-three oncologists estimated the "median survival of a group of similar patients" for patients seeking quantitative prognostic information. The web-based tool generated worst-case, most likely, and best-case scenarios for survival based on the oncologist's estimate. Oncologists presented the scenarios to each patient and provided a printed summary to patients, FMs, and HCPs. Attitudes to the information were assessed by questionnaires. Observed survival for each patient was compared with the oncologist's estimated survival and the three scenarios. RESULTS: Prognosis was discussed with 222 patients: median age 67 years; 61% male; most common primary sites pancreas 15%, non-small-cell lung 15%, and colorectal 12%. The median (range) for observed survival times was 9 months (0.5-43) and for oncologist's estimated survival times was 12 months (2-96). Ninety-one percent of patients, 91% of FMs, and 84% of HCPs agreed that it was helpful having life expectancy explained as three scenarios. The majority (77%) of patients judged the information presented about their life expectancy to be the same or better than they had expected before the consultation. The survival estimates met a priori criteria for calibration, precision, and accuracy. CONCLUSIONS: Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.

Cardiac assessment in Australian patients receiving (neo)adjuvant trastuzumab for HER2-positive early breast cancer: a population-based study.

PURPOSE: Cardiac function assessment is important for detecting and managing trastuzumab-associated cardiotoxicity. Our study estimates rates and predictors of cardiac assessment among patients receiving trastuzumab for HER2-positive early breast cancer (HER2+EBC) in Australia. METHODS: We conducted a retrospective cohort study of Australians initiating (neo)adjuvant trastuzumab for HER2+EBC between 1 January 2015 and 15 April 2019. We used administrative claims to determine the number of patients receiving guideline-recommended assessment, i.e. evidence of baseline cardiac assessment (between 120 days before and 30 days after trastuzumab initiation) and regular on-treatment cardiac assessments (at least every 120 days). We examined factors associated with baseline and regular on-treatment cardiac assessment. RESULTS: Our study includes 5621 patients (median age 56 years), of whom 4984 (88.7%) had a baseline cardiac function test. Among 4280 patients with at least 12 months of follow-up, 2702 (63.1%) had guideline-recommended cardiac assessment. Rates of guideline-recommended assessment increased with later year of diagnosis (60.9% in 2015 vs 68.3% in 2018, OR 1.34, 95% CI 1.06-1.69). Patients with higher baseline comorbidities and greater socioeconomic disadvantage were less likely to have guideline-recommended cardiac assessment. Cardiac assessment practices varied by State/Territory. There was no association between baseline cardiac risk or anthracycline use and the likelihood of receiving guideline-recommended cardiac assessment. CONCLUSION: The majority of patients receiving (neo)adjuvant trastuzumab had guideline-recommended baseline and on-treatment cardiac assessment. Variations in cardiac assessment predominantly related to system-level factors, such as year of diagnosis and geography, rather than individual patient factors.

Relationship between sleep disturbance, symptoms, and alcohol use in breast cancer survivors attending Sydney Cancer Survivorship Clinic.

PURPOSE: We sought to determine the association between 'trouble sleeping', alcohol intake, hot flashes, and quality of life (QOL) in early-stage breast cancer survivors attending the Sydney Cancer Survivorship Clinic (SCSC). METHODS: Survivors who had completed primary adjuvant treatment completed questionnaires assessing the following: symptoms, QOL (mean global score on FACT-G), and alcohol intake (drinks per day for past week), on the first visit to SCSC. Trouble sleeping and hot flashes were scored from 0 (no trouble at all) to 10 (worst I can imagine), with scores ≥ 4 classified as at least moderate and ≥ 7 severe. RESULTS: 238 breast cancer survivors attended SCSC from September 2013 to May 2019, with data available for 227 (median age 53 years; 70% on endocrine therapy). Trouble sleeping was at least moderate in 54% and severe in 19%. 47% reported consuming alcohol (mean 4.9 drinks/week). Scores for trouble sleeping were no different between survivors reporting alcohol consumption and not (mean 4.13 vs. 3.6; p = 0.17). Survivors reporting at least moderate trouble sleeping (vs. less than moderate) were no more likely to drink alcohol (OR 1.74, 95% CI 0.96-3.14, p = 0.067) but had poorer mean QOL scores (69.1 vs. 78.3; p = 0.0006). Survivors reporting at least moderate hot flashes (vs. less than moderate) were more likely to report at least moderate trouble sleeping (OR 3.78, 95% CI 2.02-6.71, p < 0.0001) and had worse mean QOL scores (68 vs. 78; p = 0.001). CONCLUSION: Trouble sleeping is common amongst breast cancer survivors and associated with hot flashes and poorer QOL, but not with self-reported alcohol consumption.

Experiences with scans and scanxiety in people with advanced cancer: a qualitative study.

PURPOSE: Scan-associated anxiety ('scanxiety') in people with advanced cancer is a common clinical problem. This study aims to explore the experiences of scans and scanxiety in people with advanced cancer, including their strategies to reduce scanxiety. METHODS: Semi-structured qualitative interviews were conducted with people with advanced cancers who had a computed tomography scan for monitoring of their cancer. Data was analysed with an interpretivist approach using framework analysis. RESULTS: Interviews with 16 participants identified three key themes: the scan experience, the scanxiety experience and coping with scans. Scans were viewed as a routine and normal part of cancer care. Scanxiety was experienced differently by each person. Scanxiety often related to the scan result rather than the scan and led to psycho-cognitive manifestations. Adaptive coping strategies were often self-derived. CONCLUSION: People with advanced cancer experience scanxiety, but often accept scanxiety as a normal part of the cancer process. The findings fit within a transactional model of stress and coping, which influences the level of scanxiety for each individual. Quantitative research to determine the scope of scanxiety will be useful to develop formal approaches to reduce scanxiety.

Correction: Treatment patterns and survival in HER2-positive early breast cancer: a whole-of-population Australian cohort study (2007-2016).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Communicating prognostic information: what do oncologists think patients with incurable cancer should be told?

BACKGROUND: People with incurable cancer require information about their prognosis to make informed decisions about their future. AIMS: To determine the frequency, form and documentation of prognostic discussions between oncologists and their patients with incurable cancer. METHODS: We surveyed medical oncologists in Australia and New Zealand about their practices communicating prognosis. RESULTS: A total of 206 medical oncologists completed the survey. Respondent characteristics were: median age 40 years (range 27-75), female 51%, trainee 22%; and 71% had completed specific training on communicating prognosis. Respondents reported discussing prognosis with a patient a median of 10 times per month (interquartile range 4-15); 88% reported explaining that 'the cancer is incurable' to all their patients with incurable cancer and 84% reported always or usually providing a quantitative estimate of survival time. The preferred method for explaining expected survival time (EST) was providing 'multiple ranges of time with probabilities, for example best-case, typical and worst-case scenarios' (52% of respondents). The most frequently reported barriers to discussing EST were: 'family members requesting that prognostic information not be discussed' (57% of respondents), and 'not knowing the EST' (46% of respondents). Twenty percent reported always documenting prognostic discussions and the EST in the patient's medical record, and 11% reported always documenting this information in their letters to other doctors. CONCLUSIONS: Most oncologists reported providing quantitative estimates of EST to their patients with incurable cancer, but very few reported documenting this information. Methods to help oncologists estimate, explain and document survival time are needed to improve communication of prognosis.

Treatment patterns and survival in HER2-positive early breast cancer: a whole-of-population Australian cohort study (2007-2016).

BACKGROUND: Randomised clinical trials (RCTs) demonstrate that trastuzumab improves survival in patients with human epidermal growth factor 2-positive early breast cancer (HER2 + EBC), but real-world patients and clinical practice often differ from RCTs. We examine real-world treatment patterns and outcomes associated with trastuzumab for HER2 + EBC. METHODS: We identified all Australians dispensed trastuzumab for HER2 + EBC between 1/1/2007 and 30/6/2016. We estimated the proportion of patients completing 12 months of treatment (defined as ≥350 days of exposure within 540 days of initiation). We estimated overall survival (OS) and recurrence-free survival (RFS) by using trastuzumab dispensing for metastatic breast cancer as a surrogate for recurrence. RESULTS: Our study included 14,644 patients. Among patients with ≥540 days of follow-up (n = 11,903), 67.4% completed 12 months of trastuzumab. OS rates at 5 and 9 years were 92.7 and 87.9%, and RFS rates at 5 and 9 years were 86.8 and 81.4%, respectively. Patients who completed 12 months of trastuzumab had a 9-year OS rate of 90.2% compared with 86.2% among patients receiving <12 months of therapy (adjusted HR 0.71, 95% CI 0.62-0.81). CONCLUSIONS: Real-world HER2 + EBC patients are less likely to complete 12 months of trastuzumab than some clinical trial counterparts but have survival outcomes comparable to those reported in landmark RCTs.

Accuracy and Prognostic Significance of Oncologists' Estimates and Scenarios for Survival Time in Advanced Gastric Cancer.

BACKGROUND: Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists' estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. MATERIALS AND METHODS: Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists' estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise (<33% within 0.67-1.33 times the OST); independently predictive of overall survival (OS); and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario). RESULTS: Oncologists' estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67-1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists' estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. CONCLUSION: Oncologists' estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. IMPLICATIONS FOR PRACTICE: Results of this study demonstrate that oncologists' estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003-2015).

BACKGROUND: Older patients with HER2-positive metastatic breast (HER2 + MBC) cancer are underrepresented in clinical trials. We aim to describe the treatment patterns and overall survival (OS) for older women receiving trastuzumab for HER2 + MBC. METHODS: Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for Australian women ≥ 65 years initiating trastuzumab for HER2 + MBC between 2003 and 2015. We describe time-on-trastuzumab; type and timing of other cancer treatments; rates of cardiac monitoring; and OS from trastuzumab initiation for HER2 + MBC. RESULTS: Of 5404 women initiating trastuzumab for HER2 + MBC, 1583 (29%) were ≥ 65 years old, and the proportion of older patients increased from 20% in 2003 to 38% in 2015. The median age for older women was 73 years and 516 (33%) were ≥ 75 years. Most older patients (92%) received ≥3medicines for comorbidities other than cancer. Median (IQR) time on trastuzumab was 14.1 months (5.9-32.1) and on all chemotherapy was 5.6 months (3.3-10.8). 74% received ≥1 chemotherapy agent and 56% received endocrine therapy. Half (49%) of patients had a cardiac assessment prior to initiating trastuzumab and overall 1228 (76%) had ≥1 cardiac assessment during the study period. At a median follow-up of 6 years, 73% of patients had died and the median OS was 25.6 months (IQR 10.7-58.7). CONCLUSIONS: Older patients comprise a growing proportion of patients treated with HER2-targeted therapies in the real-world but they remain underrepresented in trials of these agents. Few trials report duration or OS estimates for older patients but our estimates are similar to those from trials that have. Although cardiac monitoring was a requirement of accessing trastuzumab during our study period, many patients did not undergo a cardiac assessment.

Association between ribociclib and changes in creatinine in patients with hormone receptor positive metastatic breast cancer.

Combination ribociclib and aromatase inhibitors are currently the preferred treatment in Australia for newly diagnosed hormone receptor positive metastatic breast cancer in the absence of visceral crisis. In our case series of 32 patients, 28% experienced grade 1 elevations in creatinine, a toxicity that was under-recognised in large phase III studies. Creatinine rise appears to be due to a reversible inhibition of renal efflux transporters rather than an acute kidney injury in the majority of cases.