Belinda E. Kiely

How Long Have I Got? Estimating Typical, Best-Case, and Worst-Case Scenarios for Patients Starting First-Line Chemotherapy for Metastatic Breast Cancer: A Systematic Review of Recent Randomized Trials

PURPOSE To estimate scenarios for survival for women with metastatic breast cancer (MBC) who are starting chemotherapy. PATIENTS AND METHODS We sought randomized, first-line chemotherapy trials for MBC published from 1999 to 2009. We recorded median progression-free survival (PFS) and median overall survival (OS) and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We also estimated these scenarios for each OS curve by multiplying its median by four simple multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). Estimates were deemed accurate if they were within 0.75 to 1.33 times the actual value. RESULTS From 36 trials (13,083 women), the mean for median PFS was 7.6 months (interquartile range [IQR], 6.0 to 9.0 months), the mean for median OS was 21.7 months (IQR,18.2 to 24.0 months), and the mean for the ratio of median OS to median PFS was 3.0 (IQR, 2.4 to 3.5). The mean for each OS scenario was worst-case, 6.3 months (IQR, 4.8 to 7.5 months); lower-typical, 11.9 months (IQR, 9.9 to 13.2 months); upper-typical, 36.2 months (IQR, 31.1 to 41.3 months); and best-case, 55.8 months (IQR, 47.5 to 60.2 months). Simple multiples of the median gave accurate estimates of the worst-case scenario in 73% of OS curves, lower-typical in 97%, upper-typical in 95%, and best-case in 96%. OS was longer in trials with higher proportions of estrogen receptor-positive tumors (P = .001) and in trials of trastuzumab-treated human epidermal growth factor receptor 2-positive tumors (P = .001). CONCLUSION Simple multiples of an OS curves median can accurately estimate typical (half to double the median), best-case (triple the median), and worst-case (one quarter of the median) scenarios for survival.

Certain Death in Uncertain Time: Informing Hope by Quantifying a Best Case Scenario

Research informs us that the majority of patients with metastatic cancer desire information about their likely survival duration. The literature also recommends that prognostic information be communicated to those who request it in a manner that is meaningful and realistic, but maintains hope. Knowing these general principles is different than applying them in practice, and when confronted by versions of “how long have I got?” we struggle to find suitable answers. Although patients, caregivers, and health care professionals have identified hope as an integral part of prognostic discussions, the key practical questions of how to define, quantify, and convey realistic hope remain unanswered. The following edited extract from Edward Kennedy’s memoir conveys the importance of trying to answer these questions. “A biopsy the following Monday confirmed that I had a brain tumor—malignant glioma in my left parietal lobe. My wife Vicki and I privately were told that the prognosis was bleak—a few months at most. I respect the seriousness of death—I’ve had many occasions to meditate on its intrusions. But I wasn’t willing to accept the doctor’s prognosis for two reasons. The first was my own obstinate will to carry on in the face of adversity, one of the many habits of discipline that my father instilled in me.... The second was the way the message was delivered. Frankly, it made me furious. I am a realist, and I have heard bad news in my life. I don’t expect or need to be treated with kid gloves. But I do believe in hope. And I believe that approaching adversity with a positive attitude at least gives you a chance for success. Approaching it with a defeatist attitude predestines the outcome: defeat. And a defeatist’s attitude is just not in my DNA.” Kennedy did not receive the hope he desired from his doctors and was left feeling defeated. It may have been that knowing the median survival time, his doctors did indeed feel hopeless. We need to believe hope exists before we can convey it. But how do oncologists find hope? A potential source of hope stems from our experiences with patients who manage to defy the odds and become long-term survivors. Such experiences can help us envision, and therefore convey, hope. A recent example is instructive.

Using scenarios to explain life expectancy in advanced cancer: attitudes of people with a cancer experience

PurposeWe sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy.MethodsOncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer—providing either three scenarios for survival or just the median survival time.ResultsCharacteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001).ConclusionsMost respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.

Estimating typical, best-case and worst-case life expectancy scenarios for patients starting chemotherapy for advanced non-small-cell lung cancer: A systematic review of contemporary randomized trials

INTRODUCTION We sought to estimate life expectancy scenarios for patients starting chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS We searched for randomized first-line chemotherapy trials published from January 2000 to April 2008. We recorded median time to progression (TTP) and median overall survival (OS) and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical) and 10th (best-case). For each OS curve we divided these percentiles (scenarios) in turn by the median to determine if a simple relationship existed between each scenario and the median. RESULTS From 60 trials (29,657 patients), the mean for median TTP was 4.8 months (interquartile range [IQR] 4.0-5.3), the mean for median OS was 9.2 months (IQR 8.1-10.1) and the mean ratio for median OS to median TTP was 2.0 (IQR 1.7-2.2). The mean (IQR) in months for each OS scenario was: worst-case, 2.4 (1.9-2.7); lower-typical, 4.8 (4.2-5.4); upper-typical, 16.3 (14.4-18.1); and best-case, 25 (21.0-28.0). The mean values (IQR) for each scenario divided by the median were: worst-case/median 0.26 (0.21-0.29); lower-typical/median 0.53 (0.5-0.57); upper-typical/median 1.81 (1.69-1.93) and best-case/median 2.84 (2.57-3.19). These values can be approximated by the simple multiples: 0.25, 0.5, 2 and 3. Independent predictors of longer OS were ECOG PS<2, adenocarcinoma, and longer TTP; all p-values<0.001. CONCLUSION Simple multiples of an OS curves median provided accurate estimates of typical (half to double the median), best-case (triple the median), and worst-case (one quarter of the median) life expectancy scenarios for patients starting chemotherapy for advanced NSCLC.

Thinking and Talking About Life Expectancy in Incurable Cancer

Most patients with incurable cancer want information about the impact cancer will have on their future, and many want specific estimates of the most likely, best case, and worst case scenarios for survival. With improved understanding of life expectancy, patients are better equipped to make appropriate treatment decisions and plans for the future. Although physicians acknowledge that patients with incurable cancer want prognostic information and benefit from this, most struggle to provide it and experience difficulty in making reliable estimates, communicating them, and tailoring the information to the individual patient. In this review we address some of the implications that arise from thinking and talking about life expectancy with people who have incurable cancer, particularly those considering first- or second-line chemotherapy.

Estimating scenarios for survival time in men starting systemic therapies for castration-resistant prostate cancer: A systematic review of randomised trials

BACKGROUND We sought to estimate worst-case, typical and best-case scenarios for survival in men starting systemic therapies for castration resistant prostate cancer (CRPC). METHODS We sought randomised phase 3 trials of systemic therapies for CRPC and recorded the following percentiles (represented scenario) from Kaplan-Meier overall survival (OS) curves: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We determined the accuracy of using simple multiples of the median OS to estimate the other selected percentiles from each curve: 0.25 for 90th, 0.5 for 75th, 2 for 25th and 3 for 10th. Estimates were deemed accurate if within 0.75-1.33 times the actual value. FINDINGS We reviewed 23 trials (13,909 men) with 48 treatment groups including 28 of chemotherapy, and three of novel hormonal agents. In trials of first-line docetaxel, the mean (interquartile range) for median OS was 19 months (17-20), and for each scenario was: worst-case 7 months (6-8); lower-typical 12 months (11-13); upper-typical 29 months (27-31); and best-case 40 months (34-44). For trials of novel hormonal agents after chemotherapy the mean values were: median OS 17 months, worst-case 5 months, lower-typical 9 months, upper-typical 24 months and best-case not reported. Simple multiples of the median gave accurate estimates of the worst-case scenario in 72% of OS curves, lower-typical in 89%, upper-typical in 84% and best-case in 84%. INTERPRETATION Simple multiples of the median OS from randomised trials provided accurate estimates of worst-case, typical and best-case scenarios for survival time in men starting systemic therapies for CRPC.

Incidence of metastatic breast cancer in an Australian population-based cohort of women with non-metastatic breast cancer at diagnosis.

Objectives: To estimate the incidence of metastatic breast cancer (MBC) in Australian women with an initial diagnosis of non‐metastatic breast cancer.

Survival times of women with metastatic breast cancer starting first-line chemotherapy in routine clinical practice versus contemporary randomised trials.

Survival times of women starting first‐line chemotherapy for metastatic breast cancer (MBC) in routine clinical practice were determined and compared with those from a systematic review of randomised clinical trials.

Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort

Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments.

More than just the median: Calculating survival times for patients with HER2 positive, metastatic breast cancer using data from recent randomised trials

OBJECTIVES To estimate worst-case, typical and best-case scenarios for survival as a communication aid for managing patients with HER2-positive metastatic breast cancer (MBC) starting HER2-targeted therapies. METHODS We sought randomised trials of HER2-targeted therapies and recorded the following percentiles (representative scenarios) from each OS curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We then tested whether we could estimate these percentiles for each OS curve by multiplying its median by four simple multiples: 0.25 (to derive the 90th percentile), 0.5 (75th), 2 (25th) and 3 (10th). Estimates were deemed accurate if within 0.75-1.33 times the actual value. RESULTS We identified 15 trials with 4798 patients. For first-line, single-agent HER2-targeted therapy (15 treatment groups), the median (interquartile range [IQR]) for median OS was 33.3 months (29.1-38.4), and for each percentile was: 90th 9.5 months (7.7-11.0); 75th 19.2 months (16.4-20.8); and 25th 50.6 months (47.1-63.3). The 10th percentile was unavailable for all treatment groups. For first-line dual HER2-targeted therapy (1 treatment group), the median OS was 56.5 months. Simple multiples of the median OS accurately estimated the: 90th percentile in 79%; 75th percentile in 100%; and 25th percentile in 89% of OS curves. CONCLUSIONS Surprisingly little is known of survival beyond the median for HER2-positive MBC. Longer trial follow-up is required to help clinicians estimate and explain the best-case scenario. Simple multiples of the median OS provide a reasonable framework for estimating then explaining survival times to patients.