Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia

doi:10.1016/j.jgo.2015.06.001

Journal of Geriatric Oncology

Volume 6, Issue 5, September 2015, Pages 387-394

https://doi.org/10.1016/j.jgo.2015.06.001 Get rights and content

Abstract

Objectives

The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting.

Materials and Methods

Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65–74 vs. 75–84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis.

Results

Of 1439 patients, 363, 352, and 106 were aged 65–74, 75–84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65–74-, 75–84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%).

Conclusion

Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.

Introduction

Cancer is predominantly an age-related disease, with approximately 60% of new cancer diagnoses and 70% of all cancer deaths occurring in those aged over 65 years.¹ This age-related risk is illustrated in the epidemiology of colorectal cancer (CRC) in Australia, where the average age at diagnosis is 69.3 years, with CRC accounting for 9.3% of all cancer deaths.²

There is a paucity of safety and efficacy data in elderly patients due to underrepresentation in clinical trials, where the median age of patients enrolled is typically 60–65 years. This is partly due to a reluctance of investigators to enrol elderly patients onto clinical trials, along with stringent eligibility criteria, such that elderly patients are excluded based on poor functional status, major organ dysfunction, cognition, or even chronological age alone.³ There is also a paucity of data related to the surgical approach to elderly patients, both for those with an intact primary and those with resectable metastatic disease.

Previous studies suggest that a significant proportion of elderly patients in routine practice do not receive treatment despite evidence suggesting that current combination chemotherapy regimens for metastatic CRC (mCRC) are equally tolerable for older persons enrolled on clinical trials, with similar treatment benefits observed compared to younger patients.⁴ Notably, however, studies enrolling only elderly patients[5], [6] have not been able to confirm these findings, raising questions about the role of upfront combination chemotherapy in older patients.

The addition of bevacizumab to chemotherapy in the treatment of mCRC has resulted in clinically significant improvements in progression-free and overall survival (OS),⁷ with evidence suggesting a similar clinical benefit across all age groups,[8], [9] including studies only enrolling elderly patients.¹⁰ Bevacizumab is generally well tolerated, although increased toxicity rates, particularly thromboembolic events, have been reported among older patients.[9], [10], [11]

The purpose of this study was to review treatment patterns and outcomes in elderly patients with mCRC in a non-clinical trial setting, according to three age subgroups: 65–74, 75–84, and ≥ 85 years. Of particular interest were the impact of performance status and comorbidity on clinician decision-making. Along with this, the reason for any elderly patient not receiving active treatment was prospectively recorded. The findings of this study reflect current Australian practice in managing elderly patients with mCRC.

Section snippets

Materials and Methods

Secondary analysis of prospectively collected data of patients with mCRC aged ≥ 65 years identified from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry.¹² This database was initiated between BioGrid Australia and Roche Australia in 2009 to prospectively collect data for consecutive patients with newly diagnosed mCRC, including those who do not receive active therapy. Data were collected by clinicians at the point-of-care and entered into local research repositories at

Statistical Analysis

In this analysis, patients with newly diagnosed mCRC, including those who had prior treatment for an early stage CRC, were enrolled from 1 July 2009 to 30 June 2014. The cohort of elderly patients was analysed according to three age subgroups: 65–74, 75–84, and ≥ 85 years, to explore differences in clinicopathologic features, treatment delivery, adverse events, and outcomes.

Descriptive statistics and the chi-square test were used to analyse differences in characteristics between the age groups.

Patient Characteristics

Of 1439 patients enrolled in the mCRC registry, 821 patients (57%) were aged ≥ 65 years. In this elderly cohort, 363 (44%), 352 (43%), and 106 (13%) patients were aged 65–74, 75–84, and ≥ 85 years, respectively. Older patients were more likely to be female (35% vs. 43% vs. 54%, P < 0.01), have a worse performance status (PS) (PS ≥ 2: 17% vs. 29% vs. 50%, P < 0.001) and have primary tumours located in the right colon (28% vs. 35% vs. 43%, P < 0.01) (Table 1). Across the three age groups, the most common

Discussion

The management of mCRC in elderly patients poses multiple challenges. Treatment decisions are largely based on randomised clinical trials that enrol predominantly younger patients, with modifications then made due to a patient's functional status, underlying comorbidities, risk of treatment-related morbidity, ability to tolerate adverse events, and individual patient wishes. Ultimately, a decision may be made to pursue a standard therapy, a standard therapy with modifications or no treatment.

Conclusion

While a significant proportion of elderly patients in our cohort received chemotherapy, concurrent bevacizumab appears to be underutilised, reflecting ongoing uncertainty of its clinical benefit and toxicity in the older population. Medical oncologists need to be mindful of not excluding patients from treatment on the basis of age alone, although the data supporting upfront combination chemotherapy in elderly patients is limited. Careful patient selection is warranted and validated geriatric

Funding

This work was supported by Roche Products Pty Limited (Australia); Roche has provided financial assistance for the development, installation, and maintenance of this clinical database.

Disclosures and Conflict of Interest Statements

KF has received honoraria from Roche Products Pty Limited (Australia). LN has received honoraria and other renumeration from Roche Products Pty Limited (Australia). All remaining authors have declared no conflicts of interest.

Author Contributions

Study concepts: S. Parakh, H. Wong, P. Gibbs, D. Yip Study design: S. Parakh, H. Wong, P. Gibbs, D. Yip Data acquisition: S. Parakh, H. Wong, R. Rai, D. Yip Quality control of data and algorithms: S. Parakh, H. Wong, D. Yip Data analysis and interpretation: S. Parakh, H. Wong, P. Gibbs, D. Yip Statistical analysis: H. Wong Manuscript preparation: S. Parakh, H. Wong, D. Yip Manuscript editing: S. Parakh, H. Wong, R. Rai, S. Ali, K. Field, J. Shapiro, R. Wong, L. Nott, P. Gibbs, D. Yip Manuscript

Acknowledgements

The authors wish to acknowledge BioGrid Australia, Michael Harold, and all sites and clinicians participating in the TRACC registry.

References (21)

M.T. Seymour et al.
Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial
Lancet
(2011)
D. Cunningham et al.
Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial
Lancet Oncol
(2013)
M.E. Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)
M.T. Seymour et al.
Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial
Lancet
(2007)
M. Koopman et al.
Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial
Lancet
(2007)
M. Ducreux et al.
Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial
Lancet Oncol
(2011)
T.J. Price et al.
Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C
Ann Oncol
(2012)
J. Ferlay et al.
GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]
(2013)
Australian Institute of Health and Welfare et al.
Cancer in Australia: an overview, 2012
C.A. Townsley et al.
Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials
J Clin Oncol
(2005)

There are more references available in the full text version of this article.

Cited by (21)

Geriatric factors associated with overall survival in older patients with metastatic colorectal cancer
2024, Clinics and Research in Hepatology and Gastroenterology
Advanced age in patients with colorectal cancer is a factor of poor prognosis, but little is known about geriatric factors associated with survival and chemotherapy prescription in frail elderly patients. Our research sought to investigate these factors in older patients with metastatic colorectal cancer (mCRC).
patients aged ≥75 years, who were treated for mCRC and have had a Comprehensive Geriatric Assessment (CGA) due to their frailty, were included in this multicenter practice study in the Loire Valley region (France). With initial patient care for mCRC as the starting point, demographic, oncological, geriatric and survival data were collected from the regional cancer database and the medical record of each patient. We analyzed overall survival and chemotherapy prescription, according to the geriatric factors of the CGA.
108 patients were enrolled (mean age 84.0 +/- 4.5 years; 57.4 % men), among whom 53 (49 %) received at least one line of chemotherapy. The median overall survival [95 %CI] was 8.05 [5.6–12.0] months. In univariate analysis, prescription of chemotherapy was associated with the number of severe co-morbidities, number of co-medications, G8 score, BMI, MMSE score, IADL and ADL scores, Lee index and Balducci criteria. Survival was significantly associated with chemotherapy, ADL and IADL scores, G8 score, repeated falls, number of severe co-morbidities, MMSE score, Lee index and Balducci criteria. In multivariate analysis, only the ADL score (HR [95 %CI]: 0.74 [0.55–0.99], p = 0.04), number of severe co-morbidities (HR [95 %CI]: 1.62 [1.06–2.47], p = 0.03) and repeated falls (HR [95 %CI]: 3.54 [1.70–7.39], p < 0.001) were significantly associated with survival.
in frail elderly patients with mCRC, dependency, co-morbidities and repeated falls are independent factors associated with survival. As such, there could be merit in taking these into consideration before the choice of oncological treatment is made.
Efficacy and Safety of Bevacizumab Combined With First-Line Chemotherapy in Elderly (≥75 Years) Patients With Metastatic Colorectal Cancer: A Real-World Study
2020, Clinical Colorectal Cancer
Although elderly patients are the first concerned by colorectal cancer (CRC), they are underrepresented in clinical trials. The real-world CASSIOPEE study was thus conducted in elderly patients treated for metastatic CRC (mCRC).
This French prospective, multicenter, noninterventional study aimed to estimate 1-year progression-free survival (PFS) and overall survival (OS), and describe treatments, patient autonomy (Instrumental Activities of Daily Living; Balducci scale), and safety over 24 months, in patients older than 75 with mCRC, starting first-line bevacizumab plus chemotherapy (NCT01555762).
From 2012 to 2014, 402 patients were included (safety population: n = 383, efficacy population: n = 358). Patient characteristics were as follows: mean age, 81 ± 4 years (<80 years, 46%; 80-85 years, 44%; >85 years, 10%); men, 52%; colon primary tumor, 80%; main metastatic site, liver 66%; Eastern Cooperative Oncology Group performance 0-1, 81%. Median PFS was 9.1 months (95% confidence interval [CI]: 8.3–10.2). It was superior for patients ≤85 years (<80 years: 9.3 months; 80-85 years: 9.5 months) compared with patients >85 years (8.3 months). Median OS was 19.0 months (95% CI, 16.5-21.5) and decreased in the 2 oldest groups (20.6, 17.8, and 13.0 months). Autonomy assessments decreased over time leading to nonconclusive results. Twenty-six percent of patients experienced serious adverse events (SAEs): 7% bevacizumab-related SAEs, and 6% bevacizumab-targeted SAEs. Two fatal bevacizumab-related adverse events were reported (hemorrhagic stroke and intestinal ischemia).
This large French real-world study showed that medically fit older patients with mCRC could have a benefit/risk balance similar to that of younger patients when treated with first-line bevacizumab plus chemotherapy. Improvements in geriatric assessments are needed to better define this population.
Patterns of Use, Safety, and Effectiveness of Targeted Therapies in First-Line Treatment of Metastatic Colorectal Cancer According to Age: The STROMBOLI Cohort Study
2019, Clinical Colorectal Cancer
Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age.
Two field cohorts of patients initiating bevacizumab or cetuximab for first-line mCRC were pooled. Patients characteristics, use, and safety were compared between younger and elderly patients (<75 vs. ≥75 years). Two-year overall survival (OS) and progression-free survival (PFS) were estimated in both age groups using the Kaplan–Meier method adjusted on factors associated with death or progression identified with Cox multivariate modeling.
Eight hundred patients (n = 411, 51.4% bevacizumab) were included: 498 (62.3%) male, median age 64 years, 118 (14.8%) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. Elderly patients (n = 126, 15.8%) were more often treated with 5-fluorouracil alone than younger. Severe adverse events were equivalent across age groups. ECOG-PS ≥1, abnormal hemoglobin, and abnormal alkaline phosphatases were associated with a higher risk of death; OS adjusted on these factors was similar between elderly and younger patients. ECOG-PS ≥1, lung metastases, abnormal hemoglobin, and abnormal creatinine clearance were associated with a higher risk of progression or death; PFS adjusted on these factors was similar across groups.
Despite treatment adaptations, elderly patients could benefit from targeted therapies as younger without safety warning.
Impact of comorbidity and frailty on prognosis in colorectal cancer patients: A systematic review and meta-analysis
2018, Cancer Treatment Reviews
Citation Excerpt :
Regardless of the comorbidity indices and cut-offs used in these studies, severe comorbidity was significantly associated with an increased overall mortality in CRC patients (Supplemental Tables 2 and 3). Similarly, except in four studies [39,42,51,58], mildly comorbid patients showed poor overall survival. The magnitude of mortality risk associated with comorbidity, however, decreased steadily with CRC stage at diagnosis [28,29,54,59,61].
Colorectal cancer (CRC) is largely diagnosed at old age, when comorbidities and frailty are common and might be important prognostic factors of CRC. We aimed to systematically review epidemiological evidence on the prognostic role of comorbidity and frailty in CRC patients.
We systematically searched the PubMed and Web of Science databases up to August 08, 2017 for observational studies that used a standardized index to assess comorbidity or frailty, investigated and reported odds ratios (OR) or hazard ratios (HR) of their associations with any of the following CRC prognostic outcomes: thirty-day, overall or CRC-specific mortality and disease-free or recurrence-free survival. The study was conducted using standard meta-analysis methodology.
Thirty-seven cohort studies were identified and included in this review: 35 on comorbidity and 2 on frailty. Of the 35 studies, 13 with comparable methodology were eligible for a meta-analysis. Compared to CRC patients without comorbidity, those with mild/moderate and severe comorbidity had, respectively, a higher risk of 30-day (OR = 1.71; 95% confidence interval (CI): 1.26–2.31 and OR = 2.62; 95% CI: 1.97–3.47), overall (HR = 1.41; 95% CI: 1.23–1.62 and HR = 2.03; 95% CI: 1.76–2.34), and CRC-specific mortality (HR = 1.06; 95% CI: 1.02–1.10 and HR = 1.14; 95% CI: 1.04–1.23). Frail CRC patients showed higher overall mortality than non-frail patients (HR_range: 2.60–3.39).
Comorbidity and frailty are strong prognostic factors of survival in CRC patients apart from the commonly considered sociodemographic and tumor characteristics. Comprehensive geriatric assessment might help to optimize care of CRC patients, by improving early identification and management of comorbidities and geriatric syndromes.
Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review
2018, Journal of Geriatric Oncology
Treatment of metastatic colorectal cancer (mCRC) has been modified since the launching of targeted therapies. Colorectal cancer (CRC) is common in elderly patients; their representation in randomized controlled trials (RCTs) is thus crucial. This study aimed to evaluate and quantify the inclusion of elderly/frail patients in RCTs of targeted therapies in mCRC.
A systematic review using Medline, Scopus, Cochrane Database and ISI Web of Science was performed to identify all phase II/III RCTs of bevacizumab, cetuximab, panitumumab, regorafenib and aflibercept in mCRC until January 2015. Two reviewers independently performed studies selection, and data extraction. The protocol was registered in Prospero (CRD42015016163).
Among 1,369, identified publications, 54 RCTs were selected. Nine RCTs (17%) excluded elderly patients; median age of the included population was < 65 years old in 50 RCTs (93%). Twenty RCTs (37%) excluded frail patients, and many RCTs excluded patients with uncontrolled hypertension or heart failure, patients treated with specific drugs (mainly anticoagulants), and patients with inadequate creatinine clearance.
Elderly/frail patients are underrepresented in RCTs studying targeted therapies in mCRC, and those elderly patients included in RCTs do not reflect well the general elderly population with mCRC because of the exclusion criteria. RCTs results concerning targeted therapies can be inferred only to relatively healthy elderly subjects.
Global geriatric oncology: Achievements and challenges
2017, Journal of Geriatric Oncology
Citation Excerpt :
Geriatric oncology research is an important priority of the COSA group [46,47]. Many other centers around the country have also conducted research in older adults with cancer with a particular focus on colorectal cancer [48–50], supportive care [51], geriatric assessment [44,46], and polypharmacy [52,53]. In the absence of a formal geriatric oncology training program, a small number of physicians have undertaken training in both geriatrics and medical oncology.
The aging of the population is a global challenge. The number of older adults is rapidly growing, leading to an increase in the prevalence of noncommunicable diseases associated with aging, such as cancer. Worldwide, older adults account for approximately half of all cancer cases, and this proportion is projected to increase globally. Furthermore, the majority of older adults live in less developed regions, where health systems are generally ill-equipped to provide care for complex chronic conditions. Worldwide, there is paucity of geriatric training, and most of the oncology workforce lacks the skills and knowledge to provide comprehensive care for older patients. Various initiatives aimed at providing adequate clinical care for older adults, increasing the geriatric skills and knowledge of healthcare professionals, and developing geriatric oncology research, have been successfully implemented. However, most developments in geriatric oncology have taken place in high-income countries, and there are still large inequalities in the availability of clinical, educational, and research initiatives across different regions of the world. This article provides an overview of geriatric oncology initiatives in Asia, Europe, Australia and New Zealand, Latin America, and the United States and Canada. Understanding the achievements and challenges of geriatric oncology around the world, and fostering international collaboration in research and training are essential for improving the care of all older adults with cancer.

View all citing articles on Scopus

^☆: Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology, May 31 – June 4, 2013, Chicago, IL.

¹: S.P. and H.W. contributed equally to this work.

View full text

Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia☆

Abstract

Objectives

Materials and Methods

Results

Conclusion

Introduction

Section snippets

Materials and Methods

Statistical Analysis

Patient Characteristics

Discussion

Conclusion

Funding

Disclosures and Conflict of Interest Statements

Author Contributions

Acknowledgements

Lancet

Lancet Oncol

J Chronic Dis

Lancet

Lancet

Lancet Oncol

Ann Oncol

GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]

Cancer in Australia: an overview, 2012

Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials

J Clin Oncol