Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR = 1.56 [95%CI: 1.12-2.16]), and ipilimumab-related (RR = 2.18 [95% CI: 1.45-3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.

Real-world comparative effectiveness of second-line ipilimumab for metastatic melanoma: a population-based cohort study in Ontario, Canada.

BACKGROUND: For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment's real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments). METHODS: We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting (IPTW). RESULTS: We identified 329 patients with metastatic melanoma (MM) who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27-41%), 20.6% (15-27%), and 15.2% (9.6-21%) for ipilimumab and 17.1% (11-23%), 7.1% (2.9-11%), and 4.7% (1.2-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR = 0.62; 95% CI: 0.49-0.78; p < 0.0001). CONCLUSIONS: This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Characterization of Post-Thrombotic Syndrome in Children with Cardiac Disease.

OBJECTIVE: To assess the validity of existing clinical scales assessing the presence of physical and functional abnormalities for diagnosing post-thrombotic syndrome (PTS) in children, including specific evaluation of use in children with congenital heart disease (CHD). STUDY DESIGN: One hundred children aged >2 years (average age, 6 years), including 33 with CHD and previously proven extremity deep vein thrombosis (DVT), 37 with CHD and no previous DVT, and 30 healthy siblings, were blindly assessed for PTS using the modified Villalta Scale (MVS). All patients aged <6 years underwent neurodevelopmental testing and an age-appropriate quality of life assessment. RESULTS: The MVS identified mild PTS in 20 children and moderate PTS in 1 child (including 14 of 33 [42%] in the CHD/DVT group, 5 of 37 [14%] in the CHD/no DVT group, and 2 of 30 controls [7%]). The diagnosis of PTS was confirmed clinically in 14 patients, all of whom had previous thrombosis and 1 of whom was MVS-negative. MVS had an accuracy of 91% and performed reasonably well as a screening tool but poorly as a diagnostic tool. MVS reliability was acceptable. Children with PTS had similar quality of life as those without PTS but had higher rates of neurodevelopmental delays in gross motor skills (70% vs 24%; P = .02) and problem-solving indicators (60% vs 15%; P = .008). CONCLUSIONS: Using the MVS scale for PTS screening in children with CHD is feasible and reliable, and the scale has good correlation with a clinical diagnosis of PTS despite a high prevalence of false-positive findings. Further research is needed to determine the clinical relevance of PTS in this population.

Bridging research gaps in geriatric oncology: unraveling the potential of pragmatic clinical trials.

PURPOSE OF REVIEW: This review examines the role of pragmatic clinical trials (PCTs) in addressing the underrepresentation of older adults with cancer (OAC) in clinical trials. Focusing on real-world evidence (RWE), it aims to provide a comprehensive overview of PCT utilization, emphasizing their potential to enhance treatment decisions and patient outcomes. Existing knowledge gaps in PCT implementation are also discussed. RECENT FINDINGS: PCTs are identified as effective tools to include OACs with comorbidities and complex conditions in research, bridging the representation gap. Despite their proven value in healthcare provision, their application in OAC contexts remains limited, hindering comprehensive understanding and inclusivity in clinical trials. SUMMARY: While randomized controlled trials (RCTs) are considered the gold standard in oncology research, OACs have historically been excluded, perpetuating underrepresentation. Furthermore, even in current oncology clinical development trials, this demographic continues to be underrepresented. PCTs offer a valuable avenue for the identification and evaluation of therapies within authentic RW contexts, encompassing various healthcare settings, such as hospitals, clinics, and physician practices. RCTs and PCTs complement one another, and the utilization of PCTs has the potential to inform clinical decision-making across the OACs entire treatment trajectory.

Immunotherapy for older patients with cancer.

PURPOSE OF THE REVIEW: The aim of this review is to describe the clinical use and tolerability of immune checkpoint inhibitors in older adults with solid tumors, where there is an abundance of evidence with recent updates including subgroups of older patients. RECENT FINDINGS: Studies with updated analyses and subgroups of older patients show that in general older patients benefit as well as younger patients and tolerate immunotherapy very well. However, in some instances of combination therapies which may expose patients to more toxicity, the benefits are reduced, and careful selection of older patients, including adjunctive assessments such as geriatric assessment, can help to identify the appropriate treatment for an individual patient. SUMMARY: Older adults remain underrepresented in clinical trials, including those involving immunotherapy. Therefore, efforts must be made to include more older patients in trials and to assess real-world evidence to inform decision-making.

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

BACKGROUND: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM. METHODS: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5-year time horizon, censor-adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost-effectiveness ratios (ICERs) in life-years gained (LYGs) and quality-adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. RESULTS: In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. CONCLUSION: Despite its clinical benefit, ipilimumab as second-line monotherapy for MM patients is not cost-effective in the real world as projected by HTA under conventional willingness-to-pay thresholds.

Implementing geriatric assessment and management for older Canadians with cancer: Adherence to and satisfaction with the intervention, results of the 5C study.

INTRODUCTION: Geriatric assessment and management (GAM) is recommended by professional organizations and recently several randomized controlled trials (RCTs) demonstrated benefits in multiple health outcomes. GAM typically leads to one or more recommendations for the older adult on how to optimize their health. However, little is known about how well recommendations are adhered to. Understanding these issues is vital to designing GAM trials and clinical programs. Therefore, the aim of this study was to examine the number of GAM recommendations made and adherence to and satisfaction with the intervention in a multicentre RCT of GAM for older adults with cancer. MATERIALS AND METHODS: The 5C study was a two-group parallel RCT conducted in eight hospitals across Canada. Each centre kept a detailed recruitment and retention log. The intervention teams documented adherence to their recommendations. Medical records were also reviewed to assess which recommendations were adhered to. Twenty-three semi-structured interviews were conducted with 12 members of the intervention teams and 11 oncology team members to assess implementation of the study and the intervention. RESULTS: Of the 350 participants who were enrolled, 173 were randomized to the intervention arm. Median number of recommendations was seven. Mean adherence to recommendations based on the GAM was 69%, but it varied by type of recommendation, ranging from 98% for laboratory tests to 28% for psychosocial/psychiatry oncology referrals. There was no difference in the number of recommendations or non-adherence to recommendations by sex, level of frailty, or functional status. Oncologists and intervention team members were satisfied with the study implementation and intervention delivery. DISCUSSION: Adherence to recommendations was variable. Adherence to laboratory investigations and further imaging were generally high but much lower for recommendations regarding psychosocial support. Further collaborative work with older adults with cancer is needed to understand how to optimize the intervention to be consistent with patient goals, priorities, and values to ensure maximal impact on health outcomes.

Impact of Geriatric Assessment and Management on Quality of Life, Unplanned Hospitalizations, Toxicity, and Survival for Older Adults With Cancer: The Randomized 5C Trial.

PURPOSE: American Society of Clinical Oncology recommends that older adults with cancer being considered for chemotherapy receive geriatric assessment (GA) and management (GAM), but few randomized controlled trials have examined its impact on quality of life (QOL). PATIENTS AND METHODS: The 5C study was a two-group parallel 1:1 single-blind multicenter randomized controlled trial of GAM for 6 months versus usual oncologic care. Eligible patients were age 70+ years, diagnosed with a solid tumor, lymphoma, or myeloma, referred for first-/second-line chemotherapy or immunotherapy or targeted therapy, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary outcome QOL was measured with the global health scale of the European Organisation for the Research and Treatment of Cancer QOL questionnaire and analyzed with a pattern mixture model using an intent-to-treat approach (at 6 and 12 months). Secondary outcomes included functional status, grade 3-5 treatment toxicity; health care use; satisfaction; cancer treatment plan modification; and overall survival. RESULTS: From March 2018 to March 2020, 350 participants were enrolled. Mean age was 76 years and 40.3% were female. Fifty-four percent started treatment with palliative intent. Eighty-one (23.1%) patients died. GAM did not improve QOL (global QOL of 4.4 points [95% CI, 0.9 to 8.0] favoring the control arm). There was also no difference in survival, change in treatment plan, unplanned hospitalization/emergency department visits, and treatment toxicity between groups. CONCLUSION: GAM did not improve QOL. Most intervention group participants received GA on or after treatment initiation per patient request. Considering recent completed trials, GA may have benefit if completed before treatment selection. The COVID-19 pandemic may have affected our QOL outcome and intervention delivery for some participants.

Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery.

BACKGROUND: Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. METHODS AND RESULTS: We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/10(9) cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. CONCLUSIONS: Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation.

OBJECTIVES: To describe the incidence of thrombotic complications across all 3 stages of single ventricle palliation and the association between thromboprophylaxis use and thrombotic risk. STUDY DESIGN: Two separate cross-sectional studies were performed that included 195 patients born between 2003-2008 and 162 patients who underwent Fontan after 2000. RESULTS: The incidence of thrombotic complications was 40% and 28% after initial palliation and superior cavopulmonary connection (SCPC), respectively; 5-year freedom from thrombotic complications after Fontan was 79%. Thromboprophylaxis was initiated for 70%, 46%, and 94% of patients after initial palliation, SCPC, and Fontan, respectively. Thromboprophylaxis with enoxaparin (vs no thromboprophylaxis) was associated with a reduction in risk of thrombotic complications after initial palliation (hazard ratio [HR] 0.5, P = .05) and SCPC (HR 0.2, P = .04). Thromboprophylaxis with warfarin was associated with a reduction in thrombotic complications after Fontan (HR 0.27, P = .05 vs acetylsalicylic acid; HR 0.18, P = .02 vs no thromboprophylaxis). Thrombotic complications were associated with increased mortality after initial palliation (HR 5.5, P < .001) and SCPC (HR 12.5, P < .001). Three patients experienced major bleeding complications without permanent sequelae (2 enoxaparin, 1 warfarin). CONCLUSIONS: Given the negative impact of thrombotic complications on survival, the low risk of serious bleeding complications, and the association between thromboprophylaxis and lowered thrombotic complication risk across all 3 palliative stages, routine use of thromboprophylaxis from the initial palliation to the early post-Fontan period in this population may be indicated.

The effect of age on the opportunity to receive cancer treatment.

INTRODUCTION: Older adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment. METHODS: Patients age 45-99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years. RESULTS: A total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45-64, 65-79, 80-89, and 90-99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84-0.89)], which decreased further among octogenarians [aOR 0.63 (0.59-0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26-1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45-64 year-olds, 99.4% in 65-79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients). CONCLUSION: Older patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients.

Predicting treatment toxicity in older adults with cancer.

PURPOSE OF REVIEW: To provide an overview of the recent advancements in predicting toxicity associated with cancer treatment in older patients. RECENT FINDINGS: Various screening tools and validated risk calculators have been shown to help predict toxicity from surgery and chemotherapy. Radiation therapy has been more challenging to select the appropriate tool to reliably predict patients at risk for toxicity and noncompliance. Ongoing work on electronic geriatric assessment tools is showing promise in making comprehensive assessment more feasible. SUMMARY: Selecting appropriate cancer therapy is particularly important in older patients, and validated tools have been developed to guide clinicians for surgery and chemotherapy; however, radiotherapy toxicity remains an area for further development, as does the uptake of existing tools into routine oncology practice.

Evaluation of a Multidisciplinary Immunotherapy Toxicity Monitoring Program for Patients Receiving Ipilimumab for Metastatic Melanoma.

PURPOSE: Ipilimumab is an effective treatment for melanoma; however, toxicity rates remain high. The objective of this study was to describe the rates of adverse events (AEs), emergency room (ER) visits, hospitalizations, and nursing resource utilization for patients enrolled in a nurse-led telephone toxicity monitoring program. METHODS: Patients received weekly telephone calls from nursing to review a toxicity checklist during ipilimumab treatment and for 8 weeks after completion. To evaluate this program, a single-center retrospective review was performed for patients treated between July 2012 and September 2017 with single agent ipilimumab for advanced melanoma. Data were collected up to 3 months post-ipilimumab. RESULTS: A total of 67 patients were included, with a mean (standard deviation) age of 61 (14.6) years. Thirty-three (49%) patients received four doses of ipilimumab, and 17 (25%) had one dose delay. The median (IQR) of any AEs reported per patient was 11 (8-17). There were 44 (66%) patients with AEs deemed to be definitely or probably related to ipilimumab, and of those, 3 (4%) experienced a grade 3 AE, whereas 4 (6%) experienced grade 4 AEs. Twenty patients (30%) had ER visits, and 31 (46%) were hospitalized during follow-up (9% ER visits and 6% hospitalizations were related to drug toxicity). CONCLUSION: Ipilimumab is associated with high rates of toxicity; however, a proactive nurse-led monitoring program was feasible and patients had low rates of grade 3-4 toxicity. Hospitalization rates and ER visits remained high; however, the minority of those were related to drug toxicity.

Gait Speed vs. VES-13: A Pilot Study Comparing Screening Tools to Determine the Need for a Comprehensive Geriatric Assessment in Senior Women with Breast Cancer.

BACKGROUND/OBJECTIVES: Patients aged 70 years and older may be suboptimally treated with cancer therapy because of the lack of clinical trial data in this population. The Comprehensive Geriatric Assessment can be time consuming, and access to geriatricians is limited. This study aims to determine whether gait speed (GS) analysis is equivalent to the widely accepted Vulnerable Elders Survey 13 (VES-13) in identifying vulnerable or frail patients in need of a Comprehensive Geriatric Assessment. METHODS: A pilot prospective cohort study was carried out at a tertiary cancer centre in Toronto, Canada, in a radiation oncology breast follow-up clinic. GS analysis and VES-13 were completed by each patient at the same clinic visit. GS of <1 meter/second (m/s) and VES-13 score ≥3 were considered abnormal. Sensitivity, specificity, positive and negative predictive values, and Kappa characteristic were calculated for GS compared with VES-13. RESULTS AND DISCUSSION: Twenty-nine participants aged 70 years and older with any stage of breast cancer were included. The GS was 67% sensitive and 95% specific for abnormal VES-13 scores. The GS had an 86% positive predictive value and 86% negative predictive value for abnormal scores on VES-13. Overall, the GS showed a substantial strength of agreement with the VES-13 (kappa 0.66, P < .0001). CONCLUSION: The GS analysis compared very well with VES-13 scores, and this may be a reasonable alternative to VES-13 screening. This pilot data warrant further study in a larger group of patients.

An update on treatment for post-menopausal metastatic breast cancer in elderly patients.

INTRODUCTION: Elderly patients make up a significant proportion of patients with metastatic breast cancer. With several options available in the metastatic setting for hormone positive breast cancer, these patients require an individualized approach to decision-making that considers multiple factors beyond performance status and chronologic age. AREAS COVERED: The authors review the literature on endocrine monotherapy and combinations for hormone positive metastatic breast cancer, with specific commentary on the efficacy and toxicity for elderly patients. The authors describe the role of comprehensive geriatric assessment (CGA) and highlight the considerations for the use of bone modifying agents, and HER2-targeted therapy for hormone positive/HER2+ patients. EXPERT OPINION: Evidence for elderly patients is largely based on subgroup analyses, which should be interpreted with caution. Nonetheless, elderly patients with metastatic hormone receptor positive breast cancer appear to derive similar benefit from treatments as younger patients. Similarly, for most drugs, these patients have no significant worsening of toxicity compared to younger patients. In addition to tumor biology, patient values and information from the CGA should be used to guide treatment decisions.

Use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in older patients with ER-positive HER2-negative breast cancer: Young International Society of Geriatric Oncology review paper.

The current standard of care for the management of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer has been redefined by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Although adults aged 65 years and older account for the majority of patients with breast cancer, limited data are available about the age-specific dosing, tolerability, and benefit of CDK4/6 inhibitors in this growing population. Older adults are under-represented in clinical trials and as a result, clinicians are forced to extrapolate from findings in younger and healthier patients when making treatment decisions for older patients. In this article, we review the limited age-specific evidence on the efficacy, toxicity, and quality of life (QoL) outcomes associated with the use of CDK4/6 inhibitors in older adults. We also describe ongoing trials evaluating CDK4/6 inhibitors in the older population and highlight that only a minority of adjuvant and metastatic trials of CDK4/6 inhibitors in the general breast cancer population includes geriatric assessments. Finally, we propose potential strategies to help guide decision making for fit and unfit older patients based on disease endocrine sensitivity, the need for rapid response and geriatric assessment.