A Phase II Trial of Older Adults with Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology

Abstract

Introduction.

Phase-II clinical trials including geriatric assessment (GA) measures are critical for improving the evidence base for older adults with cancer. We assessed the efficacy and tolerability of nab-Paclitaxel in older adults with metastatic breast cancer (MBC).

Patients and Methods.

Patients aged ≥ 65 with MBC and ≤1 previous line of chemotherapy received 100 mg of nab-Paclitaxel on days 1, 8, and 15 of a 28-day cycle. A GA was completed pre-chemotherapy and a validated chemotherapy toxicity risk score was calculated. Relationships between tolerability (number of courses, hospitalizations, dose reductions, and toxicity) and risk score were assessed using general linear models, Student’s t-tests, and Fisher’s test. Response rate and progression free survival (PFS) were evaluated using the Kaplan Meier method.

Results.

Forty patients (mean age 73; range 65–87) were included. Median number of cycles was six, 75% (n=30) of patients had ≥ one dose hold, and 50% (n=20) had ≥ one dose reduction. Fifty-eight percent (n=23) had treatment-related ≥ G3 toxicities, and 30% (n=12) were hospitalized due to toxicity. Thirty-five percent (n=14) responded, and median PFS was 6.5 months (95% CI 5.5-undefined). Patients with intermediate/high toxicity risk scores had higher risk of Grade ≥ 3 toxicity than those with low risk scores (OR 5.8, 95% CI 1.3–33.1, p=0.01). A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations.

Conclusions.

Among older adults with MBC receiving weekly nab-Paclitaxel, more than half experienced Grade 3 ≥ chemotherapy toxicity. However, a GA-based risk score could predict treatment tolerability.

Microabstract:

Nab-Paclitaxel may be an attractive therapy for older adults because of its efficacy, the infrequency of allergic reactions, and the lack of need for steroid pre-medications. We evaluated the tolerability and efficacy of nab-Paclitaxel in older adults with metastatic breast cancer, as well as the relationship between a geriatric assessment-based toxicity risk score and chemotherapy toxicity, dose reductions, dose delays, and hospitalizations. Patients with intermediate/high toxicity risk scores had higher risk of Grade ≥ 3 toxicity than those with low risk scores, and a higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations. A geriatric assessment-based risk score can help weigh the risks and benefits of chemotherapy in older adults, and should be incorporated into future trials testing new therapies in this population.

INTRODUCTION

Breast cancer is a disease associated with aging,¹ and almost half of breast cancer diagnoses occur in women age 65 and older.² However, older adults with breast cancer have been underrepresented in registration clinical trials that inform the recommended drug dosing and expected toxicity profiles, which is included within the package insert.^3,4 Furthermore, little is known about whether older adults included in clinical trials are representative of the general population, since geriatric assessment measures are not included.⁵ In order to improve the evidence base for treatment of older adults with cancer, the Institute of Medicine (IOM), the American Society for Clinical Oncology (ASCO), and the Cancer and Aging Research Group (CARG)⁶ have identified phase II clinical trials including geriatric assessment measures as a critical component to improve the evidence base for treating older adults with cancer.^7,8

A recent systematic review identified only 16 phase II trials focusing on older patients treated with chemotherapy for metastatic breast cancer published between 2001 and 2014.⁹ Yet, most of these studies did not include geriatric-specific evaluations, and patients were enrolled based on chronologic age alone. Factors besides chronologic age may affect treatment tolerance in older patients, and a more detailed evaluation is warranted.¹⁰ This evaluation is known as the geriatric assessment, and it measures a patient’s functional status, comorbidities, cognition, nutritional status, social support, and psychological state.¹¹ There is an abundance of information demonstrating that GA detects general health care problems in older patients with cancer that routinely are under-recognized in clinical oncology care.¹² Furthermore, in older patients with cancer, the geriatric assessment has been shown to predict both survival^13–17 and severe chemotherapy toxicity.^18–22

`Current guidelines list weekly taxanes among the preferred options for treating older adults with metastatic breast cancer.²³ Nanoparticle albumin-bound (nab) paclitaxel has proven to be an efficacious and safe alternative to solvent-based taxanes (such as paclitaxel and docetaxel), since it requires no premedication and has a lower rate of hypersensitivity reactions.²⁴ Although retrospective studies have shown that nab-paclitaxel appears to be safe in older adults,²⁵ its clinical benefit and tolerability have not been prospectively assessed.

In this study, we evaluated the efficacy and the tolerability of weekly nab-paclitaxel in older adults with metastatic breast cancer. Furthermore, we explored the use of a previously developed and validated geriatric assessment-based risk score (Cancer and Aging Research Group [CARG] Chemotherapy Toxicity Calculator)^18,19 to predict the need for dose reductions, dose delays, hospitalizations, and/or Grade 3–5 chemotherapy toxicity attributed to treatment.

MATERIALS AND METHODS

Study Design and Objectives

This was a phase-II, single-arm, open-label, clinical trial of nab-paclitaxel in older adults with metastatic breast cancer conducted at City of Hope National Medical Center (COH) in Duarte, CA and Ohio State University Cancer Center in Columbus, OH. The primary objective was to assess tolerability, defined as the presence of Grade 2–5 chemotherapy toxicity, and dose reductions, delays or interruptions. Secondary objective included estimation of overall response rate (ORR, defined as the sum of complete [CR] and partial response [PR]), median progression free survival [PFS], median overall survival (OS), the use of a cancer-specific geriatric assessment to describe the study population, and the CARG chemotherapy toxicity calculator to predict the need for dose reduction, dose delays, or occurrence of Grade 3–5 chemotherapy toxicity. This study was approved by the City of Hope National Medical Center Institutional Review Board and all study participants provided written informed consent. The study was registered at clinicaltrials.gov (NCT01463072).

Eligibility

Patients were eligible if they were age ≥ 65 years, had a diagnosis of metastatic breast cancer with any hormone receptor (HR) or HER-2 status, and were able to provide informed consent. Patients with 0–1 previous lines of chemotherapy for metastatic disease were eligible. Additional inclusion criteria were: Karnofsky Performance Status (KPS) score ≥ 70%; resolution of Grade ≥ 2 toxicity from prior therapy (other than alopecia); peripheral neuropathy Grade ≤ 1; neutrophil count ≥ 1,500/mm3; platelets ≥ 100,000cells/mm3; Hb ≥ 9.0g/dl; and adequate hepatic and renal function. Patients were excluded if they were receiving any other investigational agents; had untreated or symptomatic central nervous system metastases; had a known allergy to paclitaxel; had received a taxane for adjuvant therapy or metastatic disease in the last 12 months; or had any serious uncontrolled infection.

Treatment plan

Baseline evaluations included a complete medical history and physical examination. Blood was obtained for complete blood cell counts (CBC) and metabolic panels. A contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis was conducted prior to treatment initiation.

Nab-Paclitaxel was administered on an outpatient basis at a dose of 100 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle. Patients were followed for adverse events throughout the study period and these were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.²⁶ Hospitalizations related to chemotherapy-related toxicity were recorded.

Drug delays were allowed for patients with Grade ≥ 2 neutropenia, platelet count <100,000/mm³, and hemoglobin ≤ 9.0g/dL. In instances of neutropenia, therapy was resumed at the same dose with the support of granulocyte-colony stimulating factor (G-CSF). Nab-paclitaxel was held in cases of Grade 2–3 peripheral neuropathy and restarted at a dose of 80mg/m² after neuropathy became Grade ≤1.Patients with other Grade ≥ 3 toxicities, as well as those with Grade 1–2 toxicities deemed significant by the treating physician, could also have a dose delay or reduction at physician discretion.

Response Assessment

CT scans of the chest, abdomen, and pelvis were performed every 2 cycles or sooner if clinically indicated. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.²⁷

Geriatric Assessment and Chemotherapy Toxicity Risk Score

A geriatric assessment was completed prior to study initiation, prior to the third cycle of therapy, and at study termination. This tool^28,29 included an evaluation of functional status (Activities of Daily Living [ADL]³⁰ and Instrumental Activities of Daily Living [IADL]);³¹ physical function (Timed Up and Go test),³² number of falls, ³³ comorbidities [OARS comorbidity scale]);³⁴ number of medications; cognition (Blessed Orientation-Memory-Concentration test);³⁵ psychological state (Mental Health Inventory-17);³⁰ social support (Medical Outcomes Study Social Support survey);³⁰ social functioning (Medical Outcomes Study Social Activity Limitations Measure);³⁰ and nutritional status (BMI and self-reported weight loss).

The CARG chemotherapy toxicity risk score was calculated for each patient at baseline prior to the first cycle of nab-paclitaxel.^18,19 The variables included in the prediction model and scoring algorithms, as well as risk of toxicity by score, are shown in Figure 1. Patients were categorized as being at low, intermediate, or high risk of chemotherapy toxicity according to their risk score.

Figure 1:

a) Prediction Model and Scoring Algorithm for Chemotherapy Toxicity b) Percent Risk of Toxicity by Score

Statistical Analysis

Rates and associated 95% confidence limits were estimated for 1) Grade ≥ 2 chemotherapy toxicity; 2) dose reductions, delays, and holds; 3) hospitalizations; and 4) ORR. Median PFS and OS were estimated using the method of Kaplan and Meier. Descriptive statistics for patient demographics, number of cycles received, tumor characteristics, and geriatric assessment results are provided.

The baseline chemotherapy toxicity risk (represented by the rate of chemotherapy toxicity risk) was skewed to the right, indicating a log transformation, so we used a log₂ transformation in order to analyze changes based on doubling of the rate of toxicity risk. We compared the log₂ toxicity risk for participants who had at least one dose reduction, dose hold, or hospitalization to those that did not using a two-tailed, two-sample Student’s T-test assuming unequal variances. Fisher’s exact test was used to compare the rates of Grade 3 and above toxicities across CARG toxicity risk categories, and linear regression was used to determine if the toxicity risk predicted the number of courses completed.

RESULTS

Patient Characteristics

Forty patients (mean age 73 [range 65–87]) were enrolled between June 2012 and January 2016. Thirty eight (95%) enrolled at COH and 2 (5%) at Ohio State. Table 1 displays the baseline characteristics and geriatric assessment results of the study patients. Forty percent (n=16) were ≥75 years of age. Most participants were female (95%, n= 38), white (73%, n=29), non-Hispanic (83%, n=33). Seventy-five percent (n=30) had HR-positive tumors. Fifty-eight percent (n=23) received nab-paclitaxel as their first-line of chemotherapy for metastatic disease.

Table 1:

Patient Demographic and Geriatric Assessment Results

Characteristic	Total (N=40)
Age, years
65–69	15	(38%)
70–74	9	(23%)
≥ 75	16	(40%)
Sex
Male	2	(5%)
Female	38	(95%)
Race
Asian	6	(15%)
Black	4	(10%)
Caucasian	29	(73%)
Other	1	(3%)
Receptor Status
HR-positive	30	(75%)
Triple negative	10	(25%)
Treatment Line
First line	23	(58%)
Second line	17	(43%)
Instrumental Activities of Daily Living (IADL)
Median (range)	13	(6–14)
Dependence in at least one IADL	24	(60%)
Activities of Daily Living (ADL) (0–100)
Mean (SD)	53.7	(27.94)
Dependence in ADL	26	(65%)
≥ 1 fall in the previous 6 months	9	(22.5%)
≥ 6% weight loss in the previous 6 months	10	(25%)
Comorbidities
Median (range)	3	(0–6)
Abnormal Cognitive Screening	3	(7.5%)
Mental Health Inventory (0–100)
Median (SD)	74.1	(16.51)
Social Support Survey (0–100)
Mean (SD)	82.7	(18.11)
Hemoglobin Level
Mean (SD)	11.8	(1.61)
< 11g/dL (male), < 10g/dL (female)	6	(15%)
Creatinine Clearance < 34ml/min (Jeliffe)	3	(7.5%)

Abbreviations: SD: standard deviation

Tolerability

The median number of completed cycles was 6 (range 0–33). Seventy-five percent (n=30, 95% CI 59–87%) had ≥ 1 dose hold and 50% (n=20, 95% CI 34–66%) had ≥ 1 dose reduction. Ten percent of participants (n=4, 95% CI 3–24%) experienced delays in ≥ 1 cycle.

Ninety percent (n=36, 95% CI 76–97%) had Grade 2 or above toxicities that were attributable to treatment. Fifty eight percent (n=23) had Grade 3 or above toxicities that were attributable to treatment. Only one participant had a Grade 4 toxic event. Ten percent (n=4) experienced Grade ≥ 2 peripheral sensory neuropathy (5% G2, n=2; 5% G3, n=2). Thirty percent of the patients (n=12, 95% CI 17–47%) were hospitalized due to chemotherapy toxicity during the study period, and 28% (n=11, 95% CI 15–44%) stopped treatment due to treatment-related toxicity. Table 2 summarizes the most commonly observed adverse events.

Table 2:

Toxicities Experienced

Adverse Event Category	Grade 2	Grade 3	Grade 4
Non-hematologic Toxicities *	18 (45%)	14 (35%)	0 (0%)
Heart Failure	0 (0%)	1 (3%)	0 (0%)
Diarrhea	3 (8%)	3 (8%)	0 (0%)
Mucositis oral	0 (0%)	1 (3%)	0 (0%)
Nausea	1 (3%)	3 (8%)	0 (0%)
Vomiting	0 (0%)	4 (10%)	0 (0%)
Fatigue	20 (50%)	2 (5%)	0 (0%)
Pain	2 (5%)	0 (0%)	0 (0%)
Allergic Reaction	3 (8%)	0 (0%)	0 (0%)
Infections and infestations Other, specify	2 (5%)	0(0%)	0 (0%)
Upper respiratory infection	6 (15%)	1 (3%)	0 (0%)
Urinary tract infection	4 (10%)	1 (3%)	0 (0%)
Nail infection	2 (5%)	0 (0%)	0 (0%)
Alanine aminotransferase increased	0 (0%)	1 (3%)	0 (0%)
Aspartate aminotransferase increased	0 (0%)	2 (5%)	0 (0%)
Dehydration	4 (10%)	2 (5%)	0 (0%)
Hypocalcemia	1 (3%)	1 (3%)	0 (0%)
Hypokalemia	2 (5%)	1 (3%)	0 (0%)
Hyponatremia	0 (0%)	1 (3%)	0 (0%)
Muscle weakness upper limb	0 (0%)	1 (3%)	0 (0%)
Encephalopathy	0 (0%)	1 (3%)	0 (0%)
Peripheral sensory neuropathy	2 (5%)	2 (5%)	0 (0%)
Stroke	0 (0%)	1 (3%)	0 (0%)
Cough	2 (5%)	0 0%)	0 (0%)
Dyspnea	2 (5%)	1 (3%)	0 (0%)
Hypoxia	1 (3%)	1 (3%)	0 (0%)
Hypotension	3 (8%)	0 (0%)	0 (0%)
Thromboembolic event	1 (3%)	1 (3%)	0 (0%)
Hematologic toxicities *	18 (45%)	12 (30%)	1 (3%)
Anemia	13 (33%)	7 (18%)	0 (0%)
Lymphocyte count decreased	6 (15%)	1 (3%)	0 (0%)
Neutrophil count decreased	13 (33%)	3 (8%)	1 (3%)
White blood cell decreased	21 (53%)	4 (10%)	0 (0%)

^*Per Common Terminology Criteria for Adverse Events version 4.0; all Grade 3–4 toxicities or Grade 2 experienced by more than one participant.

Thirty-five percent of the patients (n=14) were responders (95% CI 21–52%), with 3% CR (n=1) and 33% PR (n=13). Forty percent of the patients (n=16) achieved stable disease; 10% (n=4) had disease progression; and 15% (n=6) came off of treatment before 2 cycles. The median PFS was 6.5 months, (95% CI 5.5, undefined) and median overall survival (OS) was 21.2 months (95% CI 14.6, undefined).

Geriatric Assessment and Chemotherapy Risk Score

The results of the geriatric assessment prior to treatment are shown in Table 1. Sixty percent of the patients (n= 24) required assistance in at least one IADL. Twenty-three percent (n= 9) reported at least one fall in the previous 6 months, 25% had involuntary weight loss and 3% had an abnormal cognitive screening. Half of the patients had ≥ 3 comorbidities. The mean score on the MHI-17 questionnaire (scores 0–100) was 74 (SD 16.5) and 35% (n=14) reported poor emotional support. Using the CARG chemotherapy toxicity risk score, 53% of the patients (n=21) were categorized at low, 38% (n=15) at intermediate and 10% (n=4) at high risk of Grade ≥ 3 chemotherapy toxicity (Figure 2).

Figure 2:

Number of participants with Grade 3–4 National Cancer Institute Common Terminology Criteria for Adverse Events by Cancer and Aging Research Group (CARG) risk category

Chemotherapy Risk Score and Tolerability

Since only 4 patients were in the high-risk category using the chemotherapy toxicity risk calculator, high and intermediate risk categories were combined. Patients with an intermediate or high toxicity risk had a higher risk of Grade ≥ 3 chemotherapy toxicities than those with a low toxicity risk (OR 5.8, 95% CI 1.3–33.1, p=0.01) (Figure 2). Patients had a dose reduction due to chemotherapy toxicity were found to have a significantly higher mean toxicity risk than those who did not required a dose reduction (ratio of the group means=1.38, 95% CI 1.04, 1.80, p=0.02) (Figure 3a).

Figure 3:

Association between toxicity risk and a) dose reductions, and b) hospitalizations. The blue dot represents the mean; red dots represent individual participant results. The line within the box represents the median, the upper and lower ends of the boxes represent the 25^th and 75^th percentiles and the ends of the whiskers represent the individual result within 1.5 times the interquartile range.

Patients who were hospitalized due to chemotherapy toxicity had a significantly higher mean toxicity risk than those who were not hospitalized (ratio of the group means=1.5, 95% CI 1.13–2.00, p < 0.01) (Figure 3b). The toxicity risk was a significant predictor of the number of completed courses. A doubling in rate of toxicity risk resulted in a reduction in the number of completed courses by 4.5 (se=1.4, p<0.01) (Figure 4).

Figure 4:

Association between toxicity risk score and number of courses completed

DISCUSSION

Among older adults with metastatic breast cancer receiving weekly nab-paclitaxel, more than half experienced Grade 3 or higher chemotherapy toxicity. However, a geriatric assessment-based risk score was able to predict treatment tolerability, and patients with higher toxicity risk were more likely to experience Grade ≥ 3 toxicity, to need dose reductions, to receive fewer treatment cycles, and to be hospitalized than those with lower risk scores.

Determining the best treatment strategy for an older patient with metastatic breast cancer is a difficult task for clinicians. Therapeutic decisions are often based on chronological age alone, and older patients are less likely to receive standard, evidence-based care.³⁶ One reason for this is the underrepresentation of older adults (particularly those who are vulnerable and/or frail) in therapeutic clinical trials.⁶ Therefore, understanding the tolerability and efficacy of chemotherapy in older adults, including those who are vulnerable and/or frail, is one of the highest priorities in geriatric oncology.⁸

This study evaluated a widely used agent, nab-paclitaxel, in a population of older adults with a significant proportion of functional deficits and comorbidities. Nab-paclitaxel could represent a less toxic alternative to solvent-based taxanes in vulnerable older patients due to the lower incidence of allergic reactions and because no steroid premedication is needed.^24,25 Furthermore, we have previously demonstrated that pharmacodynamic variables of nab-paclitaxel are not influenced by chronological age.³⁷ In the randomized controlled trial (RCT) leading to approval of nab-paclitaxel, only 13% (n=62) of the patients were older than 65,³⁸ and only 32 patients age ≥ 70 received nab-paclitaxel in a recently published RCT comparing various treatments among 799 patients with metastatic breast cancer.³⁹

The proportion of patients with severe toxicity in our study was different than previously reported in a pooled analysis of patients older than 65 treated with nab-paclitaxel, with fewer cases of Grade 3 neutropenia and sensory neuropathy in our cohort. ²⁵ The lower incidence of neuropathy may be related to the very strict criteria for dose hold and dose reduction in our study compared with previous trials. Nab-paclitaxel was held in patients with Grade 2 neuropathy and restarted at an 80% dose, while in previous trials, patients with Grade 2 neuropathy have undergone dose reduction without dose holds.³⁹ In contrast, the ORR of 35% and the PFS of 6.5 months found in our study population were similar to those previously reported in a phase II trial utilizing a similar dosage of weekly nab-paclitaxel (45% and 7.5, months respectively).⁴⁰ Of note, in that trial the mean age of the participants was 53.9 years, and only 17% were older than 65.

We have previously shown that a geriatric assessment-based risk score can be used to predict severe chemotherapy toxicity in older patients across tumor types, and that the tool outperforms usual oncology assessments such as KPS.^18,19 In the present study, we evaluated the performance of our risk score to predict the tolerability of nab-paclitaxel in older patients with metastatic breast cancer. Our results show that in this population, the risk score can identify patients who are at a high risk of experiencing severe toxicity or hospitalization, as well as those less likely to complete the planned treatment. Thus, this tool can potentially be integrated into randomized controlled trials in order to allocate patients to different treatment strategies, thus allowing for the enrollment of vulnerable and/or frail patients. A similar strategy was utilized in the recently published ESOGIA trial in lung cancer,⁴¹ in which patients were assigned to different chemotherapy doses or supportive care depending on the results of a geriatric assessment. This study showed that although geriatric-assessment based treatment allocation for chemotherapy did not improve PFS or OS over usual care, it resulted in less all-grade toxicity (86% vs. 93%, p = 0.015), higher quality of life scores, and fewer treatment failures without compromising survival.^{40, 42}

This study has limitations. First, although we were able to show that the chemotherapy risk score predicted treatment tolerability, we can’t tell whether treatment modifications or dose reductions in patients with a high risk score will lead to less toxicity or different outcomes. However, this phase II trial sets the stage for randomized controlled trials comparing usual decision-making criteria (such as chronological age or simple performance status measures) to treatment allocation utilizing the chemotherapy toxicity risk score. Second, our patients were recruited at a comprehensive cancer center, and they may not be representative of patients seen in other settings. Nevertheless, it is important to emphasize that our cohort included a significant proportion of patients who had markers of vulnerability: 60% needed assistance in instrumental activities of daily living, 50% had 3 or more comorbidities, 40% had involuntary weight loss, and 23% had falls in the last 6 months. Third, most of our patients were non-Hispanic white, and thus the applicability of our results to other racial and ethnic groups with differing sociodemographic characteristics is limited.

Despite these limitations, our study has several strengths. It addresses a key research priority described by the Institute of Medicine, the American Society of Clinical Oncology, and the Cancer and Aging Research Group by expanding the knowledge base regarding a commonly utilized chemotherapy agent in older adults with metastatic breast cancer. Furthermore, we showed that incorporating a geriatric assessment and a chemotherapy toxicity risk score could identify patients who were less likely to tolerate treatment. This, in turn, could help clinicians and their older patients weigh the risks and benefits of treatment, ultimately personalizing cancer care.

Clinical Practice Points:

• Few clinical trials exploring the use of chemotherapy in metastatic breast cancer have focused on older patients.

• Nab-paclitaxel may be an attractive option in older adults with metastatic breast cancer since it requires no premedication and has lower rate of hypersensitivity reactions.

• In this phase II trial we evaluated the tolerability and efficacy of nab-paclitaxel among women aged 65 years and older with metastatic breast cancer.

• All patients underwent a cancer-specific geriatric assessment, and a previously validated chemotherapy toxicity risk score was calculated for each patient.

  • We explored the use of this risk score to predict chemotherapy-related toxicity, as well as the need for dose reductions, delays, and hospitalizations.
• Forty older adults were included in the study.

  • 58% had Grade 3 or higher toxicities, and 30% were hospitalized due to toxicity.
  • 35% had an objective response to treatment.
  • Median progression free survival was 6.5 months, and median overall survival 21.2 months.
  • Patients with intermediate/high toxicity risk scores had higher risk of Grade ≥ 3 toxicity than those with low risk scores.
  • A higher mean risk score was associated with higher likelihood of dose reductions and hospitalizations.

• A geriatric assessment-based chemotherapy toxicity risk score could identify older patients who are less likely to tolerate treatment.

• This could help clinicians and their older patients weigh the risks and benefits of treatment, leading to improvements in personalized cancer care.

Abbreviations:

IOM

Institute of Medicine

ASCO

American Society of Clinical Oncology

CARG

Cancer and Aging Research Group

nab

nanoparticle albumin-bound

GA

geriatric assessment

COH

City of Hope

ORR

overall response rate

CR

complete response

PR

partial response

PFS

progression free survival

OS

overall survival

HR

hormone receptor

KPS

Karnofsky Performance Status

Hb

hemoglobin

CBC

complete blood cell counts

CT

computed tomography

G-CSF

granulocyte-colony stimulating factor

RECIST

Response Evaluation Criteria in Solid Tumors

ADL

activities of daily living

IADL

instrumental activities of daily living

OARS

Older Americans Resources and Services

CI

confidence interval

RCT

randomized controlled trial