American Society of Clinical Oncology (ASCO) 2012 Annual Meeting

Chicago, IL; May 1-5, 2012

Posters

Cognitive Assessment Recommended for All Older Patients With Cancer

A comprehensive geriatric assessment (CGA) should be performed in older cancer patients, and cancer treatment decisions should take into account the results of this assessment, according to Thibault De La Motte Rouge, MD, MSc, Salpetriere Hospital, Paris, lead investigator of a report evaluating the frequency of cognitive impairment in older cancer patients. The conclusion followed the finding that nearly one-fourth of older patients with cancer also had cognitive impairment. The group presented the study results in a poster session at the ASCO meeting.

De La Motte Rouge and colleagues explained that at their institution, a 1-hour oncogeriatric evaluation, which includes a CGA, is systematically performed for all elderly patients with cancer. The researchers reviewed data from all patients assessed between January 2009 and June 2011. This analysis included 378 patients (mean age, 84 years), of whom 87 (23%) had cognitive impairment. Of these patients, more than half (n=46) received the diagnosis of cognitive impairment after administration of the CGA. In the newly diagnosed patients, 70% (n=38) had Alzheimer’s disease, 25% (n=8) had mild cognitive impairment, and 5% (n=2) had vascular dementia.

Cancer treatment as planned was initiated in all but 12 patients (all had Alzheimer’s disease), for whom the decision was made to provide best supportive care based on a benefit versus risk oncologic assessment. Ten of the 12 patients had dependence in at least two activities of daily living (ADLs). Their median overall survival was 4.2 months.

Of the 72 patients for whom a specific anticancer therapy was proposed, chemotherapy was recommended in 62, hormonal therapy in nine, surgery in five, and radiotherapy in three. Treatment was initiated as recommended in all but four patients, for whom a best supportive care approach was taken following discussion with the patients and their relatives. For the overall cohort with cognitive impairment, median overall survival was 21.1 months in those younger than 80 years and 15.0 months in those aged 80 years and older.

“Following geriatric intervention, anticancer treatment remains feasible in the majority of patients with cognitive impairment,” said De La Motte Rouge.

ADLs outperformed performance status as a prognostic factor. Median overall survival was 29.3 months in patients with cognitive impairment who had an ADL score of 6, compared with 7.4 months in those with an ADL score of ≤5 (P=.0001). Those with altered nutritional status had a median overall survival of 13.2 months; whereas the median had not yet been reached in those with normal nutritional status (P=.0055). The median overall survival was 9.1 months in those with advanced disease; the median had not yet been reached in those with localized disease (P=.0061).

Patients with middle cerebral artery infarction had a better outcome than patients with other cognitive impairment diagnoses (P=.0008). In a multivariate analysis, an instrumental ADL score >5 and a Mini-Mental State Examination score of >24 were associated with a better prognosis.

“We recommend adapting treatment to patient comorbidities,” concluded De La Motte Rouge. “While taking into account comorbidities, the goal is still optimal treatment for patients with cognitive impairment.”—Wayne Kuznar

Greater Attention to Psychological Sequelae of Cancer is Warranted

Aging is associated with reduced anxiety in older adults with cancer, but symptoms of depression remain constant in this population, according to a secondary analysis of a prospective longitudinal study investigating chemotherapy toxicity in older adults with cancer. Data from the analysis were presented during a poster session at the ASCO meeting by researchers representing the Cancer and Aging Research Group, led by Talia Weiss, MA, research affiliate, Memorial Sloan-Kettering Cancer Center, New York.

“Within geriatric populations, while anxiety is not a pressing problem, depression and sadness are prevalent with serious consequences (eg, decreased adherence and longer hospital stays),” said Weiss. “Thus, clinicians should utilize screening tools with patients to detect depression, such as the Distress Thermometer as a rapid screen, the Hospital Anxiety and Depression Scale [HADS], or the Geriatric Depression Scale [GDS].”

The association between age, anxiety, and depression was assessed in a cohort of 500 older adults (mean age, 73 years; 56% women) who were enrolled initially into a study investigating chemotherapy toxicity. Of the participants, 61% had stage IV cancer, 22% had stage III, 12% had stage II, and 5% had stage I.

Anxiety and depression were measured by HADS, a 14-item self-report measure comprising seven anxiety items and seven depression items, from which separate anxiety and depression subscale scores are calculated. The mean depression and anxiety scores were 3.6 and 4.7, respectively. Clinically significant depression was recorded in 12.6% of patients, and clinically significant anxiety was recorded in 20.9% of patients, as defined by HADS scores of ≥8.

In univariate analyses, there was no association between anxiety and age or between depression and age. In multivariable analyses, older age (P=.05) was associated with decreased anxiety. Other factors associated with anxiety were a lack of social support (P<.01) and an increased number of comorbidities (P<.01). In multivariable analysis, depression was associated with a lack of social support (P<.01), an increased number of comorbidities (P<.01), and an advanced stage (P<.01).

According to Weiss, “referrals should be made when appropriate (scores of 4 or greater on the Distress Thermometer, 16 on the HADS, and 10 on the GDS) to a social worker who can transfer the patient to an appropriate resource, such as a chaplain, psychiatrist, or psychologist. Research has shown that early evaluation and screening for distress leads to early and timely management of psychological distress, which in turn improves medical management.” For more information, Weiss recommends consulting the National Comprehensive Cancer Network Clinical Practice Guidelines for Distress Screening (www.nccn.org).—Wayne Kuznar

High Prevalence of Bisphosphonate-Associated Esophageal Cancer Reported by FDARequires Further Investigation

A review of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) uncovered 128 cases of bisphosphonate-associated esophageal cancer, and issued a significant safety signal with alendronate. The same research team, however, failed to find an increased risk of esophageal cancer with bisphosphonate use in a large academic medical center. The researchers, led by Beatrice Edwards, MD, associate professor of medicine, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, presented their findings in a poster session at the ASCO meeting, calling for continued investigation into this adverse drug reaction and for increased vigilance when prescribing oral bisphosphonates.

In 2009, the FDA reported on 23 patients who had developed distal esophageal cancer within 2 years of initiating alendronate therapy. In addition, 31 cases of esophageal cancer were reported in Europe and Japan. Esophagitis has been associated with use of oral bisphosphonates; however, a few population studies have failed to find an association between esophageal cancer and bisphosphonate use, said Edwards.

To explore this potential relationship further, the team assessed the FDA AERS for a safety signal for bisphosphonates and esophageal cancer by searching for terms related to esophageal cancer and drug names for bisphosphonates, using a search period of 1996 to 2010.

Of the 128 patients (average age, 72 years) who were identified from AERS as having developed esophageal cancer following bisphosphonate use, 75% (n=96) of these patients had taken alendronate. A significant safety signal was found only for alendronate, with a proportional reporting ratio of 6.4 (P=.001), corrected for time of exposure (alendronate was the first oral bisphosphonate to gain FDA approval).

In an attempt to verify the association, “we wanted to look at a clinical database,” Edwards said. The team therefore conducted a cohort study within the Northwestern University clinical database, which contains 2.4 million individual participants with information about medication use. The total number of bisphosphonate users in the data warehouse was 15,621. Twenty-six cases with esophageal cancer had at least two prescriptions for a bisphosphonate, but in only six of these cases did the bisphosphonate use precede the esophageal cancer. There were 1384 cases of esophageal cancer reported without bisphosphonate use. The odds ratio for bisphosphonate-associated esophageal cancer was 0.6, which was not elevated or significant.

A case-control analysis of these six cases with 183 controls on bisphosphonates who did not develop esophageal cancer revealed that gastroesophageal reflux disease (GERD), hiatal hernia, gastritis, and a history of peptic ulcer disease were reported more commonly in individuals with esophageal cancer.

“Most of us worry about giving bisphosphonates to a patient with Barrett’s esophagus [a condition in which the esophageal lining is damaged by stomach acid] because it’s premalignant, but we’re thinking that we may also want to be more careful with our GERD patients as well, and not be giving them oral bisphosphonates,” Edwards said. “In patients with a history of peptic ulcer disease or active GERD, I’d probably go with an intravenous bisphosphonate or another medication, but I don’t think it’s cause for great alarm. We do need to continue pharmacovigilance.”—Wayne Kuznar

Symposium

Early Functional Decline During Chemotherapy Predicts Worse Survival in Older Patients With Cancer

Loss of autonomy early during cancer treatment is linked to poorer prognosis in older patients. A standard oncologic evaluation of older adults may lead to overtreatment and an excess risk of toxicity, or conversely, undertreatment and loss of efficacy. The geriatric evaluation may be “a good solution to solve these problems,” as it provides an opportunity to better evaluate risks, to better appreciate chances, and to propose tailored treatment strategies, said Pierre-Louis Soubeyran, MD, PhD, Institut Bergonie, Bordeaux, France, during a clinical science symposium at the ASCO meeting.

The appropriate treatment objective in the older cancer patient is optimal tumor control while maintaining quality of life, Soubeyran said. Important events to avoid that may have an impact on treatment strategies are early death, early functional decline, and hospitalization for toxicity. In a multicenter prospective study, researchers set out to examine whether a decrease in autonomy for activities of daily living (ADLs) after a first cycle of chemotherapy influences prognosis in older patients with cancer.

The investigators sought to precisely define and identify predictors of early functional decline. “The Activities of Daily Living Scale is definitely the right tool to use,” said Soubeyran. “The question is, when to use it? We decided to evaluate it early; that is, before the second cycle of chemotherapy.” A small threshold of a reduction of ≥0.5 points on the ADLS (scores range from 6 to 0) was used to define early functional decline.

The study enrolled 364 patients aged >70 years (average age, 77.3 years; 59.2% men) with various kinds of cancer (excluding breast cancer) who were receiving first-line chemotherapy. Of these patients, 299 were evaluable.

Prognostic factors were sought from the pretreatment geriatric assessment data, which included the Cumulative Illness Rating Scale-Geriatric (CIRS-G), Instrumental ADL (IADL), Mini Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), 15-item Geriatric Depression Scale (GDS15), 30-item Quality of Life Questionnaire (QLQ-C30), Eastern Cooperative Oncology Group Performance Scale (ECOG-PS), and Get Up and Go test, as well as from patients’ baseline biological and clinical information (ie, age, sex, tumor extension and localization, performance status, body mass index, weight loss, albumin level, C-reactive protein level, hemoglobin levels, leukocyte and platelet count, and creatinine clearance). Four geriatric assessments were performed: before treatment, before cycles two and four, and at the end of treatment. Patients completely dependent at baseline  (ADL score of 0) were excluded.

Fifty patients (16.7%) experienced early loss of autonomy. At a median follow-up of 5 years, loss of autonomy was associated with a 52% increased risk of death compared with no early functional decline (P=.016). Biological and clinical factors were not associated with loss of autonomy. A low score on the GDS15, the number of dependencies on the IADL, a low score on the MMSE, a slow time on the Get Up and Go, a low score on the ECOG-PS, and a low score on the MNA pretreatment were found to be prognostic of early functional decline in univariate analyses. In the multivariate model, a low score on the GDS15 (odds ratio [OR], 2.4; P=.01) and dependencies on the IADL (OR, 3.0; P=.027) were independently associated with an increased risk of early functional decline.

“Early functional decline has some prognostic value in terms of survival [in elderly patients with cancer], so it’s probably wise to think about using the ADL questionnaire during treatment for these patients,” concluded Soubeyran. “The GDS15 and IADL questionnaires should be evaluated at baseline,” he said, as these scores are predictive of early functional decline.—Wayne Kuznar