News From JCO and JOP

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STAYING UP-TO-DATE in the fast-paced world of oncology literature is a daunting task at best. To assist with that task, The ASCO Post has assembled an assortment of studies recently published in the Journal of Clinical Oncology (JCO) and the Journal of Oncology Practice (JOP). Future installments will provide readers with snapshots of literature published in these publications as well as ASCO’s newest online journals, the Journal of Global Oncology, JCO Precision Oncology, and JCO Clinical Cancer Informatics

Cabozantinib Salvage Therapy in Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer 

Manisha H. Shah, MD

Manisha H. Shah, MD

A PHASE II STUDY has shown that cabozantinib (Cometriq) produces responses in patients with tyrosine kinase inhibitor–refractory differentiated thyroid cancer. The findings were reported by Cabanillas et al in the Journal of Clinical Oncology. MET plays a role in vascular endothelial growth factor receptor (VEGFR) inhibitor resistance. Cabozantinib is a multi–tyrosine kinase inhibitor that blocks MET and VEGFR and is currently approved for use in medullary thyroid cancer. 

Study Details 

The study included 25 patients with radioiodine-refractory differentiated thyroid cancer who had progression on VEGFR inhibitor therapy, including 21 who had received 1 inhibitor (sorafenib [Nexavar], pazopanib [Votrient], or cediranib) and 4 who had received 2 inhibitors. Patients had a median age of 64 years. Cabozantinib was started at 60 mg/d and could be increased to 80 mg/d in the absence of response. 

Response Rates 

Among the 25 patients, 7 were treated at 60 mg/d, 4 had escalation to 80 mg/d, and 14 had dose reductions to 40 mg/d (n = 6) or 20 mg/d. Median duration of follow-up was 22.8 months. Response was observed in 10 patients (40%, all partial responses) and was observed at all dose levels; stable disease was observed in 13 patients (52%). Responses were observed only among patients who had received only one prior VEGFR inhibitor. 

Median progression-free survival was 12.7 months, with 12- and 24-month progression-free survival rates of 55% and 25%, respectively. Median overall survival was 34.7 months, with 12- and 24-month survival rates of 80% and 66%, respectively. 

The most common treatment-related adverse events of any grade (> 40% of patients) were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. The most common treatment-related grade 3 adverse events were hypophosphatemia (16%), fatigue (12%), weight loss (12%), lipase/amylase elevation (12%), and neutropenia (12%). One death (death not otherwise specified) was considered related to study treatment. 

The investigators concluded: “Cabozantinib demonstrated clinically significant, durable objective response activity in patients with [radioactive iodine]-refractory [differentiated thyroid cancer] who experienced disease progression while taking prior VEGFR-targeted therapy.” ■

The study was supported in part by a grant from the International Thyroid Oncology Group. 

Manisha H. Shah, MD, of The Ohio State University, is the corresponding author of the Journal of Clinical Oncology article. 

Cabanillas ME, et al: J Clin Oncol. August 17, 2017 (early release online). 

Alzheimer’s Disease Risk in Medicare Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer 

Clement Joseph McDonald, MD

Clement Joseph McDonald, MD

AS REPORTED by Baik et al in the Journal of Clinical Oncology, Medicare patients who received androgen-deprivation therapy for prostate cancer do not appear to be at increased risk for Alzheimer’s disease and may have an extremely small increased risk for dementia. 

The study involved 1,238,879 Medicare beneficiaries aged ≥ 67 years from the Medicare claims database who developed prostate cancer between 2001 and 2014. Of them, 440,129 (35%) received androgen-deprivation therapy. Separate analyses were performed for risks for diagnoses of Alzheimer’s disease and dementia according to androgen-deprivation therapy use. 

Risk of Alzheimer’s Disease and Dementia 

Among all patients, 8.9% developed Alzheimer’s disease, 18.8% developed dementia, and 26% to 33% died without developing either disease during approximately 7 million years of follow-up. In the Alzheimer’s disease analysis, for androgen-deprivation therapy recipients vs nonrecipients, crude rates per 1,000 patient-years were 17.0 vs 15.5 for Alzheimer’s disease and 73.0 vs 51.6 for all-cause mortality. 

In an unadjusted analysis of dementia, the crude rates for dementia were 38.5 vs 32.9 per 1,000 patient-years. In competing risks analyses adjusting for other cancer treatments and covariates, androgen-deprivation therapy was not associated with an increased risk of Alzheimer’s disease (subdistribution hazard ratio [SHR] = 0.98, 95% confidence interval [CI] = 0.97–0.99) and was associated with a 1% increased risk of dementia (SHR = 1.01, 95% CI =1.01–1.02). Patients receiving androgen-deprivation therapy were more likely vs nonrecipients to die before progression to Alzheimer’s disease (SHR = 1.24, 95% CI = 1.23–1.24) or dementia (SHR = 1.26, 95% CI = 1.25–1.26). 

The investigators concluded: “These data suggest that [androgen-deprivation therapy] treatment has no hazard for [Alzheimer’s disease] and no meaningful hazard for dementia among men age 67 years or older who are enrolled in Medicare.” ■ 

The study was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health. 

Clement Joseph McDonald, MD, of the National Library of Medicine, National Institutes of Health, is the corresponding author of the Journal of Clinical Oncology article. 

Baik SH, et al: J Clin Oncol. August 25 (early release online). 

Association of Supplemental Vitamin B Use and Lung Cancer in VITAL Cohort 

IN A STUDY reported in the Journal of Clinical Oncology, Brasky et al found that the use of individual source supplemental vitamins B6 and B12 was associated with an increased risk of lung cancer among men in the Vitamins and Lifestyle (VITAL) cohort. Several B vitamins, including B6, B9 (folate), and B12, interact with homocysteine and methionine in the one-carbon metabolism pathway, which plays a role in DNA integrity maintenance and regulation of gene expression; this interaction may cause disruption of pathway processes and promote carcinogenesis.

Vitamin B supplements are not chemopreventive for lung cancer and may be harmful.
— Chi-Ling Chen, PhD, and colleagues

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The study involved 77,118 participants in the VITAL cohort aged 50 to 76 years of age who were recruited between October 2000 and December 2002; the cohort was designed specifically to examine potential associations between supplement use and cancer risk. A total of 808 incident primary invasive lung cancers were identified. The exposure of primary interest was 10-year average daily dose from individual and multivitamin supplements. 

Associations With Lung Cancer 

Use of supplemental vitamins B6, folate, and B12 was not associated with an increased lung cancer risk among women. On multivariate analysis, use of vitamin B6 (hazard ratio [HR] = 1.84, 95% confidence interval [CI] = 1.01–3.36) and B12 (HR = 2.42, 95% CI = 1.49–3.95) from individual supplement sources but not from multivitamins was associated with an increased risk of disease in men. Based on 10-year average daily dose, an increased risk was restricted to men in the highest categories of supplemental intake of vitamin B6 (> 20 mg/d; HR = 1.82, 95% CI = 1.25–2.65) and B12 (> 55 μg/d; HR = 1.98, 95% CI = 1.32–2.97) vs nonusers. The risk was higher among men who were cigarette smokers at baseline. The association of supplemental B6 and B12 intake and risk was present for all histologic subtypes except adenocarcinoma, the subtype with the least-strong association with smoking. 

The investigators concluded: “This sex- and source-specific association provides further evidence that vitamin B supplements are not chemopreventive for lung cancer and may be harmful.” ■

The study was supported by National Institutes of Health grants. 

Chi-Ling Chen, PhD, of the College of Medicine, National Taiwan University, is the corresponding author of the Journal of Clinical Oncology article. 

Brasky TM, et al: J Clin Oncol. August 22, 2017 (early release online). 

Assessment of Embedding Palliative Care Nurse Practitioners in Oncology Clinics 

IN A STUDY reported by Walling et al in the Journal of Oncology Practice, the embedding of a palliative care nurse practitioner in an oncology clinic resulted in improved hospice referral, advance care planning documentation, and referral for psychosocial support. 

Anne M. Walling, MD, PhD

Anne M. Walling, MD, PhD

The study compared health-care outcomes over 1 year between 2 oncology clinics in the University of California Los Angeles (UCLA) health system with an embedded palliative care nurse practitioner and 35 clinics without the nurse practitioner intervention. During the intervention period (March 2014 to March 2015), 2,370 patients with advanced cancer were treated in the control clinics, and 224 were treated in the 2 clinics with the embedded nurse practitioner. 

Improvements in Care 

During the intervention period, patients in the intervention group were more likely to have hospice referral before death (53% vs 23%, P = .02), advance care planning documentation (30% vs 17%, P < .01), and referral for psychosocial support (46% vs 16%, P < .01). Overall, among the patients treated by the nurse practitioner, 96% had documented advance care planning, 66% received psychosocial support, and 85% of those dying did so in hospice. There were no significant differences between the groups in the hospital or intensive care unit stays in the 30 days before death. 

Efficiency evaluation indicated that approximately half the time spent by the palliative care nurse practitioner was devoted to tasks that could have been completed by such other personnel as nurses, social workers, or administrative staff. 

The investigators concluded: “An embedded palliative care [nurse practitioner] model using scalable implementation strategies can improve advance care planning and hospice use among patients with advanced cancer.” 

The study was supported by the California Health Care Foundation Payer-Provider Partnerships to Expand Community-Based Palliative Care. ■

Anne M. Walling, MD, PhD, of UCLA, is the corresponding author of the Journal of Oncology Practice article. 

Walling AM, et al: J Oncol Pract. 13:e792-e799, 2017. 

Survival After In-Hospital Cardiac Arrest in Patients With Advanced Cancer 

IN A STUDY reported in the Journal of Oncology Practice, Bruckel et al found that among patients with in-hospital cardiac arrest, those with advanced cancer had lower survival rates and were more frequently designated Do Not Attempt Resuscitation (DNAR) within 48 hours after return of spontaneous circulation. 

Jeffrey T. Bruckel, MD, MPH

Jeffrey T. Bruckel, MD, MPH

The study included identification of 47,157 adults with in-hospital cardiac arrest with and without advanced cancer (defined as metastatic or hematologic malignancy) from the Get With The Guidelines–Resuscitation registry at 369 hospitals from April 2006 through June 2010. The study population excluded patients who were in perioperative areas or certain procedural areas (eg, cardiac catheterization laboratory or interventional radiology), emergency departments, or rehabilitation areas; those with implantable cardioverter-defibrillators or an arrest duration of < 2 minutes without return of spontaneous circulation; and those who were missing pertinent demographic or event data. 

Overall, 6,585 patients with in-hospital cardiac arrest (14%) had advanced cancer. Patients with advanced cancer were younger, had fewer interventions in place at the time of cardiac arrest, were less likely to be in the intensive care unit at the time of arrest, more likely to have pulseless electrical activity as the initial cardiac arrest rhythm, and more frequently treated at teaching hospitals. 

Differences in Survival 

Patients with advanced cancer had lower multivariate-adjusted rates of return of spontaneous circulation (52.3% vs 56.6%, relative risk [RR] = 0.93, P < .001) and survival to discharge (7.4% vs 13.4%, RR = 0.55, P < .001) compared with patients without advanced cancer. Among patients who died during resuscitation, those with advanced cancer had a better performance on most resuscitation quality measures (eg, duration of resuscitation, chest compressions within 2 minutes, defibrillation within 2 minutes for ventricular fibrillation [VF] or ventricular tachycardia [VT] patients, and adrenaline/epinephrine within 5 minutes for non-VF/non-VT patients on adjusted analysis). 

Among patients with return of spontaneous circulation, those with advanced cancer were made DNAR more frequently within 48 hours (37.3% vs 27.1%, RR = 1.38, P < .001). In an analysis of survival to discharge among survivors of initial arrest, adjustment for DNAR status reduced the difference between the advanced cancer group vs the no–advanced cancer group, with the difference remaining significant (from RR = 0.61, P < .001 to RR = 0.74, P <.001, after adjustment for DNAR status). 

The investigators concluded: “Patients with advanced cancer can expect lower survival rates after [in-hospital cardiac arrest] compared with those without advanced cancer, and they are more frequently made DNAR within 48 hours of [return of spontaneous circulation]. These findings have important implications for discussions of resuscitation care wishes with patients and can better inform end-of-life discussions.” 

The study was supported by grants from the National Heart Lung and Blood Institute and Veterans Administration Health Services Research and Development. 

Jeffrey T. Bruckel, MD, MPH, of the University of Rochester Medical Center, is the corresponding author of the Journal of Oncology Practice article. ■

Bruckel JT, et al: J Oncol Pract. August 1, 2017 (early release online). 

News From JCO and JOP is written for The ASCO Post by Matthew Stenger. To view the full articles referenced herein, visit