An update on the latest developments in clinical and healthcare services research in oncology.
Research Tests Decision Support Technology for Guiding Cancer Screening Choices
The results of a new study indicate that a technology-based intervention could help patients make informed decisions about cancer screening. The study, published in Annals of Family Medicine, tracked the outcomes from the implementation of a decision support module at 12 practices serving over 55,000 patients. The module was embedded in the online portals of 11,458 patients who faced an upcoming decision on breast, colorectal, or prostate cancer screening.
An initial assessment within the module gathered important information, such as patients’ concerns with cancer screening, desired levels of decision support, decision-making style, and optimal method of receiving information on the recommended screening options. Using this feedback, the module created a tailored page that provided the patient’s preferred amount of relevant information using words, numbers, pictures, or stories.
Patients could then indicate whether they had made up their minds on their next steps, and if so, whether they wanted their physician to receive a summary of their decision preferences that included discussion points, patient questions, and the preferred balance of decision making between the patient and the provider. Questionnaires collected feedback on the module from the patient and the clinician after the office visit during which the results were discussed.
Of the 11,458 patients invited to use the module, only 903 of the 2355 who started completed it. Around a quarter of module users clicked on at least 1 educational resource, and patients each accessed an average 3.5 resources. Patients most commonly sought information on options for getting screened (70.8%), what screening test works best (49.8%), and potential complications from screening (45.7%).
Patients who forwarded the decision summary to their physicians were more likely discuss the screening at their next visit, and 80.9% said the conversation helped reduce their fears or worries about screening. A majority of patients agreed that the module was easy to complete and understand, and sizable proportions reported that it had improved their knowledge before the office visit (48.1%) and got them more involved in the screening decision (47.7%). Finally, patients who had completed the module were significantly more likely to undergo screening within 3 months than those who had not started or completed it.
According to the researchers, these findings indicate that technology-enabled decision support initiatives are a feasible way to empower patients in decision making and help improve communication between patients and physicians. They noted that invitation response rates and module completion levels were relatively low, but could potentially increase with better workflow integration. This was also a self-selected sample without a control group, so future trials will need to be randomized and controlled to more fully evaluate the role of decision support technologies in cancer screening and other health choices.
The researchers acknowledged that implementing new technologies within practice workflows will not be an easy task, but if “future research confirms the benefits of this approach—more informed patients, better decisions, and wiser use of encounter time—the return on investment could offset the implementation costs and improve care.”
Krist AH, Woolf SH, Hochheimer C, et al. Harnessing information technology to inform patients facing routine decisions: cancer screening as a test case. Ann Fam Med. 2017;15(3):217-224. doi: 10.1370/afm.2063.
Lowering the Risk of Venous Thromboembolism With Ovarian Cancer Treatment
Surabhi Dangi-Garimella, PhD
Twenty-five percent of patients receiving neoadjuvant chemotherapy treatment for ovarian cancer develop venous thromboembolism (VTE), according to the results of a new study published in the journal Obstetrics & Gynecology.1
Patients with ovarian cancer have historically been associated with developing VTE. Significant risk factors include obesity, older age, advanced disease stage, debulking surgery, and use of anticoagulants. Development of this hematological condition can, in turn, lead to a poor prognosis or a reduced quality of life for patients. Although postoperative efforts have focused on reducing the incidence of thromboembolic events in women with ovarian cancer, the 4-week standard treatment that is currently offered may not be sufficient to reduce the long-term risk.2
With the hypothesis that neoadjuvant chemotherapy increases the incidence of VTE, the authors of the current study conducted a retrospective analysis among 112 patients with ovarian cancer who were being treated with neoadjuvant chemotherapy. Thirteen patients who presented with a symptom of VTE were disregarded prior to analysis. Thirty of the 112 patients at risk (26.8%; 95% CI, 19.3%-35.9%) experienced a VTE. Thirteen patients (11.6%; 95% CI, 6.8%-19.1%) experienced this hematological event during the neoadjuvant chemotherapy treatment, 6 (5.4%; 95% CI, 2.4%-11.5%) developed the condition postoperatively, and 11 (9.9%; 95% CI, 5.5%-17%) developed VTE during adjuvant chemotherapy.
Based on these findings, the authors confirm that neoadjuvant chemotherapy positions patients with ovarian cancer at an extremely high risk of developing VTE. Highlighting the importance of prophylactic treatment in preventing the incidence of VTE, they note that prophylaxis could improve survival in this patient population. This is especially important because of the rapidly growing population of patients with ovarian cancer who are administered neoadjuvant chemotherapy in the United States, they write.
1. Greco PS, Bazzi AA, McLean K, et al. Incidence and timing of thromboembolic events in patients with ovarian cancer undergoing neoadjuvant chemotherapy [published online May 5, 2017]. Obstet Gynecol. 2017. doi: 10.1097/ AOG.0000000000001980.
2. Pant A, Liu D, Schink J, Lurain J. Venous thromboembolism in advanced ovarian cancer patients undergoing frontline adjuvant chemotherapy. Int J Gynecol Cancer. 2014;24(6):997-1002. doi: 10.1097/IGC.0000000000000164.
Pembrolizumab Plus Chemotherapy Approved for Metastatic Nonsquamous NSCLC
Surabhi Dangi-Garimella, PhD
Tumor response rate and progression-free survival (PFS) were the benchmarks that helped pembrolizumab (Keytruda) gain accelerated approval as first-line treatment for metastatic nonsquamous non—small cell lung cancer (NSCLC) in combination with pemetrexed (pem) and carboplatin (carbo), irrespective of PD-L1 expression.
Observations in a subpopulation of patients who were part of the KEYNOTE-021 trial led to the new approval. A cohort of 123 treatment-naïve patients with metastatic nonsquamous NSCLC, with no mutations in EGFR or ALK genes, were treated with pembrolizumab plus pem/carbo or pem/carbo alone. Including pembrolizumab in the treatment regimen improved the objective response rate from 29% (95% CI, 18%-41%) to 55% (95% CI, 42%-68%). Further, a majority of patients (93%) who received pembrolizumab had a duration of response that was at least 6 months (range, 1.4+ to 13+ months) compared with 81% of patients who did not (range, 1.4+ to 15.2+ months). Pembrolizumab also improved the median PFS by about 3.1 months.
With respect to adverse events, pembrolizumab treatment resulted in pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Pembrolizumab can also cause severe or life-threatening infusion-related reactions.
“This approval marks an important milestone in the treatment of lung cancer. Now, pembrolizumab in combination with pemetrexed and carboplatin can be prescribed in the first-line setting for patients with metastatic nonsquamous non—small cell lung cancer, irrespective of PD-L1 expression,” said Corey Langer, MD, director of thoracic oncology and professor of medicine at the Hospital of the University of Pennsylvania.1 Langer emphasized that physicians should consider individual patient characteristics, such as biomarker status, histology, and other clinical factors, to carve out an appropriate treatment plan.
The approval of pembrolizumab as first-line therapy, alone or in combination with chemotherapy agents, has opened up the horizon’s for Merck, the company that developed the molecule. More than 200,000 individuals are diagnosed annually with NSCLC in the United States.2 The drug spend will be an issue, however: the combination of pembrolizumab and chemotherapy will cost more than $250,000 annually.
1. FDA approves Merck’s Keytruda (pembrolizumab) as first-line combination therapy with pemetrexed and carboplatin for patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression [press release]. Kenilworth, NJ; Merck: May 10, 2017. http://www.mrk.newsroom.com/news-release/prescription-medicine- news/fda-approves-mercks-keytruda-pembrolizumab-first-line-combin. Accessed May 11, 2017.
2. What’s new in non-small cell lung cancer research? American Cancer Society website. https://www.cancer.org/cancer/ non-small-cell-lung-cancer/about/new-research.html. Updated May 16, 2016. Accessed May 11, 2017.
USPSTF: Do Not Screen for Thyroid Cancer in Asymptomatic Individuals
Surabhi Dangi-Garimella, PhD
The US Preventive Services Task Force (USPSTF) has provided a D recommendation (discourages the use of service) for thyroid cancer screening in asymptomatic individuals.
Thyroid cancer incidence has increased nearly 3 times over a 40-year period: 15.3 cases per 100,000 persons in 2013 compared with 4.9 cases per 100,000 in 1975. However, mortality rates have not seen much of a spike, increasing by just 0.7 deaths per 100,000 persons each year. It’s also important to note that the 5-year survival for the disease ranges from 99.9% for localized disease to 55.3% for individuals who have metastases.
The USPSTF revisited neck palpation or ultrasound as a screening technique used in asymptomatic individuals to evaluate its impact on health outcomes. The recommendations, however, do not apply to individuals with hoarseness, pain, difficulty swallowing, or other throat symptoms or persons who have lumps, swelling, asymmetry of the neck, or other reasons for a neck examination. They also do not apply to persons at increased risk of thyroid cancer because of a history of exposure to ionizing radiation, particularly persons with a diet low in iodine, an inherited genetic syndrome associated with thyroid cancer, or a first-degree relative with a history of thyroid cancer.
The USPSTF committee found no direct evidence that compared screened versus unscreened populations or immediate surgery versus surveillance or observation that showed an impact on health outcomes, such as mortality, quality of life, or harms. “The USPSTF found inadequate direct evidence on the harms of screening, but determined that the magnitude of the overall harms of screening and treatment can be bounded as at least moderate, given adequate evidence of harms of treatment and indirect evidence that overdiagnosis and overtreatment are likely to be substantial with population-based screening,” the authors noted.
The research, according to the report published in JAMA, points to the need for observational studies of early treatment versus surveillance or observation of patients with small, well-differentiated thyroid cancer to identify patients at highest risk for clinical deterioration. The experts also noted the absence of risk prediction tools or biomarkers to understand the prognosis of differentiated thyroid cancer.
While there is no direct evidence proving that screening for thyroid cancer can result in overdiagnosis, the fact that increased incidence has not resulted in increased mortality is telling, according to the report. “Overdiagnosis occurs because screening for thyroid cancer often identifies small or slow-growing tumors that might never affect a person during their lifetime,” committee member Seth Landefeld, MD, said in a statement for USPSTF. “People who are treated for these small tumors are exposed to serious risks from surgery or radiation, but do not receive any real benefit.”
Bibbons-Domingo K, Grossman DC, Curry SJ; US Preventive Services Task Force. Screening for thyroid cancer: US Preventive Services Task Force recommendation statement. JAMA. 2017;317(18):1882-1887. doi: 10.1001/jama.2017.4011.
Screening Rate Disparities for Some Cancers May Have Decreased After ACA, Study Finds
According to a new study, although socioeconomic disparities in mammography rates among Medicare beneficiaries decreased after the implementation of the Affordable Care Act (ACA), the same pattern was not observed for colonoscopies. The researchers hypothesize that the free preventive services required under the ACA may have removed cost as a barrier, but other obstacles to cancer screening persist.
The study, published in Cancer, looked at 2 samples of Medicare beneficiaries aged 70 or older and determined whether they had received the recommended cancer screening based on the date of their most recent preventive mammography or colonoscopy. They also collected information on patients’ cancer risk factors and county-level income and education data. The mammography analysis included a sample of over 862,000 women, and the colonoscopy sample included over 326,000 men and women.
The researchers explained that the ACA’s provision eliminating out-of-pocket costs to patients for preventive services was intended to expand access to screening and reduce disparities, but few studies had compared screening rate changes after the ACA. Thus, their study conducted analyses to compare screening rates and their relation to income and education factors in the 2-year period before the ACA was implemented (2009 to 2010) and the 2-year period after implementation (2011 to 2012).
For the mammography group, the researchers found an association between lower socioeconomic status and decreased mammography rates, both before and after the ACA, but the disparities decreased significantly after the law’s implementation. The odds ratio for the women in the lowest-income quartile receiving a mammogram compared with those in the highest quartile increased from 0.87 to 0.94 after the ACA, while the corresponding odds ratios for education quartiles increased from 0.76 to 0.86. From the pre-ACA period to the post-ACA period, the researchers found that mammography rates increased within each quartile of income and education.
In the colonoscopy analysis, however, the researchers observed a slight decrease in colonoscopy rates after the ACA was implemented, finding there were no significant changes in the associations between socioeconomic indicators and screening rates over the study period. “The interaction tests indicate that the effects of income, education, and quartile did not differ significantly between the 2 time periods,” the authors wrote, acknowledging that they could not establish a causal relationship between the ACA and screening rates.
They wrote that the mammography findings indicated that the financial cost of preventive services may have been a potential obstacle to cancer screening, but it is far from the only factor. “The findings support the removal of out-ofpocket expenditures as a barrier to the receipt of recommended preventive services, but emphasize that for colonoscopy, other factors such as a fear of sedation, perceived discomfort, and a need for bowel preparation should be considered,” they concluded.
The researchers also suggested that further studies be undertaken to assess the effects of the ACA on screening rates among other populations, such as people who gained insurance coverage under the law.
Cooper GS, Kou TD, Dor A, Koroukian SM, Schluchter MD. Cancer preventive services, socioeconomic status, and the Affordable Care Act. Cancer. 2017;123(9):1585-1589. doi: 10.1002/cncr.30476.
Avalere and FasterCures Release Patient-Perspective Value Framework 1.0
Surabhi Dangi-Garimella, PhD
A yearlong collaboration between a health consultancy and a think tank has resulted in the first draft of a framework that considers the value of healthcare services from the patient’s perspective—the Patient Perspective Value Framework (PPVF).
Avalere Health and FasterCures, a center of The Milken Institute, initiated a collaboration in June 2016 to develop the PPVF. The objective was to incorporate the framework, or parts of it, into existing value framework platforms, including the American Society of Clinical Oncology (ASCO)’s Value Framework,1 the Institute for Clinical and Economic Research (ICER)’s Value Assessment Framework,2 and the National Comprehensive Cancer Network (NCCN)’s Evidence Blocks.3
The 2 organizations convened multiple stakeholders to steer the development of PPVF, including patient groups (Cancer Support Community, Leukemia & Lymphoma Society, Michael J Fox Foundation, and National Multiple Sclerosis Society), healthcare think tanks (FasterCures, National Health Council, Partnership to Improve Patient Care, and Patient-Centered Outcomes Research Institute), payers (Aetna and CVS Health), pharmaceutical developers and their representatives (Amgen, Astellas Pharma, Biogen, Edwards Lifesciences, Gilead Sciences, GlaxoSmithKline, Johnson & Johnson, Pharmaceutical Research and Manufacturers of America, and Sanofi), and others (American Heart Association and Better Medicare Alliance).
“As the US healthcare system transitions to value-based payment, it is imperative that we get the value definition right and measure what truly matters to the patient,” Josh Seidman, senior vice president in Avalere’s Center for Payment and Delivery Innovation, said in a statement.4 He believes that PPVF can assist healthcare organizations integrate what matters to patients in their payment models.
There are 5 components that reside within this framework:
The developers of the PPVF envision using this framework for shared decision-making, incorporating it within existing value frameworks, supporting public health programs, and to inform patient-centered drug development.
Future plans include collaborating with other framework developers, and to that effect, representatives from ASCO, ICER, NCCN, and Memorial Sloan Kettering’s DrugAbacus participated in a meeting with PPVF’s steering committee to discuss potential opportunities for collaboration.
The next phase of the initiative is expected to kick off in June 2017.
1. Dangi-Garimella S. ASCO releases an updated value framework. The American Journal of Managed Care® website. http://www.ajmc.com/newsroom/asco-releases-an-updated-value-framework. Published May 31, 2016. Accessed May 18, 2017.
2. Dangi-Garimella S. ICER’s updated value framework open for public comment. The American Journal of Managed Care® website. http://www.ajmc.com/newsroom/icers-updated-value-framework-open-for-public-comment. Published May 31, 2016. Accessed May 18, 2017.
3. Dangi-Garimella S. Weighing value and patient preference in cancer care: NCCN Evidence Blocks. The American Journal of Managed Care® website. http://www.ajmc.com/conferences/nccn-2016/weighing-value-and-patient-preference- in-cancer-care-nccn-evidence-blocks-. Published May 31, 2016. Accessed May 18, 2017.
4. Avalere and FasterCures Release Patient-Perspective Value Framework to incorporate patient preferences into healthcare treatment decisions [press release]. Washington, DC: Avalere; May 11, 2017. http://avalere.com/expertise/ life-sciences/insights/avalere-health-and-fastercures-release-version-1.0-of-the-patient-perspecti. Accessed May 18, 2017.