Medical World News®, October 2017

Mammography Device Approved by FDA Gives Patients Control Over Pressure Levels

Christina Mattina

The FDA has approved the first 2D digital mammography system that lets patients adjust the level of compression applied to their breast during the imaging procedure.

Mammograms are a key tool in detecting breast cancer, but some women report discomfort with the procedure, which requires the breast to be compressed in order to capture a 2D x-ray image. The new device could potentially expand uptake of mammograms by empowering patients and making the experience more comfortable.

According to the FDA announcement, the Senographe Pristina with Self-Compression, manufactured by GE Healthcare, was approved through the premarket 510(k) pathway.¹ GE had to demonstrate that the new device is clinically equivalent to the Senographe Pristina, an approved digital mammography device that allows the technician operating the device full control over compression.

The self-compression device differs from the original machine by including a wireless remote control held by the patient that can adjust the compression force. After the technologist positions the patient’s breast, the patient is asked to use the remote control to gradually increase the level of compression to a point she finds tolerable. The technician then checks whether the compression is sufficient to achieve a clear image and can adjust it if necessary.

Trials conducted as part of the premarket approval process confirmed that allowing patients to control compression with the remote control did not diminish image quality compared with the device now in use. The average time of the mammogram did not increase either. The finding that the new device was at least as safe and effective as the approved device contributed to the FDA’s decision to grant premarket clearance to GE.

“Regular mammograms are an important tool in detecting breast cancer. However, some patients may experience anxiety or stress about the discomfort from the compression during the mammogram,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, in the announcement. “This device allows patients some control over the amount of compression for their exam.”

This sense of control, along with reduced pain and discomfort, could have significant implications for changing women’s perceptions of mammography and their willingness to undergo screening. A 2013 review published in The Breast showed that between 25% and 46% of women who did not return for subsequent mammograms cited pain during the initial mammogram as the reason.²

References:

1. FDA clears mammography device with option for patient-assisted compression [press release]. Silver Spring, MD: FDA; September 1, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574562.htm. Accessed September 5, 2017.

2 Whelehan P, Evans A, Wells M, Macgillivray S. The effect of mammography pain on repeat participation in breast cancer screening: a systematic review. Breast. 2013;22(4):389-394. doi: 10.1016/j.breast.2013.03.003.

FDA Emphasizes Risks of Pembrolizumab in Multiple Myeloma After Reviewing Halted Trials

Christina Mattina

Less than two months afterit ordered a stop to 3 trials of pembrolizumab (Keytruda) in multiple myeloma due to safety concerns, the FDA has released a more detailed analysis of what went wrong in the trials.

Merck, which developed pembrolizumab, announced in July that the FDA had placed 2 phase 3 studies on full hold and a phase 1 study on partial hold, citing a pattern of patient deaths.¹ The FDA’s safety alert, issued recently to healthcare providers, oncology researchers, and the public, analyzes data from the 2 phase 3 trials that were halted completely.²

KEYNOTE-183 had been studying pembrolizumab in combination with pomalidomide and low-dose dexamethasone in patients with relapsed/ refractory multiple myeloma. KEYNOTE-185 was assessing pembrolizumab in combination with lenalidomide and low-dose dexamethasone in those with newly diagnosed and treatment-naïve multiple myeloma.

KEYNOTE-183 documented 29 deaths in the investigational arm receiving pembrolizumab and 21 deaths in the control arm. The FDA determined that the relative risk of death was 61% higher for participants in the pembrolizum- ab arm. This increased hazard was not accompanied by improved outcomes, as the objective response rate was 34% in the investigational arm and 40% in the control group. Patients receiving pembrolizumab were also more likely to experience a higher rate of grade 3 to 5 toxicities than their counterparts in the control arm (83% vs 65%, respectively), as well as serious adverse events (63% vs 46%). The most common causes of death unrelated to cancer progression in the pembrolizumab arm included several heart-related conditions, neutropenic sepsis, and multiple organ dysfunction.

The KEYNOTE-185 trial appeared to pose even more risk to participants. There were 19 deaths in the investigational arm and 9 in the control group, indicating a risk of death that was over 2-fold for the patients receiving pembrolizumab. Higher incidences of grade 3 to 5 toxicities (72% vs 50%) and serious adverse events (54% vs 39%) were observed in the pembrolizumab arm than in the control arm.

Noncancer causes of death in the investigational arm of KEYNOTE-185 included the cardiac events seen in KEYNOTE-183, intestinal ischemia, suicide, and sudden death. The objective response rate in the pembrolizumab arm was 64%, compared with 62% seen in the control arm.

Both the data analysis and a press statement³ from the FDA emphasized that these safety risks only apply to multiple myeloma, which is not an approved indication of pembrolizumab, and that patients taking the drug for approved indications—which include melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, and others—should continue to do so.

“Today’s alert underscores the importance of why new therapies are thoroughly studied to ensure the benefits of taking them outweigh the risks to patients, and we will continue to aggressively monitor clinical trials to ensure patients are protected when safety concerns arise,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, in the announcement.

References:

1. Mattina C. FDA halts some pembrolizumab trials for multiple myeloma, citing patient deaths. The American Journal of Managed Care^® website. ajmc.com/newsroom/fda-halts-some-pembrolizumab-trials-for-multiple-myeloma-cit-ing-patient-deaths. Published July 7, 2017. Accessed September 1, 2017.

2. FDA alerts healthcare professionals and oncology clinical investigators about two clinical trials on hold evaluating Keytruda (pembrolizumab) in patients with multiple myeloma [press release]. Silver Spring, MD: FDA; August 31, 2017. www.fda.gov/Drugs/DrugSafety/ucm574305.htm. Accessed September 1, 2017.

3. Statement from Center for Drug Evaluation and Research Director Janet Woodcock regarding safety concerns related to investigational use of Keytruda in multiple myeloma [press release]. Silver Spring, MD: FDA; August 31, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574341.htm. Accessed September 1, 2017.

Race, Socioeconomic Status Linked to Rehospitalizations Among Patients With Advanced Cancer

staff

AJMC

A new study in the Journal of Clinical Oncology identifies an increased role for physicians in boosting human papillomavirus (HPV) vaccination rates among childhood cancer survivors to reduce their risk of a second cancer.¹

The study surveyed 982 childhood cancer survivors (the majority of whom were leukemia/lymphoma survivors), aged 9 to 26 years, who had completed treatment between 1 and 5 years prior to the survey. The survey touched on:

• Whether they had received an HPV vaccine
• Whether their provider had recommended the vaccine
• Their attitude toward vaccination

The results drawn on the HPV vaccination rates were compared with the vaccine initiation rates in the general population. More than a 1.5-fold difference was noted between the 2 populations: a 24% vaccination rate among the childhood cancer survivors compared with 40% in the general-population peers. Males, overall, were more likely to get vaccinated.

The biggest difference, the study noted, was among teens 13 to 17 years of age: 22% for cancer survivors compared with 42% for their general population peers. However, the numbers were on par in the older population (18 to 26 years old): 25% for survivors and 24% for their general population peers.

With nearly 7 million adolescents and young children infected with HPV annually, the virus has a significant bearing on the incidence of cervical cancers and many oral, anal, vaginal, vulvar, and penile cancers. Childhood cancer survivors are particularly susceptible to HPV infection due to their already weakened immune system post cancer treatment. This has led organizations, like the American Society of Clinical Oncology, to recommend that girls and boys should be vaccinated against HPV to reduce the incidence of cancer.

The current study identified lack of physician recommendation as being the biggest barrier to vaccination: 72% did not get a recommendation and only 5% of those surveyed ended up getting vaccinated. The most important finding was, of the 28% who received a recommendation from their physicians, more than half got vaccinated.

“This study shows that an effective, affordable, and widely available tool for cancer prevention is being underutilized by survivors of childhood cancer,” said study author James Klosky, PhD, ABPP, an associate member at St. Jude Children’s Research Hospital in Memphis, Tennessee, in a statement. “As clinicians, we need to initiate more conversations about HPV vaccination, especially with childhood cancer survivors, because they stand to benefit even more than their peers.”

Next, Klosky said, researchers must develop interventions that ensure clear communication between a patient’s survivorship and primary healthcare teams, so that appropriate measures are in place for care continuity.

References:

Klosky JL, Hudson MM, Chen Y, et al. Human papillomavirus vaccination rates in young cancer survivors [published online August 24, 2017]. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.74.1843.

Financial Concerns Influence Care-Seeking Behavior of Childhood Cancer Survivors

Surabhi Dangi-Garimella, PhD

High out-of-pocket (OOP) medical costs in survivors of childhood cancer can influence their treatment choices and care-related behavior and ultimately affect their health outcomes. This was the conclusion of a study that evaluated the prevalence of financial burden in this patient population.¹

High treatment costs, particularly for diseases that require long-term follow-up or long-term care, can be a financial strain for patients. Studies have shown that financial burden in adult patients with cancer can prove a negative influence on outcomes, including their quality of life, symptom burden, and survival. In the current study, the authors queried whether survivors of childhood cancer experience a financial burden and is this associated with high OOP costs and alterations in the patients’ lifestyle or care-seeking patterns.

The authors studied an age-stratified sample of childhood cancer survivors (n = 580) and used their siblings as a comparison group (n = 173). The survivor pool, which included patients who had enrolled in the Childhood Cancer Survivor Study—a longitudinal follow-up that compares health outcomes of survivors of childhood cancer with those of siblings—shared their household income, OOP medical costs, and issues related to financial burden. The 580 participants who shared their financial information were more likely to be married and to have higher education and higher household incomes compared with the original 1101 survivors that the authors had selected for this study.

Compared with their siblings, survey participants were:

• Male (46.7% vs 37.1%; P = .025)
• Unmarried (35.4% vs 24.6%; P = .008)
• Had severe to life-threatening chronic medical conditions (39.7% vs 17.1%; P <.001)
• Have Medicare (5.8% vs 1.1%; P = .011) or Medicaid/state insurance (11.5% vs 4.6%; P = .008)

Survivors of childhood cancer were more likely to have OOP medical costs that were 10% or higher of their annual income compared with 2.9% for the sibling (P < .001). The primary reason for higher OOP spending was hospitalization in the past year (OR, 2.3; 95% CI, 1.1-4.9) and annual household income less than $50,000 (OR, 5.5; 95% CI, 2.4-12.8). Additionally, higher OOP spending had a significant association with:

• Problems paying medical bills (OR, 8.9; 95% CI, 4.4-18.0)
• Deferring care for a medical problem (OR, 3.0; 95% CI, 1.6-5.9)
• Skipping a test, treatment, or follow-up (OR, 2.1; 95% CI, 1.1-4.0)
• Thoughts of filing for bankruptcy (OR, 6.6; 95% CI, 3.0-14.3)

The survey results showed a strong association between survivors with a high OOP medical spend and financial burden, the authors note. More importantly, although survivors were an average 30 years from their cancer diagnosis, many continued to struggle with OOP medical costs and their associated financial burden.

The authors believe that their study, which identified characteristics of the most financially vulnerable patients, can be used to proactively target specific patients at high risk of financial burden.

References:

Nipp RD, Kirchhoff AC, Fair, et al. Financial burden in survivors of childhood cancer: a report from the childhood cancer survivor study [published online August 17, 2017]. J Clin Oncol. 2017:JCO2016717066. doi: 10.1200/ JCO.2016.71.7066.

What Is the Ideal Age for Screening Mammography?

Surabhi Dangi-Garimella, PhD

The conflict over the recommended age for a screening mammogram continues with a new study whose authors conclude that an annual screening starting at age 40 has the greatest impact on reducing mortality.¹

The study used mean values from 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models to compare 3 recommendations from major healthcare organizations:

• Annual screening at ages 40 to 84 years
• Screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years
• Biennial screening at ages 50 to 74 years

Per their analysis, the highest reduction in mortality was observed in the cohort that started annual screening at age 40 and continued until age 84 years (mean reduction, 39.6%). The second highest mortality reduction was observed in the hybrid group (mean reduction 30.8%)—this group initiated their annual screening at age 45 and continued until age 54, followed by biennial screening from 55 to 79. The group that followed the biennial screening recommendation between 50 to 74 years had the lowest reduction in mortality (23.2%).

The analysis showed that for a single-year cohort of women aged 40 years, an annual screening mammogram initiated at age 40 would prevent 29,369 deaths. This compared with 22,829 lives saved due to the hybrid screening and 15,599 lives from the biennial screening (based on 2016 CISNET estimates).

“Our findings are important and novel, because this is the rst time the 3 most widely discussed recommendations for screening mammography have been compared head-to-head,” senior author Elizabeth Kagan Arleo, MD, of Weill Cornell Medicine, said in a statement. “Our research would be put to good use if, because of our findings, women chose to start annual screening mammography starting at age 40. Over the long term, this would be significant because fewer women would die from breast cancer.”² Arleo would like women and their physicians to use the findings of this analysis to guide screening choices with respect to initiation and frequency of screening.

In an accompanying editorial, Otis Brawley, MD, FACP, chief medical officer of the American Cancer Society, highlighted the importance of an individual’s value judgement.³ “Our goal should be to provide truthful, balanced information so that women can make informed choices about when to start screening for breast cancer. A woman who is making a decision about screening is more interested in her personal chances of bene t and risk of harm and is less interested in the benefits to the population,” he wrote.

His editorial also pointed out the limitations of a mammogram and emphasized the importance of a better test for women that would avoid false positives and be more sensitive.

References:

1. Arleo EK, Hendrick R, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models [published online August 21, 2017]. Cancer. 2017. doi: 10.1002/cncr.30842.

2. Arleo EK, Hendrick R. Comparison of screening recommendations indicates annual mammography starting at 40 prevents most cancer deaths. Wiley website. newsroom.wiley.com/press-release/cancer/comparison-screening-rec- ommendations-indicates-annual-mammography-starting-age-. Published August 21, 2017. Accessed August 23, 2017.

3. Brawley OW. On assessing the effect of breast cancer screening schemes [published online August 21, 2017]. Cancer. doi: 10.1002/cncr.30840.

5 Takeways for Payers, Providers From the NCCN Meeting on Quality Metrics

Surabhi Dangi-Garimella, PhD

The National Comprehensive Cancer Network (NCCN) chose a very appropriate topic for this year’s policy meeting: Redefining Quality Measurement in Oncology. While “measure, measure, measure” has been the mantra in healthcare, defining what, when, and how to measure remains a challenge. However, with value-based care and alternative payment models experimenting with identifying appropriate quality measures, defining the right metric has become more urgent than ever.

Following are a few takeaways from the NCCN summit, which was held September 25, 2017, in Washington, DC.

1. A voice for the patient. Ronald Walters, MD, MBA, MHA, MS, associate vice president of medical operations and informatics, The University of Texas MD Anderson Cancer Center, said that the value-based care movement has finally moved away from being provider-centric to being patient-centric. While provider-centric measures of care are important, patient-centric measures of value, including patient experience (eg, satisfaction), engagement, and outcomes, are vital, he said.

2. Quality for whom? During her presentation, Mary Lou Smith, JD, MBA, cofounder, Research Advocacy Network, asked who was at the receiving end of the quality measures: the care provider, the patients, or the healthcare system? “Patients know when they have answers to their questions, but patients don’t know what questions to ask,” Smith said. This then pushes the onus on the stakeholders responsible for patient care to identify the right measures that can ensure good

health outcomes.

3. Challenges with identifying the right measures. On a panel that saw representation of patient advocates, oncologists, health policy researchers, health plans, and the pharmaceutical industry, the discussion revolved around ways to gather the right evidence for quality measurement to improve outcomes. “We don’t just have to measure everything, but we do need to understand the accuracy of what we are measuring. We definitely need a quality measure to understand patients’ comprehension of their treatment and disease,” said John Fox, MD, MS, medical director, Priority Health. Panelists agreed, however, that accountability for quality care rests on all stakeholders.

4. Best practices in quality measurement. Kerin Adelson, MD, medical oncologist, Yale Cancer Center/Smilow Cancer Hospital, presented her research on how their health system grappled with teasing out the right structured and unstructured data in collaboration with Flatiron Health. She pointed out that while provider attribution is hard, particularly when mapping out care delivered to a patient in the oncology space, they have been using information extracted via Flatiron’s technology platform.

“Provider level view will lead to change,” Adelson said, adding that their research team plans to develop national benchmarks for quality using Flatiron’s database.

5. Looking to the future. Adelson then sat on a panel with Basit Chaudhry, MD, PhD, Tuple Health; Joanne Buzaglo, PhD, Cancer Support Community; Virginia Calega, MD, MBA, Independence Blue Cross; Peter Ellis, MD, University of Pittsburgh Cancer Institute; and Marcus Neubauer, MD, McKesson Specialty Health. The experts discussed how providers in the community and health systems are working in tandem with health plans and technology companies to navigate the maze of value-based care.

Panelists agreed that healthcare providers cannot shy away from changes within our care delivery system and that they need to keep up with the dynamic nature of payment reform.