Clinical Insights: August 2016

Tuesday, August 23, 2016

Release Date: August 23, 2016
Expiration Date: August 23, 2017


This activity is provided free of charge.

STATEMENT OF NEED

This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.
TARGET AUDIENCE

Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may articipate in this CE activity.
 
EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:
  • Describe new preventive options and treatments for patients with cancer
  • Identify options for individualizing the treatment for patients with  cancer
  • Assess new evidence to facilitate survivorship and supportive care for patientswith cancer
ACCREDITATION/CREDIT DESIGNATION STATEMENT

Physicians’ Education Resource®, LLC is approved by the California Board of Registered Nursing,Provider #16669 for 1.25 Contact Hour.
 
DISCLOSURES/RESOLUTION OF COI

It is the policy of Physicians’ Education Resource®, LLC (PER®) to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER® has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial interests pertaining to this activity.
METHOD OF PARTICIPATION
  1. Read the articles in this section in its entirety.
  2. Go to www.gotoper.com/go/ONN16Aug
  3. Complete and submit the CE posttest and activity evaluation.
  4. Print your CE Certificate.
OFF-LABEL DISCLOSURE/DISCLAIMER

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other healthcare provider relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®.

Lung Cancer

Web-Based System Boosts Survival in Lung Cancer

Anita T. Shaffer

Patients with lung cancer who participated in a web-based system for reporting and tracking their symptoms achieved dramatic gains in survival compared with individuals who were followed with typical protocols, according to study results presented at the 2016 ASCO Annual Meeting. Abstract LBA9006

The MoovCare system made a difference for patients because it resulted in early detection of dangerous conditions or recurrences, resulting in healthier individuals who were better able to undergo optimal therapy and earlier supportive care that improved quality of life, according to lead study author, Fabrice Denis, MD, PhD.

The median overall survival (OS) rate for patients who used the MoovCare system was 19 months compared with 12 months for participants in the control group after 20 months of follow-up. Additionally, 75% of the patients followed through MoovCare were still alive at 1 year versus 49% with standard procedures.

There also was a 50% reduction in the average number of imaging tests per patient per year with the use of the app, said Denis, a researcher at the Institut Inter-regional de Cancérologie Jean Bernard in Le Mans, France. These improvements were achieved even though the relapse rates were 
similar for both groups—49% among those who used the app and 51% among those with typical follow-up, researchers reported.

However, performance scores stayed higher among patients who used MoovCare. As a result, 74% of these patients were able to undergo optimal therapy upon relapse compared with 33% who had not used the app.

Denis said the need for an app in lung cancer is particularly pressing. “There are no standard follow-ups to detect relapse in patients,” he said. “Relapses are frequent and often symptomatic … Symptomatic patients often wait, leading to health degradation and nonoptimal therapy.”

MoovCare consists of a software application that patients or their caregiver use to report their symptoms. The algorithm analyzes the information for signals of potential relapse or complications and, if necessary, notifies the oncology care provider via email. The app can be accessed on mobile and desktop devices.

Denis and colleagues tested the system in a phase III trial conducted at 5 medical centers in France.

Results were reported for 121 patients in the intent-to-treat analysis who were randomized to use either the MoovCare system (n = 60) or routine follow-up (n = 61). The trial was stopped 
early at the interim analysis because of the positive results.

The study population consisted of patients with nonprogressive non–small cell lung cancer or small cell lung cancer at stages IIA through IV. Participants were required to have a performance score of 0-2 and a symptomatic score <7. All patients underwent chemotherapy before starting the trial and were permitted to continue tyrosine kinase inhibitor therapy or maintenance therapy throughout the study.

Patients in the MoovCare arm were required to self-report weekly for 12 clinical symptoms including asthenia, cough, dyspnea, and anorexia. Those with stage II-IIIA cancers also received CT scans at 6-, 12-, and 24-month intervals while those with stage IIIB-IV cancers were scheduled for scans at 12 months and 24 months.

In the control arm, patients with stage II- IIIA cancers received scans every 6 months, while participants with stage IIIB-IV disease were scheduled for monthly scans starting at 3 months.

Additional CT scans could be performed at the investigator’s discretion for patients in both arms, Denis said. The primary endpoint for the trial was OS with the boundary for superiority set at P <.006. Secondary outcomes included performance score evaluation after first relapse, progression-free survival, and quality-of-life score using the standard FACT-L, FACT-G, and TOI questionnaires.

In response to questions about MoovCare’s practicality, Denis said the system is easy to install on a computer and would simply require a doctor or nurse to monitor the emails.

However, Patricia Ganz, MD, said drawing benefit from such a system would necessitate changes in US practices. She said that similar experiments in the United States had found that information patients submit electronically does not generate action because of the cost of deploying personnel to monitor the data.

“We’re trying to restructure how we deliver care so that we can be responsive to these kinds of changes and these tools where patients can report their symptoms and how they’re doing on a regular basis,” said Ganz, an ASCO expert and professor at the UCLA Fielding School of Public Health/Department of Health Policy and Management:

“If there’s staff in the office who can respond [it would] really make a difference in preventing emergency room visits, hospitalizations, and so forth.”

Gregory A. Masters, MD, an ASCO expert and lung cancer specialist at the Helen F. Graham Cancer Center in Delaware, said the MoovCare system presents “one way to engage patients and allow them to take a more active role in their care.”

“Lung cancer is a unique cancer in some ways because many of these patients have a lot of guilt about their diagnosis,” added Masters. “I think we see that more in lung cancer patients than in many other patients. Some patients don’t want to bother the doctor or the nurse or the healthcare team with their symptoms or they think [their symptoms] are not important.”

 Nurse Perspective  
Betsy Hullender Quinn, MSN, MA, RN, OCN
Betsy Hullender Quinn, MSN, MA, RN, OCN
Thoracic Oncology Program Coordinator
Thoracic Oncology Nurse Navigator
Memorial Health Care System
Chattanooga, TN
 
“There’s an app for that,” seems to be forever ingrained in our collective psyche after years of hearing that phrase. Every facet of our lives seems to have an app that can track what we eat, how much we sleep, how much we spend ,and so forth.

The MoovCare web-based system, trialed in France, offers an app for increased survival in patients with stage II-IV lung cancer. Patients or their caregivers must chronicle the development of symptoms which could be a precursor to a recurrence of the disease. Symptoms such as weakness, increased cough, and shortness of breath are self-reported and are examined using an algorithm by the healthcare providers.    

The objective is to have patients who are hopefully healthier with a better performance score at the time of recurrence. With the reporting of symptoms using the MoovCare app and use of the algorithm by the provider, denial or ignorance of symptoms by the patient could be decreased. The result would be more timely and appropriate treatment.

Considering the favorable statistics in this relatively small study, the use of this technology could become a best practice in oncology; however, a few very large hurdles stand in the way.

Many of the patients that I see as a thoracic oncology nurse navigator are not tech-savvy. I hear this frequently, “I don’t know how to work my phone; I’ll have to have my children/grandchildren program it for me.” I would surmise that overcoming the fear of using this technology would be a major stumbling block for many patients with lung cancer.

Second, providing the staff to monitor incoming patient information can be expensive to the facility, whether it is a physician’s office or a hospital. Trained staff must be able to disseminate the information to the proper provider in good time. In this budget-minded healthcare world where the staff is already overworked and overextended, who will pick up the extra work?

The world of healthcare technology is rapidly changing every day, ultimately moving us toward better outcomes for our patients. Early symptom management can certainly mean being better stewards of our fiscal resources as well as being the right thing to do for our patients.  

Breast Cancer

Steroid Mouthwash Reduces Rate and Severity of mTOR Inhibitor-Associated Stomatits

Lauren M. Green.

A study of women treated with the mTOR inhibitor everolimus plus exemestane for their advanced breast cancer found that daily use of a steroid-based mouthwash markedly decreased the incidence and severity of stomatitis, and the researchers recommend that this preventive regimen become standard of care in this setting. The findings were reported at the 2016 ASCO Annual Meeting. Abstract 525

The trial known as SWISH found that after 8 weeks of using the mouthwash 4 times daily, incidence of grade ≥2 stomatitis was 2.4%, and stomatitis of all grades was 21.2%, compared with 33% and 67% of patients, respectively, in the comparator BOLERO-2 trial who did not use the mouthwash. That trial examined efficacy of the everolimus/exemestane (EVE/EXE) combination in patients with HR-positive, HER2-negative metastatic disease.

Lead investigator Hope S. Rugo, MD, described the SWISH findings as “very encouraging,” adding that the women who used the mouthwash tolerated it very well.

“There was a lot of concern about quality of life in these [BOLERO-2] patients. The other toxicities from everolimus are relatively easy to manage or uncommon,” explained Rugo in an interview at ASCO. Rugo is professor of Medicine and director of the Breast Oncology Clinical Trials Program at the UCSF Hellen Diller Family Comprehensive Cancer Center.

“Stomatitis is really the big issue, and almost all stomatitis occurs in the first 8 weeks.”

Against that backdrop, investigators sought to determine whether prophylactic use of a commercially available, alcohol-free, steroid-based mouthwash would prevent or ease the severity of this painful, treatment-related adverse event which can interfere with eating and lead to treatment disruptions.

The multicenter, single-arm, phase II SWISH prevention trial followed 86 postmenopausal women receiving the EVE/EXE combination daily for their HR+, HER2- advanced breast cancer. Women with existing stomatitis, oral mucositis, or mouth ulcers were excluded from the study.

Participants were instructed to use 10 mL of a commercially available, alcohol-free dexamethasone oral solution (0.5 mg/5mL; Roxane Pharmaceuticals) 4 times daily, and to swish it for 2 minutes before spitting it out. They were given a timer and instructed to take nothing by mouth for 1 hour after administration.

The mouthwash regimen was begun on day 1 of each 28-day EVE/EXE treatment cycle, for a minimum of 2 cycles. Participants filled out daily diaries to record their dietary intake and oral pain levels and also received education about the importance of good oral hygiene, including proper teeth brushing, flossing, and continuing their routine dental care.

Researchers reported that preventive use of the dexamethasone mouthwash “resulted in a greater than 10-fold reduction in the incidence of grade ≥2 stomatitis compared with BOLERO-2 patients.” Of the 2 patients in the mouthwash group who developed ≥2 stomatitis, the adverse event resolved to grade ≤1 after 11 days in 1 patient and 15 days in the other.

“We were really encouraged by this, and I think it is a new standard of care for patients who are taking everolimus,” said Rugo. “If you use the steroid mouthwash up front, you can prevent significant stomatitis—reducing the rate, and also the severity.”

Laura Guerra, RN, CCRC, Research Department Manager with Oncology Consultants in Houston, Texas, explained that stomatitis can be very debilitating for patients who experience it. She noted in an interview with Oncology Nursing News at the ASCO meeting that the stomatitis seen in the BOLERO-2 trial “was different from what we usually see, in that the sores tended to be deep sores with some pain. The condition can affect not only nutrition, but also interfere with delivery of the medication, as patients have to swallow it.”

She explained that before this intervention, many patients on the BOLERO-2 trial had to interrupt their treatment due to stomatitis, and thus wouldn’t get the full benefit of their regimen.

“If we can minimize or reduce these toxicities, patients will be more compliant with taking their anticancer medications, and it’s well known that when patients take their medication the way they’re supposed to, they’ll have better outcomes.”

For patients who continue to have clinical efficacy with everolimus, Rugo said that they can use the mouthwash as needed. If the mouth sores stop or taper off, they can stop using the mouthwash, but if they recur, patients can resume the mouthwash. “A lot of our patients did continue with it,” she added, with some reducing the frequency of the mouthwash to, for example, 3 times per day.

“What [this intervention] does for patients is to make the treatment more tolerable, regardless of what efficacy they eventually achieve. That’s our goal in the treatment of breast cancer, and certainly in the treatment of metastatic breast cancer—to achieve the therapeutic efficacy with less toxicity.”

Rugo said that the dexamethasone mouthwash represents a very cost-effective option to avoid this often dose-limiting toxicity. “I do think this is ready to integrate into practice now.”
Head and Neck Cancer

Individualizing Care for Elderly Patients With Localized Head and Neck Cancer

Lauren M. Green

Although paradigms for treating older patients with head and neck cancer are not well defined, advancements in targeted and immunotherapies and less toxic radiation regimens suggest that clinicians can aim for a more individualized approach to treating this patient population.

“One can speculate that we can push the boundaries of treatment,” argued Sandro V. Porceddu, MD, in his presentation during an education session at the 2016 ASCO Annual Meeting focused on challenging cases in the management of head and neck cancer (HNC).

Porceddu, who directs the radiation oncology research program at Princess Alexandria Hospital in Australia, said that making appropriate treatment decisions for elderly patients means going beyond statistical models of life expectancy and factoring into the calculation the patient’s comorbidities, functional status, social support, and treatment preferences.

Validated prognostic tools to assess comorbidities are easy to use and accessible, he noted, and include the Adult Comorbidity Evaluation 27 (ACE-27), the Cumulative Illness Rating Scale (CIRS), eprognosis.org, and the one he prefers, the Charlson Comorbidity Index (CCI).

He stressed that a patient’s functional status should be assessed independent of comorbidity: “These are two separate issues,” and functional status should involve not only patient/caregiver report of ability to perform activities of daily living (ADL), but also clinician-administered performance measures, such as assessing the patient’s gait speed with a tool like the Timed Up and Go (TUG) which he uses in his own practice.

And, finally, he added, “We know that social support is a significant predictor of morbidity in older patients.”

Definitions of the elderly differ, but the National Institute of Aging of the NIH has settled on the “young” old (65-74 years), “older” old (75-85 years), and “oldest” old (>85 years). For optimum clinical management of locally advanced squamous cell head and neck cancer (LAHNSCC), however, Porceddu said, “What we really need for planning treatment strategy are categories based on biologic age and tolerance,” which he has defined as “fit,” “intermediate,” and “frail” elderly patients.

For the fit old, clinicians can aim for standard of care, he said, and limited evidence exists in the research literature to support that choice. Elderly HNC patients are underrepresented in clinical trials, and there is currently no supportive evidence for treatment decision making for the intermediate old patient. Porceddu said these patients should be offered some compromise on standard of care. For the frail older patient, supportive care and symptom control is warranted: “The reality is, we probably don’t need any supportive evidence to make that decision for that group.”

Thus, oncology practitioners need to differentiate between patients who are simply elderly and those who are frail to customize their treatment and optimize patient outcomes. Porceddu shared with his audience one of his own cases to illustrate the point [Case Study].

As the incidence of HPV-associated oropharyngeal cancers increases and overall demographic trends point to more elderly patients being diagnosed with cancer, oncology practitioners can expect to see more older patients with LAHNSCC in the clinic. Porceddu stressed that advanced age alone should not be a contraindication to effective treatment:

“While treatment tolerance may differ compared with the young, there is a lack of high- level evidence that in the elderly, tumors respond differently, cancer-specific survival outcomes differ, and toxicity rates are worse.”

Reference
Porceddu SV. Management of elderly and infirm patients with locoregionally confined head and neck cancer: different strategies based on performance status and organ function. Presented at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.

CASE STUDY
Description: This 70-year-old man and former smoker presented with a painless neck lump. His smoking history was equivalent to >20 pack/ years, and he stopped smoking 10 years prior to diagnosis. He also had a significant past history of heavy alcohol intake (>10 years) and prior treatment for cirrhosis of the liver and hepatocellular carcinoma.

The patient was not experiencing dysphagia, weight loss, voice change, symptoms of aspiration, or problems with organ function. His ECOG status was 2, and his ability to perform activities of daily living (ADL) was good. Though he was not able to drive (a measure of instrumental ADL), he had a healthy and supportive partner.

Diagnostic testing revealed a stage T2N2bM0, left, 4-cm, hypopharyngeal, p16-negative, moderately differentiated locally advanced head and neck squamous cell carcinoma. His hepatology specialist anticipated that the patient would develop further HCC in about 18-24 months. The patient and his wife wanted to pursue curative but nonsurgical active treatment and avoid a long course of chemoradiotherapy. The patient’s 2-year survival was estimated at 35% based on the Charlson Comorbidity Index.

Discussion: “We weren’t confident he could tolerate a course of radical chemoradiation (70 Gy over 7 weeks plus high-dose cisplatin),” explained Sandro V. Porceddu, MD, due to his comorbidities and functional status, but he was not unwell enough for simply palliative treatment. Porceddu said that the patients needed a treatment plan that was less aggressive but would provide a balance between tumor control, toxicity, treatment compliance, and preservation of quality of life.

Porceddu and colleagues decided on a regimen involving radical concurrent chemoradiation (55 Gy in 25 fractions over 5 weeks) with concurrent, weekly cisplatin dosed at 40 mg/m2.

The patient experienced grade 2 dermatitis and grade 3 mucositis and required a nasogastric tube during the final week of treatment; however, these issues resolved.

After 6 months of uninterrupted treatment, the patient remained disease-free, with stable weight, continued ECOG status of 2, and able to continue ADL with help from his wife.

Supportive Care

Frozen Gloves and Socks May Relieve Chemotherapy-Induced Peripheral Neuropathy

Andrew J. Roth

Results of a small study exploring the use of frozen gloves and socks in women receiving paclitaxel chemotherapy for their breast cancer suggest the approach may hold promise for the relief of chemotherapy-induced peripheral neuropathy (CIPN). Abstract 10022

CIPN can occur in as many as three-quarters of patients undergoing treatment with paclitaxel chemotherapy and can persist for a full year in up to 80% of those patients. Further, CIPN can cause dose delays, dose reductions, or treatment discontinuation in nearly 25% of patients.

“Paclitaxel is a key drug for breast cancer management. It is a standard chemotherapy for adjuvant and also the metastatic setting,” explained study author Hiroshi Ishiguro.

“However, there is also a significant toxicity—peripheral neuropathy—which is very common, and when it occurs, it can sometimes last for many years.”

Ishiguro and his colleagues at Kyoto University in Japan, where he is senior lecturer with the Graduate School of Medicine, found that with the addition of frozen gloves and socks during treatment, objectively assessed CIPN was reduced from 81% to 28% in the hands and 64% to 25% in the feet of patients with breast cancer. The study involved 36 patients. Gloves and socks are stored inside a freezer set at –22 degrees Fahrenheit for more than 3 hours, typically overnight. A previous study by Ishiguro demonstrated that the degree of freezing does not alter the efficacy of the gloves in preventing chemotherapy-induced nail toxicity in patients with breast cancer.

Patients were included if they were treated with weekly paclitaxel chemotherapy for at least 12 cycles. Gloves and socks were worn for 15 minutes during the pre-medication period, for the entirety of the 60-minute chemotherapy infusion, and then for 15 minutes post-medication. Frozen gloves and socks were replaced halfway through.

Each of the patients wore a frozen glove and sock on their dominant hand and foot, and their nondominant side acted as the control. No patients dropped out because of cold intolerance.

The research team was primarily interested in objective incidence of any-grade CIPN as asses- sed by the Semmes–Weinstein monofilament test, but also evaluated patient-reported symptoms using a questionnaire. Further, researchers monitored changes to small nerves using thermal threshold testing and “manipulative dexterity” using the “grooved pegboard test.” Patients were evaluated before each of the 12 cycles of chemotherapy. Objectively assessed CIPN was significantly reduced from 81% to 28% in hands and 64% to 25% in feet. Incidence of patient-reported CIPN symptoms was also lower in hands (58% at baseline vs 8%) and feet (67% vs 19%).

In addition to the small study size, Ishiguro said limitations of the study were lack of blinding and randomization. Further, patients were not followed long-term after chemotherapy.

On their poster, Ishiguro and colleagues reviewed other methods of cryotherapy that have been previously studied and shown benefit: ice chips in the mouth to reduce fluorouracil-induced  mucositis, scalp cooling to reduce hair loss caused by chemotherapy, and cold packs over the eyes to reduce 5-FU-induced ocular toxicity.

Ishiguro said the gloves and socks cost about $80 each—he gets them at a discounted price— and that each patient uses 4 gloves and 4 socks. Though this adds up to $640 per patient, Ishiguro pointed out that the gloves and socks are reusable and called the method “very cost-effective.”

Prostate Cancer

More CNS Adverse Events With Enzalutamide Versus Abiraterone Plus Prednisone

John Otrompke

Patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated with enzalutamide were more likely to experience central nervous system (CNS) events or fatigue than patients treated with the combination of abira- terone acetate and prednisone. Further, patients treated with enzalutamide were more likely to reduce their treatment dose, according to results of research presented at the 2016 ASCO Annual Meeting. Abstract 5078

Researchers conducted a retrospective analysis of records contained in the Marketscan insurance claims database, identifying patients who were initially treated with either therapy after October 2012 and had at least 1 prostate cancer diagnosis.

Concerns regarding adverse events such as CNS conditions, fatigue, and pain potentially leading to dose reductions or treatment interruption are rising, according to the researchers.

Abiraterone acetate is an antigen biosynthesis inhibitor, while enzalutamide is an androgen receptor inhibitor. But both drugs come with side effects, especially fatigue and pain.

The researchers identified 2196 patients who had been prescribed abiraterone acetate, compared with 807 who had been prescribed enzalutamide. After the population data were reweighted, each group had approximately 1500 patients each.

The two treatment groups were then compared for CNS events such as fatigue and pain and relative dose intensity (80% or less or 85% or less), according to the researchers.

Differences in CNS events in the first 3 months lacked statistical significance, but at 12 months, the differences were statistically significant: 37.5% of those men taking enzalutamide experienced a CNS event, compared with 30.3% of men taking abiraterone acetate, according to the investigators.

Regarding fatigue, 28.6% of those on enzalutamide were impacted at 12 months, compared with 25% of those on abiraterone acetate.

Within 12 months, 24.4% of those on enzalutamide had a dose reduction to 85% or less of target dose, compared with 19.4% of those on abiraterone acetate.

Further, of those on enzalutamide, 20% had an even more drastic dose reduction to 80% or less of the target dose, compared with 13.6% of those on abiraterone acetate.

However, the difference as far as pain was not statistically significant, even at 12 months. In the enzalutamide group, 15.3% of patients experienced a pain event, compared with 12.9% of those who received abiraterone acetate.
Supportive Care

Walking and Resistance Training Eases CIPM, Especially Among Older Patients

Lauren M. Green

Patients undergoing chemotherapy who were prescribed a formal exercise program experienced less chemotherapy-induced peripheral neuropathy (CIPN), and the finding held true across all chemotherapy regimens tested. The effect was strongest in older patients, according to findings from a nationwide randomized controlled trial reported at the 2016 ASCO Annual Meeting. Abstract 10000

CIPN is a highly prevalent and severe side effect of certain chemotherapy types, such as platinums, taxanes, and vinca alkaloids, affecting more than 50% of patients receiving these therapies. Nevertheless, “there are currently no established treatments for CIPN—despite 50 randomized clinical trials—testing the efficacy of drugs to prevent or treat it,” explained lead study author Ian Kleckner, PhD.

Kleckner, a research assistant professor at the University of Rochester Medical Center, and colleagues performed a secondary analysis of a subset of 314 sedentary patients receiving taxane-, vinca alkaloid-, or platinum-based chemotherapy derived from a larger, phase III, national, randomized controlled trial (N = 619).

The majority of patients were women (92%), and 78% had breast cancer. They were randomized to chemotherapy alone or chemotherapy plus exercise. Patients randomized to the EXCAP arm (Exercise for Cancer Patients) which is a personalized, 6-week, home-based, moderate- intensity progressive program, were prescribed a daily walking regimen (eg, steps per day), supplied with pedometers, and also given a set of resistance bands to perform specific exercises.

Walking and resistance exercises were recommended for the control group. They did not receive any formalized support; however, control participants were given the exercise kit at the end of the study.

The investigators used patient self-report of tingling and numbness at baseline and after the intervention, rated on a 0-10 scale with 10 being the worst level of CIPN. In the EXCAP arm, CIPN was reduced compared with controls, with an effect size of 0.26 (P = .06), and the finding was independent of other variables, such as gender, BMI, and cancer stage. However, age was a moderating variable.

“We found that exercise was more effective for older patients,” said Kleckner. “Older patients in the control arm experienced a large increase in CIPN after 6 weeks of chemotherapy, whereas older patients in the experimental exercise arm had a very small, if any, increase in CIPN.”

Kleckner said that based on these findings, he and colleagues hope to expand their research. “What we’d like to do now is design a rando- mized clinical trial testing exercise against chemotherapy alone, where CIPN is the primary outcome. Only one trial to date has looked at this, and it was very small—60 patients.”

He hopes researchers can identify biomarkers in the brain circuitry or signals of the role inflammation may play to help better identify who is most at risk for CIPN.

Over the next few years, Kleckner would like to see this research continue to “scale up, so we can better learn about the effectiveness of exercise, understand what dose/intensity of exercise is important, what type of exercise, and who responds best to exercise…we’re hoping for an exercise prescription, instead of the generic ‘please exercise.’”
 Nurse Perspective  
Kristin Barber, RN, MSN, APRN
Kristin Barber, RN, MSN, APRN
Utah Cancer Specialists
Salt Lake City, Utah


For years we have had to manage the side effects of our chemotherapy treatments, and one of the most difficult has been chemotherapy-induced peripheral neuropathy (CIPN).  I reviewed both the NCCN Guidelines and the ONS Putting Evidence Into Practice, and both of these national databases either have no information to guide management of CIPN or have little evidence that has any likelihood of being effective. It is because of the lack of data available on CIPN that I welcome this research and hopefully more in the future.

The two studies reported at the ASCO meeting presented here give different approaches to management of CIPN. One approach uses cryotherapy with the application of frozen gloves and socks. Interestingly this modality was shown recently to have better supportive evidence for use in alopecia prevention in patients with breast cancer not receiving adriamycin. In the CIPN trial reported here, I believe they are three significant hurdles. First, their study population was unfortunately quite small at 36 patients. The second is the absence of blinding. This easily could contribute to falsely high subjective responses to the intervention. Lastly, in practice and in the study, the cost at $640 per patient is quite prohibitive and expensive for much of the population.

The second intervention looks at exercise for CIPN and has a larger study population of 314 patients. Unfortunately, in this study, their measurement tools were all subjective. Their data did prove to be positive and because this is a more practical and clinically useful way to approach CIPN, I could see using this approach in clinical practice. More research to identify the biologic reasons for improvement in CIPN, as well as a more precise exercise regimen, are avenues that would be useful to explore.

Colorectal Cancer

Tumor Location Linked to Survival Outcomes in Metastatic Colorectal Cancer

Jason M. Broderick

Survival outcomes in patients with KRAS wild-type metastatic colorectal cancer (mCRC) were significantly longer among those with tumors originating on the left versus the right side of the colon, according to a retrospective analysis of the phase III 80405 trial presented at the 2016 ASCO Annual Meeting. Abstract 3504

The median overall survival (OS) was nearly 14 months longer in patients with left-sided tumors, including a nearly 20-month survival advantage in patients receiving frontline cetuximab plus chemotherapy and an over 7-month survival benefit in patients receiving frontline bevacizumab plus chemotherapy.

The findings also indicated that tumor location may inform frontline targeted therapy selection in mCRC, with cetuximab inducing a greater benefit in patients with left-sided tumors, and those with tumors on the right side of the colon benefiting more from bevacizumab.

“The 14-month improved survival in left- versus right-sided primary tumors is really striking for patients who present with metastatic disease,” said lead study author Alan P. Venook, 
MD, a professor of Medicine at the University of California, San Francisco.

“Molecular analysis of these tissues is underway—certainly we believe that the side is a surrogate marker for a biologic explanation, and we’re hoping to tease that out over the next few months. Until we have sorted that out, colon cancer originating on the right side should be treated differently than colon cancer originating on the left side,” said Venook.

In the primary 80405 analysis, 1137 patients with treatment-naïve KRAS wild-type (codons 12 and 13) mCRC (performance status 0-1) were randomized in a 1:1 ratio to cetuximab (n = 578)  or bevacizumab (n = 559) plus physician’s choice of FOLFOX or FOLFIRI. Cetuximab was administered at an induction dose of 400 mg/m2 followed by 250 mg/m2 weekly, and patients received bevacizumab at 5 mg/kg every 2 weeks. Among all patients, 26.6% were treated with FOLFIRI and 73.4% received FOLFOX. Treatment was continued until curative surgery, disease progression, or unacceptable toxicity.

The results of the primary analysis presented at the 2014 ASCO Annual Meeting showed that there was no OS or progression-free survival (PFS) difference with bevacizumab or cetuximab. At a median follow-up of 24 months, OS was 29 months in the bevacizumab arm and 29.9 months in the cetuximab arm.

For the retrospective analysis, Venook et al identified the primary tumor location of all patients enrolled in the 80405 trial: right (293), left (732), transverse (66), and uncertain (46). The left side of the colon was defined as the descending colon, sigmoid colon, and rectum, and the right side included the cecum and ascending colon. The analysis Venook discussed compared the left and right populations, and excluded the transverse.

Across both treatment arms, the median OS was 19.4 months among patients with right- sided tumors compared with 33.3 months for patients with left-sided tumors. PFS was 8.9 versus 11.5 months, respectively.

Among patients who received cetuximab, the median OS was 16.7 months in patients with right-sided tumors versus 36 months in the left-sided cohort. PFS was 7.7 months versus 11.9 months, respectively.

The cetuximab outcomes are similar to a previously reported subgroup analysis from the phase III FIRE-3 trial, which compared FOLFIRI plus either bevacizumab or cetuximab in the frontline setting for KRAS wild-type mCRC. In a subgroup of 167 patients from FIRE-3, the median OS was 38.7 months in patients with left-sided tumors (n = 137) versus 16.1 months in patients with right-sided (n = 30) tumors.

“The [80405] data and other findings, both presented at ASCO meetings and in press, suggest that patients with right-sided primary metastatic colon cancer get little to no benefit from cetuximab,” said Venook.

Patients in study 80405 with right-sided tumors fared far better with bevacizumab compared with cetuximab. Among the bevacizumab cohort, OS was 24.2 months in the right-sided population versus 31.4 months in patients with left-sided tumors. PFS was 9.6 versus 11.1 months.

“This is the largest study to date of tumor location in colorectal cancer, and it suggests that this unexpected factor could answer some long-standing questions about why certain patients do better than others,” said ASCO President Julie M. Vose, MD.

“It is also an important reminder, in this exciting era of precision medicine, that genomics is not the only source of insight into how cancers should be studied and treated.”
 Nurse Perspective  
Laura Metcalfe, MSN, RN, APN-C, AOCNS
Laura Metcalfe, MSN, RN, APN-C, AOCNS
John Theurer Cancer Center
Hackensack, NJ

As I read this abstract, it occurred to me just how far we’ve come in treating metastatic colorectal cancer (mCRC). When I began in oncology 28 years ago, there was basically one treatment for colorectal cancer (adjuvant or metastatic): 5 FU and leucovorin. The addition of irinotecan and later oxaliplatin started to change the landscape in the late 1990s and early 2000s. Once the targeted therapies of bevacizumab (VEGF inhibitor) and cetuximab (EGFR inhibitor) were added, we started to see patients with mCRC often living years rather than months. In fact, we are currently continuing to treat a patient who was initially diagnosed with mCRC in 2007.

In the beginning, however, cetuximab was given to all patients with mCRC based on EGFR overexpression, as it was believed this was a predictor of response. This turned out to not be the case. We then learned about KRAS mutation, and discovered that patients with mutated KRAS (vs wild-type KRAS) did not benefit from cetuximab and that it could actually 
worsen their disease. It then became mandatory to do KRAS testing prior to cetuximab administration. However, even with that, we realized that only about 40% of patients with wild-type KRAS responded to cetuximab, so we knew there was more to the story.

More recently we’ve identified BRAF mutations which also confer resistance to the EGFR inhibitors. It is now standard practice to do “extended mutational analysis” or pan-RAS testing (not just KRAS testing) on all mCRC tumors in order to determine which therapies are most appropriate for our patients. The ultimate goal is personalized cancer therapy based on mutations found in an individual’s cancer, not just a “one size fits all” approach.

Unfortunately, at this moment some of these genomic profiles are identifying mutations for which there are no therapies or no approved therapies. Therefore, this idea of left- versus right-sided colon cancers responding differently to cetuximab, a readily available therapy, is intriguing and certainly warrants further study. Any knowledge which helps to inform treatment decisions and improve outcomes for our patients is always welcome.

While we have learned much about mCRC, there is still much more to be learned, reinforcing the need for ongoing clinical trials. As oncology nurses, we should encourage all of our patients to participate in clinical trials if they are eligible. That remains the best way to improve the treatment of not only of patients with colorectal cancer, but all patients with cancer.  

Palliative Care

Despite Recommendations, Aggressive Cancer Treatment Still Common at End of Life

Laura Panjwani

An analysis of more than 28,000 patients aged  <65 years with incurable cancers found that approximately three-fourths of them received aggressive care within the last 30 days of life and one-third died in the hospital. The findings were presented at the 2016 ASCO Annual Meeting. Abstract LBA 10033

The analysis, which included patients with 5 different types of metastatic cancer, also found that providing aggressive care at the end of life was not impacted by ASCO’s Choosing Wisely recommendations, issued in 2012, which strongly advised against cancer-directed therapy in patients with advanced solid tumors who are unlikely to benefit from it, instead encouraging a focus on symptom-directed palliative care.

“Aggressive medical care for patients with incurable cancers at the end of life is widely recognized to be harmful to patients and their families,” said Ronald C. Chen, MD, MPH, who presented the analysis at ASCO. “Additional efforts are critically needed to improve end-of-life care for patients with terminal disease to ensure that the care provided meets the goals and preferences of patients and their families.”

The study looked at data from large commercial insurance claims of patients in 14 states. Patients were aged <65 years, had metastatic cancer of the lung, breast, prostate, colon, or pancreas, and died between 2007 and 2014. The study examined 6 indicators of aggressive care at the end of life: chemotherapy, radiation, invasive procedures (eg, biopsy, surgery), emergency department visits/hospitalization, intensive care, and in-hospital death.

The most common form of aggressive care was hospital admission or emergency department visit, occurring in 65% of patients with lung or pancreatic cancer, 62% of patients with colorectal or prostate cancer, and 64% of patients with breast cancer. Incidence of each aggressive therapy was remarkably similar across all 5 cancer types, said Chen, and notably, fewer than that 1 in 5 patients in the study utilized hospice care.

Across all 5 cancers investigated during the last 30 days of life, chemotherapy rate ranged from approximately 24% to 33% of patients, invasive procedure rate (25% to 31%), and ICU care (16% to 21%).

Radiotherapy was the least utilized treatment at the end of life, and also the most inconsistently prescribed across cancer types. Rates of use ranged from approximately 6% in pancreatic cancer to 21% in lung cancer.

In addition, the study found that between 30% and 35% of patients across all 5 tumor types investigated, died in the hospital.

Study investigators also analyzed treatment trends before 2012 and between the first quarter of 2012 and the fourth quarter of 2014.

“The percentage of patients who received aggressive care over the last 30 days of life really didn’t change over time in these 5 cancers, said Chen. “We also saw little change before 2012, and the use of aggressive care did not seem to decrease after ASCO’s 2012 Choosing Wisely recommendations.”

While it is unclear exactly why the ASCO recommendations did not result in any changes, the bigger issue is why there are not more initiatives to improve end-of-life care overall, said Patricia Ganz, MD, FASCO, ASCO Expert in breast cancer.

“While Dr. Chen focused on Choosing Wisely in 2012, giving chemotherapy in the last 30 days of life has been a coping measure for a very long time, and it has been nationally looked at as one of our failures in giving good end-of-life care,” said Ganz.

It is most likely that end-of-life aggressive treatment is driven both by patients and their doctors, said Chen. Oncologists are not always aware or accepting that a patient is nearing the end of life, and they may be motivated to continue to treat the patient by a strong desire to help them, despite survival chances, said Chen.

However, the study also showed that twothirds of patients went to the emergency department or were admitted to the hospital at the end of their lives, suggesting that patients may also play an active role in the high rate of aggressive end of life treatment.

While it is ultimately up to a patient if he or she would like to continue receiving aggressive treatment at this stage, oncologists and oncology nurses need to do a better job of discussing patients’ wishes and educating them on their options, said Andrew Epstein, MD, ASCO Expert in palliative care.

“Education for any clinician, whether it is a physician a nurse, or others, is extremely important in order to improve their ability to have these very challenging conversations about the end of life and what is important to patients and their families,” said Epstein.

“We need to teach oncology professionals in order to make these very, very challenging conversations easier. We need to find out what is important to patients and their families and marry the care delivered to what they say is important.”

Palliative Care

Integrating Palliative Care Early Improves Outcomes for Caregivers

Andrew J. Roth

Early palliative care integrated with oncology care benefits not only patients with cancer but also family caregivers, according to phase III data presented at the 2016 ASCO Annual Meeting—the first study to show such an impact, according to the researchers. Abstract 10131

At a 12-week analysis, primary caregivers— a category that could include family members or friends—reported fewer depression symptoms and improved vitality and social functioning compared with caregivers of patients receiving strictly medical care. After 24 weeks, the lower rate of depression symptoms persisted, but no difference was observed in vitality and social functioning.

“We can now say that the benefits of early palliative care can extend beyond patient outcomes and can actually positively impact family caregivers,” said Areej El-Jawahri, MD, an oncologist from Massachusetts General Hospital Cancer Center who presented the trial findings at ASCO.

A total of 350 patients with newly diagnosed incurable lung or gastrointestinal cancers and 275 family caregivers were enrolled and randomized to receive usual oncology care (n = 138) or usual care in addition to palliative care (n = 137).

In the palliative care visits, clinicians focused most on symptom management, coping, establishing rapport, and “illness understanding.” The most common symptoms addressed were pain and fatigue, while the most common coping topics addressed were redirecting hope, coping counseling, and behavioral coping. Family caregivers were not required to attend palliative care sessions, El-Jawahri said, though more than 50% of them did.

Family caregivers’ quality of life and mood were measured using the Medical Outcomes Study Health Survey Short Form-36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS), respectively. Analyses were taken at baseline, 12 weeks, and 24 weeks. At the 12week assessment, family caregivers of patients in the intervention group reported higher vitality (1.1 vs –3.2) and social functioning (–3.0 vs –3.8), and fewer depression symptoms (–0.45 vs 0.24), respectively, when compared with their counterparts in the group receiving usual care alone.

During this assessment, “there were also non-significant improvements in other quality-of-life domains, such as bodily pain and physical-role functioning,” El-Jawahri said. At the 24-week assessment, family caregivers in the early palliative care group still had a lower rate of depression symptoms (-0.37 vs 0.28), but no differences were observed in vitality or social functioning compared with the control group.

El-Jawahri pointed out that improvement in family caregiver outcomes seemed to be “at least partially mediated” by improvement in patients’ quality of life.

The importance of palliative care—both early and otherwise—has been well studied, she added. “We do know that the integration of palliative care can improve quality of life and mood in patients with advanced cancer,” El-Jawahri said, emphasizing that early palliative care can even have a positive impact on outcomes for patients. Palliative care, which El-Jawahri defined as care given by a multidisciplinary team of doctors, nurses, social workers, and psychologists, can provide an “extra layer of support” for patients.

ASCO president Julie M. Vose, MD, MBA,  FASCO, echoed this sentiment and reinforced the importance of this study’s findings.

“This study really points out that we have so many ways to help our patients and their families through their treatment,” said Vose. “Early palliative care is not only going to help the patient, but also help the family and the caregivers to get the patient through treatment with an improvement in their quality of life.”
 Nurse Perspective  
Anne-Marie Shaftic, RN, NP-C, AOCNP
Anne-Marie Shaftic, RN, NP-C, AOCNP
Nurse-Practitioner, Oncology
Holy Name Hospital
Teaneck, NJ


As oncology nurses, we often wonder why patients are not referred to palliative care teams in the early stages of cancer. Early interventions with a palliative care team can greatly improve both patient and caregiver satisfaction. One strategy that may improve patient referral to palliative care services is to raise awareness of what palliative care services entail.

Palliative care is the management or relieving of any form of distress experienced by the oncology patient and caregivers. The team is an interdisciplinary group that typically includes the oncologist, primary care practitioners, nurse practitioners, oncology nurses, and social workers all striving to relieve pain and suffering that a patient may be experiencing.

Although palliative care is aimed at caring for the patient, it also assists the caregiver with some of the burden of care. Caregivers often face many responsibilities, such as scheduling appointments and managing the patient’s symptoms, and many also need to maintain their own employment to provide an income. This increases stress and fatigue, often making caregivers feel inadequate that they cannot provide enough time or care to the patient and lead to feelings of depression and social isolation.

Findings from this study by Areej El-Jawahri, MD suggest that the early provision of palliative care positively affects caregivers, too. In this study, 275 family caregivers were randomized to receive routine care with or without palliative care, and caregivers in the palliative care arm were found to have less depression, improved energy, and less social isolation.

Oncology nurses are advocates for our patients and their families. We offer support to both patient and family and are well-positioned to educate the patient and family on the role of palliative care to promote better outcomes throughout the cancer experience.

Oncology nurses start palliative care from the moment the patient is diagnosed, offering support, nurturing, and comfort. Nurses need to stand together and offer these services to patients and their caregivers, and as we move forward, all oncology practitioners need to become more comfortable with discussing options for palliative care
Precision Medicine

Outcomes Better With Biomarker-Based Therapies in Phase I Studies

Silas Inman

Outcomes were significantly better in clinical trials that utilized a biomarker based treatment selection strategy compared with non-personalized approaches, according to a meta-analysis of 13,203 patients from phase I trials presented at the 2016 ASCO Annual Meeting. Abstract 11520

In the analysis, there was a response rate of 31% in the biomarker-driven arm compared with just 5% in the non-personalized group. The median progression-free survival (PFS) in the biomarker arm was 5.7 months compared with 3 months without biomarker selection. Findings from the study could reshape the intent behind early-phase clinical trials, according to the  researchers.

“In the past, it was heard that phase I trials were not about efficacy, and their only purpose was to understand side effects,” lead investigator Maria Schwaederle, PharmD, Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, reported. “Our analysis really showed that this belief is completely outdated, and with biomarker selection, and especially genomic biomarkers, we can reach high response rates even in phase I trials.”

For the analysis, findings from 351 single- agent phase I study arms were selected from the PubMed index between January 2011 and December 2013. For the purpose of the study, personalized therapy was defined as a treatment that was selected using a biomarker test or a trial conducted in a population in which at least 50% of individuals harbored a known biomarker.The analysis focused exclusively on response rates and PFS. Overall survival was not explored, since this information was rarely reported from these early-phase studies. Response rates were available for all 13,203 patients from 58 biomarkerdriven trials and 293 non-personalized trials. PFS data were only available for 1700 patients from 7 biomarker trials and 38 standard trials.

Targeted therapies that were utilized in the absence of a biomarker test demonstrated low response rates that were similar to clinical trials exploring cytotoxic agents. In the non–biomarker driven targeted therapy trials (n = 177), the response rate was 5.1% versus 31.1% in those treated with a biomarker-based targeted therapy (n = 57).

“Targeted drugs in and of themselves were not effective. They absolutely need to be given to the right patients,” said Schwaederle. “A biomarker-based approach was the most significant independent predictor of improved outcomes in phase I studies.”

Certain types of biomarkers were associated with even higher response rates for patients treated using personalized approaches. Those selected for therapy using a genomic biomarker had a response rate of 42% versus 22.4% in those selected using protein expression.

“Both genomic and protein biomarkers led to improved outcomes, but genomic biomarkers performed better,” said Schwaederle. “Indeed, the response rate in this heavily refractory popula- tion was over 40% with the use of a genomic biomarker.”

In recent years, there has been an increasing trend toward accelerated FDA approvals based upon early findings from phase I studies. An early example of this success was illustrated in the approval of crizotinib, which was based on early-phase studies for patients with ALK- rearranged non–small cell lung cancer (NSCLC). One of these instrumental studies was included in the analysis, according to Schwaederle.

In this phase I study, 119 patients with ALK- rearranged NSCLC received crizotinib. The response rate was 61%, which included 2 complete responses. The median duration of response was 48.1 weeks.

Other examples of success seen with targeted therapies included BRAF inhibition for patients with BRAF-mutant metastatic melanoma and imatinib for BCR-ABL chronic myelogenous leukemia. For the time frame of the study, studies exploring BRAF inhibitors were explored as well as second-generation BCR-ABL inhibitors, such as dasatinib, Schwaederle explained. All of these agents have gone on to gain FDA approval.

“Precision medicine is not the future of cancer care, it is the present,” said ASCO spokesperson, Don S. Dizon, MD, who moderated the panel where the study results were presented. “This study reinforces that the more we personalize treatment to the patient and the tumor, the better the outcomes—even in the earliest phases of research.”
 Nurse Perspective  
David Leos, RN, MHA, OCN, CBCN
David Leos, RN, MBA, OCN
Manager, Clinical Protocal Administration
Department of Plastic Surgery
The University of Texas MD Anderson Cancer Center
Houston, TX


Times have changed in clinical trials. This study points to what could well represent a transition in how early-phase clinical trials are conducted. For perhaps as long as there have been laments over the lack of effective agents for refractory malignancies or the dismal rate of enrollment in clinical trials, there have also been few changes in the way such treatments are evaluated.

Except for the introduction of adaptive trial design, which changes treatment allocations according to assigned treatments of patients already on the same trial, little has changed. Nurses have been taught and then teach patients that the intent behind phase I studies is to determine dose-limiting toxicities and caution them that deriving personal therapeutic benefit should not be part of their expectations.

This meta-analysis appears to have included results of trials that fall under the relatively new category of basket trials which use the same treatment agent on genetic alterations that are the same among different tumor types.

The term umbrella trials is also new and describes trials which focus on the same tumor histology and treat each based on identified individual genetic alterations. It remains to be seen what the full impact of these response rates will have on practice. However, the publicity about this meta-analysis along with reports on basket and umbrella trials with precision agents, such as the Lung-MAP and NCI-Match studies, have created a buzz about how this approach will change the way and speed at which trials are conducted.

Surely there’s a place for the efficiencies demonstrated in such trials with biomarker-based treatment selection strategies. These types of trials could play a key role in the National Cancer Moonshot effort and could be considered in the context of a reimagined “5 rights of medication administration”: the right biotherapy for the right patient.

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