Clinical Insights: February 2018

Thursday, February 22, 2018

Release Date: February 22, 2018
Expiration Date: February 22, 2019


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 participate 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 1.0 Contact Hours.
 
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 Go to www.gotoper.com/go/onn18february
  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®.

Adverse Effects

Direct Oral Anticoagulant Prevents VTE Recurrence in Select Patients

Kristie L. Kahl

Treatment using oral rivaroxaban (Xarelto) reduced venous thromboem-bolism (VTE) recurrence among patients with cancer, according to results from the select-d trial. Study results, presented at the 2017 American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, also showed an increase in clinically relevant nonmajor bleeds (CRNMBs) among patients treated with rivaroxaban, suggesting this regimen may be a safe and beneficial alternative in select patients.

Dalteparin (Fragmin), a low molecular weight heparin, is the standard of care for extended treatment and prevention of acute VTE recurrence in patients with cancer. Rivaroxaban, a direct oral anticoagulant (DOAC), is a highly selective direct Factor Xa inhibitor with oral bioavailability and may offer another treatment option.

Researchers from Warwick Medical School of the University of Warwick in Coventry, United Kingdom, conducted the prospective, randomized, open-label, multicenter pilot trial to compare dalteparin, administered subcutaneously, with rivaroxaban treating VTE in 406 patients with cancer, including those with symptomatic or incidental pulmonary embolism (iPE) or symptomatic lower-extremity proximal deep vein thrombosis (DVT).

In month 1, patients in the dalteparin arm received 200 IU/kg daily followed by 150 IU/kg in months 2 through 6. Patients in the rivaroxaban arm were administered 15 mg twice daily for 3 weeks, followed by 20 mg once daily for 6 months. After 6 months of trial treatment, DVT patients who were residual vein thrombosis (RVT)–positive and patients with PE at presentation could be randomized to placebo or rivaroxaban for an additional 6 months.

The initial randomization included 530 patients, of which 150 remained in each arm of the second randomization to assess the duration of anticoagulation. The trial sample size was reduced when the second randomization closed due to a high attrition rate.

A revised sample size of 203 patients in each arm was used to evaluate the trial’s primary endpoint of VTE recurrence. Secondary endpoints included major bleeds and CRNMBs—including overt bleeds resulting in unscheduled contact with a physician or interruption or discontinuation of study drug—acceptability, survival, and health economics.

Patients were a median age of 67 years, of which more than half were males (53%) and most were white (95%). They presented with either early or locally advanced disease (n = 156; 38%), metastatic disease (n = 240; 59%), or hematologic malignancies (n = 10; 3%). Patients also presented with iPE (n = 214; 53%) or had symptomatic PE or DVT (n = 192; 47%). Of the 280 patients receiving anticancer treatment at the time of the VTE, most were getting chemotherapy (n = 232; 83%) or targeted therapy (n = 41; 15%).

The rivaroxaban arm (4%; 95% CI, 2-9%) induced lower rates of VTE recurrence compared with the dalteparin arm (11%; 95% CI, 7-17%). Major bleeds appeared similar between arms, with 6 bleeds in 6 patients who received dalteparin (3%; 95% CI, 1-6%) and 9 bleeds in 8 patients who received rivaroxaban (4%; 95% CI, 2-8%).

However, more CRNMBs occurred in the rivaroxaban arm, totaling 28 bleeds in 27 patients (13%; 95% CI, 9-19%) compared with 5 bleeds in 5 patients who received dalteparin (2%; 95% CI, 1-6%). Overall, 11 patients (5%; 95% CI, 3-9%) in the dalteparin arm had bleeds categorized as either major bleeds or CRNMBs compared with 34 patients (17%; 95% CI, 12-22%) in the rivaroxaban arm.

The researchers are conducting further analyses to determine the factors that may have contributed to this difference, according to a press release.

In addition, 208 patients completed 6 months of treatment, including 100 who received dalteparin (52%) and 108 who were on rivaroxaban (55%). At 6 months, the rivaroxaban arm (74%; 95% CI, 68-80%) demonstrated superior overall survival compared with the dalteparin arm (70%; 95% CI, 63-76%).

In the second randomization, only 92 patients of the required 300 were recruited, including 82 PEs and 10 DVTs. Patients did not continue to the second randomization as a result of death or withdrawal (50%), being RVT-negative (12%), failing the other eligibility criteria (24%), or declining to participate in randomization (14%).

REFERENCE

Young A, Marshall A, Thirlwall J, et al. Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism: results of the select-d pilot trial. Presented at: 2017 ASH Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA. Abstract 625.  
 
Brain Cancer

Patients With High-Grade Gliomas Don’t Get Adequate Access to Palliative Care

Beth Fand Incollingo

There’s a delicate balance to providing palliative care to people with high-grade gliomas.

Quality-of-life care has benefits from the outset for these patients, but because some might confuse it with end-of-life support, neuro-oncologists may hesitate to introduce it.

An Australian healthcare team recognized that dilemma and responded by creating a standardized policy for introducing palliative care to patients with high-grade gliomas. The guideline is meant to ensure that patients get palliation of their physical and emotional symptoms without becoming convinced that their health is failing, said Professor Jennifer Philip, chair of palliative medicine at St. Vincent’s Hospital at the University of Melbourne. She hopes the guideline will be widely adopted after it undergoes further study.

“If it’s embedded [in the system], it does not make the patient feel singled out,” she said of palliative care, adding that the guideline negates the need for doctors to second-guess their timing for introducing this type of treatment.

Palliative care can help alleviate physical symptoms or adverse effects, ease difficult emotions and anxiety, resolve worrisome questions, and even prolong life. It’s crucial for people with high-grade gliomas, Philip said, because they are more likely to experience sudden, unexpected health setbacks or cognitive declines than are patients who have other types of cancers.

“Communication is very important,” Philip said. “It happens at diagnosis and often not after that, but people want to know what to do about seizures before they happen, and there are huge physical needs. [Caregivers] have needs, too, because they tell us that bizarre things happen. There are behavioral changes; the patient lacks insight, [caregivers] don’t know why it’s happening, and healthcare may not recognize it.”

That’s why barriers to palliative care need to be removed, particularly while patients are well enough to engage in decisions about their care, Philip said. Her model aims to do that by standardizing referrals, so both patients and doctors expect it to be part of treatment and know when it should be offered.

The Information, Coordination, Preparation, and Emotional support model suggests that these interventions span a patient’s whole experience with high-grade glioma. It calls for regular communication about palliative care, including routine monitoring and screening of patient and family needs, as well as proactive responses to anticipated concerns. The set of guidelines suggest starting specific initiatives according to disease stage or transition points, as well as coordination of all these efforts.

A phase II pilot study of the program included 32 patients, most with late-stage disease who had undergone surgery, and 31 caregivers. Participants reported a high level of completion of and satisfaction with the program, and healthcare practitioners found it useful, Philip reported.

The program was developed based on feedback from patients, caregivers, and healthcare professionals. It also incorporates the team’s review of scientific literature and analysis of epidemiological data about more than 1000 patients treated in Victoria, Australia, for high-grade glioma over several years. Using those data, a multidisciplinary advisory committee framed the recommendations. “Our goal is to build it as a routine part of cancer care for this group,” Philip said.

The panel discussion was chaired by Tobias Walbert, MD, PhD, MPH, director of neuro-oncology at the Hermelin Brain Tumor Center at Henry Ford Health System, in Detroit, Michigan. He agreed that palliative care, in parallel with medical treatment, should begin soon after diagnosis—especially in advanced cancers—to best ease patients’ pain, other physical discomforts, and psychosocial and spiritual concerns.

He clarified that palliative and hospice care have different aims, adding that they should be part of a continuum overseen by the same providers throughout so patients never feel abandoned.

Some challenges to that goal are that most neuro-oncology units are not set up to keep tabs on declines in patients’ conditions that could be eased by palliative care, Walbert said. He added that, when a patient is ready to transition to hospice, oncologists and palliative care specialists often find it difficult to have the necessary end-of-life discussions. Unfortunately, he said, this can mean that patients don’t benefit from hospice services as early as they should.

REFERENCE
1. Walbert T, Carver A, Philip J. Palliative care–health outcome measures and communication strategies in neuro-oncology. Panel discussion at: 22nd Annual Meeting and Education Day of the Society for Neuro-Oncology; November 17, 2017; San Francisco, CA.
 

Nurse Perspective

Darcy Burbage, RN, MSN, AOCN, CBCN Darcy Burbage, RN, MSN, AOCN, CBCN
Supportive and Palliative Care Nurse Navigator, Helen F. Graham Cancer Center and Research Institute, Newark, DE


High-grade gliomas are an aggressive form of brain cancer with a generally poor prognosis and long-term survival rate. Patients often suffer from significant neurocognitive symptoms, including personality changes, seizures, fatigue, depression, and anxiety. Because most patients lose decision-making capacity, advance care planning conversations early in the disease course are essential to elicit the patient’s wishes for end-of-life care. Additionally, effective communication with surrogate decision makers during all stages of the disease helps ensure that those wishes are respected. Many studies have shown that early integration of palliative care improves quality of life for individuals living with advanced cancer and their caregivers by providing expert symptom management and psychosocial support. However, not all providers or patients associate palliative care with managing symptoms but, instead, correlate it with end-of-life or hospice care.

Results of the panel discussion on the Information, Coordination, Preparation, and Emotional support (I-CoPE) model provide a great example of taking these concerns and turning them into an opportunity to directly improve patient care.

I-CoPE outlines palliative care interventions throughout the continuum of care for patients diagnosed with a high-grade glioma. These guidelines improve communication between the interdisciplinary team and patients as they describe the care that should be provided through transition points, as well as allow for ongoing coordination of care. Standardized evidence-based criteria were used to automatically trigger a palliative care consultation, allowing for a more objective assessment of the needs of the patient and family. Because these guidelines are embedded in the healthcare system, standardizing the care for individuals diagnosed with a high-grade glioma, it reduces the physician from second-guessing timing of referrals and reduces patients’ feelings that they are being singled out because of their diagnosis.

Although this set of guidelines was developed and implemented specifically for neuro-oncologists caring for individuals with high-grade gliomas, attention to clear, consistent communication and palliative care guidelines should be developed and incorporated into a future needs-based model of care for all patients.
 
Ovarian Cancer

PARP Inhibitors Bring Excitement to Ovarian Cancer Treatment

Tony Hagen

PARP inhibitors offer exciting opportunities to improve outcomes for patients with ovarian cancer and, hopefully— if evidence warrants—will move to the frontline setting, said Susana M. Campos, MD, a gynecologic oncologist at Dana-Farber Cancer Institute and an assistant professor at Harvard Medical School in Boston, Massachusetts.

“It’s important that we start to use these drugs more and more and bring them sooner into the management of the individual,” said Campos, who reviewed trial data and approvals for several PARP inhibitors and looked at the potential for advancing the use of these agents.

The Food and Drug Administration has approved various PARP inhibitors, which interfere with a tumor cell’s ability to make DNA strand repairs, for use following platinum therapy and for maintenance in the ovarian setting. Those include olaparib (Lynparza) for germline BRCA mutations (gBRCAm) following 3 prior lines of therapy, rucaparib (Rubraca) for gBRCAm and somatic BRCAm following 2 prior lines, and niraparib (Zejula) and olaparib for post-platinum maintenance.

Several trials are important for shedding light on PARP capabilities, Campos said, including NOVA, SOLO-2, STUDY 19, and ARIEL3.

The NOVA trial applied niraparib in platinum-sensitive, recurrent, high-grade serous carcinoma in patients previously treated with at least 4 cycles of a platinum-containing agent and results had showed a partial or complete response. Treatment dosage was 300 mg daily. In the gBRCAm cohort, the median progression-free survival (PFS) for niraparib was 21 months versus 5.5 months on placebo; in the non-gBRCAm homologous repair defect (HRD)-positive cohort, the median PFS was 12.9 and 3.8 months, respectively. In the overall non-gBRCAm group, the median PFS was 9.3 months on niraparib versus 3.9 months for placebo. “Niraparib improved PFS across all 3 groups—germline and nongermline,” Campos noted.

The SOLO-2 study was unique in that it accrued BRCA1 and BRCA2 mutation carriers only, she said. Patients had at least 2 prior lines of platinum therapy and demonstrated sensitivity to it. Dosage was 300 mg twice daily. The olaparib group (n = 196) had a median PFS of 19.1 months versus 5.5 months for those on placebo (HR, 0.30; 95% CI, 0.22-0.41; P <.0001).

STUDY 19 enrolled patients with platinum-sensitive, high-grade serous ovarian cancer and ≥2 previous platinum regimens. Of 265 recruited, 22% were BRCA-positive and 14% were BRCA-negative. The Olaparib dosage was 400 mg orally twice daily with treatment until disease progression. In the primary analysis, median PFS was 8.4 months for olaparib and 4.8 months for placebo (HR, 0.35; 95% CI, 0.25-0.49; P <.001). Campos noted that this study was particularly significant because it accepted all comers, whether they were BRCA carriers or not.

ARIEL3 was a phase III randomized trial of rucaparib versus placebo in patients with ovarian cancer who had responded to platinum therapy. In the BRCAm subgroup, median PFS was 16.6 months for rucaparib and 5.4 months for placebo; for patients in the HRD BRCA germline or somatic group, the median PFS was 13.6 months versus 5.4 months; and in a third group that included germline or somatic BRCAm plus BRCA wild-type, the median PFS was 10.8 months for patients on rucaparib versus 5.4 months for those on placebo.

Although the trials produced striking efficacy data, “it’s also important to balance [treatment decisions] with knowledge of toxicity, and, in truth, all PARP inhibitors share some common toxicities in terms of gastrointestinal toxicities, as well as hematological adverse events [AEs],” Campos said. Common AEs included anemia, neutropenia, and thrombocytopenia. “Thrombocytopenia was seen a bit frequently in the NOVA trial very early on, but it was clearly attenuated with a dose reduction, so that is quite important.

“There are other toxicities that can be unique to 1 or 2 particular agents, and as you tailor these drugs to your patients, knowing these toxicities is extremely important,” Campo continued. Metabolic effects and drug-to-drug interactions are also important to understand, she noted.

“We want these drugs in the up-front setting,” Campo said, adding that the question is whether past and ongoing trial activity will provide the necessary evidence for doing so. Other riddles need to be solved, too, such as how the mechanisms of resistance to PARP inhibitors work and whether PARP inhibitors can be used after PARP inhibitors. “The elephant in the room is, how can testing strategies for BRCAm or non-BRCAm ovarian cancer be used to personalize treatment strategies?” she said.

Nevertheless, there’s enough ongoing trial activity to guarantee that some answers will emerge. “We often think of patients we could have given these drugs to many years ago and didn’t have them to give. It’s a very exciting time in the management of ovarian cancer,” Campos concluded.
 
Breast Cancer

Dandelion Toolkit Increases Understanding in Patients With Newly Diagnosed Metastatic Disease

Meg Barbor, MPH

When patients receive a metastatic breast cancer diagnosis, they face challenging and often overwhelming hurdles to understanding their disease. They are usually handed text-heavy materials written at a high literacy level, making this crucial information inaccessible for low-literacy or high-anxiety patients. But a Metastatic Breast Cancer Communications Toolkit, affectionately referred to as the Dandelion Toolkit, could help.

Research for the toolkit was commissioned by the Metastatic Breast Cancer Alliance in response to communication gaps identified in its “Changing the Landscape for People Living with Metastatic Breast Cancer” report. The report found that patients don’t often receive adequate information from healthcare professionals enabling them to understand the disease and its treatments so they can make informed decisions. The Alliance approached Worldwide Breast Cancer to assist.

The Dandelion Project, a clinical study designed to help patients visualize cancer concepts, could improve shared decision making and foster open communication among oncologists, nurses, and navigators during those initial discussions, according to Corrine Ellsworth Beaumont, PhD, and founder of Worldwide Breast Cancer in Lewisville, Idaho, and colleagues.

“Being diagnosed with metastatic breast cancer is a life-threatening situation, and we know from talking to patients that they don’t remember much of that initial conversation at all,” she told Oncology Nursing News® at the European School of Oncology–European Society for Medical Oncology International Advanced Breast Cancer Fourth International Consensus Conference in Lisbon, Portugal. “Part of the reason for that is it’s a very abstract conversation. Physicians are talking about ER-positive and HER2-negative status, pathology reports, etc, and there’s nothing concrete to really understand. What we do is make that conversation visual and concrete.”

CURRENT LACK OF ENGAGEMENT

Patients often overestimate their knowledge of their disease, and as a result, they also overestimate their ability to participate in shared decision making, Beaumont noted. In 2015, Worldwide Breast Cancer surveyed about 500 patients with metastatic breast cancer. When asked if they knew their cancer type, 96% of respondents said yes, but when asked for specifics, only 46% could give both their HER2 and hormone receptor status; 13% gave no answer, 21% provided stage/location only, and 20% gave a partial description.

One-third of respondents reported feeling their knowledge was inadequate for participation in decision making, 71% did not recall life goals and hobbies being a part of their pretreatment discussions, only 24% got a second opinion, and 58% said they felt rushed and that starting treatment was urgent. “We’re finding that what patients think they know and what they actually know are 2 different things,” Beaumont said. Healthcare providers are faced with the difficult task of determining the difference.

Although many education campaigns have been developed, none offer a multilingual, multicultural solution to overcoming these communication hurdles, the researchers maintain. The Dandelion Toolkit helps patients visualize their cancer and its staging, as well as possible treatment courses, using—yes—a dandelion (mbcalliance.org/education-access-initiatives/dandelion).

THE VISUAL AIDS

The Dandelion Toolkit is in 2 parts: tear off sheets used by oncologists during initial diagnosis and a deck of cards designed specifically for oncology nurses to use with patients when explaining their specific treatments and routine care during treatment, such as blood tests. A normal cell is illustrated by a healthy, yellow dandelion, while stage IV breast cancer is represented by a dandelion losing its spores in the wind (eg, spreading to other parts of the body).

Chemotherapy is illustrated by a chemical being poured on the entire lawn, killing both the grass and the dandelion. A chemical that kills the dandelion but spares the grass represents targeted therapy. Hormonal therapy is illustrated by targeting the seeds of the dandelion, making it difficult to reproduce; radiation is akin to a withered spot where the dandelion is growing; and surgery is illustrated by digging the dandelion out.

Using surgery as an example, Beaumont explained the power of these visuals. “If you had a backyard full of dandelions, you wouldn’t think digging them all out means they’ll never come back again,” she said. “It’s the same thing with metastatic breast cancer. Simply removing it is not going to stop the problem, because the seeds can spread and you don’t know exactly where all those tiny seeds have gone.”

Picturing a cancer cell like a dandelion seed made up of 2 parts—proteins (HER2, CDKs) and hormones (ER, PR)—aids understanding of subtypes. “Helping patients picture subtype by using a seed, instead of relying on abstract medical acronyms, can improve understanding, which is greatly lacking,” she said. “They can use that understanding to explain their cancer to family and friends, but importantly, it means patients can start participating in decisions.”

A prototype of the Dandelion Toolkit is being tested in a clinical trial at 6 pilot sites in the United States, Mexico, Australia, and Turkey. According to Beaumont, nurses at the pilot sites have said the prototype has helped them overcome emotional barriers, especially with helping patients’ family and friends understand what is happening to their loved ones. “But it’s also allowing the healthcare team, for the first time ever, to have a consistent message with the patient,” she said.

The results will inform the development of an information toolkit for healthcare professionals to better communicate with patients who have metastatic breast cancer regarding diagnosis and treatment decisions.

 
Lymphoma

Frontline A + AVD Bests ABVD for Advanced Hodgkin Lymphoma

Katie Kosko

Patients with advanced-stage Hodgkin lymphoma (HL) saw a 23% risk reduction in progression, death, or need for additional therapy with the use of brentuximab vedotin (Adcetris) plus doxorubicin (Adriamycin), vinblastine, and dacarbazine (A + AVD) as frontline therapy, according to investigators who presented their findings at the 2017 American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta.

The results of the phase III ECHELON-1 study, which compared A + AVD with standard chemotherapy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), also were published online in the New England Journal of Medicine.

“The study results represent the first successful effort in more than 30 years to improve outcomes of first-line treatment in patients with advanced HL without escalating the toxicity of the chemotherapy to unacceptable levels,” said Joseph M. Connors, MD, clinical director of the British Columbia Cancer Agency Centre for Lymphoid Cancer in Vancouver, Canada, and lead author on the study.

The study, conducted at 218 sites in 21 countries, enrolled 1334 patients with stage III or IV HL who had no prior therapy and an ECOG performance score of 2 or less. Patients ranged in age from 18 to 83 years (median age: 36), and 58% were men.

Patients were randomly assigned 1:1 to receive A + AVD (brentuximab vedotin 1.2 mg/kg, doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) or ABVD (doxorubicin 25 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) intravenously on days 1 and 15 of up to 6 cycles of 28 days. Patients were followed up on every 3 months for 36 months, then every 6 months until the close of the study.

At the end of chemotherapy, patients were reassessed using CT and PET scanning and then followed to determine the success of the treatment.

The primary endpoint was modified progression-free survival (PFS), defined as time to progression, death, or evidence of incomplete response, followed by subsequent anticancer therapy and determined by an independent review facility assessment.

PFS was met with 117 events in the A + AVD arm and 146 events in the AVBD arm. Modified PFS events were attributed to disease progression (90 vs 102), death (18 vs 22), or receipt of additional anticancer therapy for incomplete response (chemotherapy: 7 vs 15; radiotherapy: 2 vs 7). At a median follow-up of 24.9 months, the 2-year modified PFS was 82.1% (95% CI, 78.7%-85.0%) with A + AVD compared with 77.2% (95% CI, 73.7%-80.4%) with ABVD.

“The difference in the 2 outcomes at the 2-year mark is just shy of 5% and documents that about a quarter of patients that otherwise would have had a failure of their primary therapy were successfully treated with the new combination, further reducing the likelihood that patients would experience eventual progression of treatment refractory disease,” Connors said.

In addition, researchers found that 33% fewer patients treated with the A + AVD regimen received subsequent chemotherapy or high-dose chemotherapy and transplant compared with those treated with ABVD.

Safety profiles were consistent with known toxicities of the single agents, according to Connors. Grade ≥3 infections were more common in the A + AVD arm (18%) than the ABVD arm (10%).

Neutropenia was reported in 58% of patients who received A + AVD compared with 45% who received ABVD. In the A + AVD arm, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) than among those who did not (11% vs 21%).

Peripheral neuropathy occurred in 67% of patients receiving A + AVD and 43% receiving ABVD. With appropriate reduction in dose or change in scheduling, the majority of patients recover from the peripheral neuropathy, Connors said. Researchers also found that interstitial lung disease occurred more frequently and severely in patients receiving AVBD (grade ≥3, 3% ABVD vs <1% A + AVD).

There were 28 deaths in the A + AVD arm and 39 in the ABVD arm (HR for interim overall survival, 0.72; 95% CI, 0.44-1.17%; P = .19). Among the deaths that occurred during treatment, 7 of 9 in the A + AVD group were associated with neutropenia, and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.

REFERENCE

Connors J, Jurczak W, Straus D J., et al. Brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine (A+AVD) as frontline therapy demonstrates superior modified progression-free survival versus ABVD in patients with previously untreated stage III or IV Hodgkin lymphoma (HL): the phase 3 echelon-1 study. Abstract presented at: 2017 ASH Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA. Abstract 6. .
 

Nurse Perspective

Melissa Baker, RN, MSN, OCN, APN-CMelissa Baker, RN, MSN, OCN, APN-C
Adult Blood & Marrow Stem Cell Transplantation Program, John Theurer Cancer Center, Hackensack, NJ


Findings from the large, open-label, phase III ECHELON-1 study demonstrated that brentuximab vedotin (Adcetris) plus doxorubicin (Adriamycin), vinblastine, and dacarbazine (AVD) is a highly effective regimen with a superior modified progression-free survival (PFS) in patients who have advanced Hodgkin lymphoma (HL).

In the A + AVD arm, 33% fewer patients received subsequent salvage chemotherapy compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), the standard frontline regimen in patients with advanced HL—a finding that poses a significant change.

While effective, the use of bleomycin in the ABVD regimen increases the risk of pulmonary toxicity that affects quality of life and can be fatal. Data from the ECHELON-1 study showed that A + AVD is more effective than ABVD for treating patients with advanced HL, with nearly a 6.5% lower risk of progression (82% in A + AVD vs 77% in ABVD). Removing bleomycin decreased the risk of lung toxicity, which was reported in 2% of patients in the A + AVD arm versus 7% receiving ABVD. However, the benefit came at the price of different toxicities—namely, peripheral neuropathy and neutropenia. Neutropenia was remedied with prophylaxis use of growth factor agents.

Although this finding demonstrates a statistically significant improvement in modified PFS, it is unclear if a 6.5% difference justifies the higher cost associated with the targeted antibody therapy. Adding prophylactic growth factor agents would certainly drive up treatment costs. A cost-effective comparative analysis between the 2 regimens is warranted.

Another concern: Using brentuximab vedotin as a frontline agent could impact the role of brentuximab vedotin in salvage therapy or as a bridge to transplant, as some speculate.

Results from this trial change the management of advanced HL and pose a potential new frontline therapy. However, the justification of the increased financial burden associated with brentuximab vedotin and the use of frontline brentuximab vedotin on the ability to employ this agent in the salvage setting is still under investigation.
 

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