Clinical Insights: October 2018

Tuesday, October 23, 2018

Release Date: October 22, 2018
Expiration Date: October 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 patients with cancer
ACCREDITATION/CREDIT DESIGNATION STATEMENT

Physicians’ Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 1 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/ONN18October
  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®.

Breast Cancer

Magnetic Localization System for Lymph Node Biopsy in Breast Cancer

Jason Harris

The Magtrace and Sentimag Magnetic Localization System is the first nonradioactive system approved by the Food and Drug Administration (FDA) for identifying and removing sentinel lymph nodes in women undergoing mastectomy for breast cancer. Magnetic Magtrace particles are injected into the patient’s breast tissue and become trapped in the lymph nodes. The surgeon then applies the Sentimag probe to the patients’ skin near the tumor site and detects the magnetic particles located within the sentinel lymph node, the one closest to the tumor. That node is then removed and tested for the presence of cancer cells. The system’s manufacturer, Endomag, says the device is less invasive than wire-guided localization and allows greater flexibility in scheduling for patients, surgeons, and radiologists. And, it does not require the injection of radioactive materials.

The SentimagIC trial (NCT02336737), a pivotal, prospective, open-label, multicenter, paired comparison study, evaluated Magtrace versus a Technetium 99–labeled sulfur colloid radioisotope/isosulfan blue dye control. The primary endpoint was noninferiority for lymph node detection rate.

A total of 160 women with clinically node-negative early-stage breast cancer enrolled at 6 sites in the United States from January 2015 to December 2015. The intent-to-treat cohort included 147 patients. The majority of patients (37.8%) had stage II disease, 33.3% had stage I disease, and 27.4% had stage III disease. There were no patients with stage IV disease. The mean age was 61.1 years, and 82.3% of the cohort was white. Nineteen percent of patients were premenopausal, 3.4% were perimenopausal, and 77.6% were postmenopausal.

In total, 348 lymph nodes were detected by Magtrace compared with 345 for the control. The per node detection rate was 93.5% (95% CI, 91%-96%) for the control versus 94.3% (95% CI, 91.9%-96.7%) for Magtrace, a difference of 0.8% (95% 1-sided lower confidence bound, –2.1%). The per patient detection rate was 98.6% (95% CI, 95.2%-99.8%) with Magtrace and 98% (95% CI, 94.2%-99.6%) for the control.

The overall per patient concordance rate was 98% (95% CI, 94.2%-99.6%). In patients with at least 1 metastatic node (n = 22), the detection rate was 95.5% (95% CI, 86.8%- 100%) for both modalities.

Magtrace detected 22 nodes missed by control, while the control detected 19 nodes missed by Magtrace. However, investigators found that both modalities detected all malignant nodes and all discordant nodes were benign. Investigators recorded 69 adverse events (AEs) in 56 of 147 (38.1%) patients. Nine (13%) of those AEs were considered serious, but investigators determined that 7 of those were not related to Magtrace. The cause of the other 2 serious AEs was undetermined. Breast discoloration/hyperpigmentation (16.3%) and ecchymosis/bruising (6.8%) were the most common AEs. Patients who had mastectomy (29.3%) did not display discoloration at follow-up visits 6 to 22 days after surgery.

The FDA recommends against using the system in patients with a metal implant in the axilla or in the chest or who have iron overload disease. Sentimag is not indicated for patients with hypersensitivity to dextran compounds or iron oxide. The use of a nonradioactive process for lymph node detection and removal would benefit hospital staff in addition to the patients. According to a statement on the Endomag website, “The Sentimag platform can help hospitals to reduce their reliance on radioactive tracers, [and] reduce the exposure of their staff and patients to radioactivity.” 

REFERENCE
FDA. Summary of safety and effectiveness data (SSED). FDA website. accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P160053. Published July 24, 2018. Accessed July 25, 2018.
 
Brain Cancer

Poliovirus Genetically Altered to Target Brain Tumors Shows Early Signs of Success

Katie Kosko

Researchers from Duke Cancer Institute in Durham, North Carolina, may have found an unlikely treatment for glioblastoma multiforme (GBM): the poliovirus.

In a phase I clinical trial, researchers genetically modified the poliovirus. Then they injected it into tumors. Promising results, published in the New England Journal of Medicine, showed a 3-year survival rate of 21% compared with just 4% in a historical control group of patients who received standard therapy.

“Patients with glioblastoma have failed to respond to immunotherapy drugs available for other cancer types, [so] it is exciting to know that the genetically modified poliovirus was able to trigger an immune reaction in [these] patients,” Annick Desjardins, MD, FRCPC, director of clinical research at The Preston Robert Tisch Brain Tumor Center at Duke, said in an interview with CURE®, a sister publication to Oncology Nursing News®. “The survival observed is similar to other tumors treated with immunotherapy, but quite exciting for recurrent patients with glioblastoma, given their known poor survival.”

The trial, which launched in 2012, was made up of 61 patients who were enrolled based on the size of their recurring tumor and its location in the brain. The median overall survival (OS) was 12.5 months compared with 11.3 months for the historical control group. At 2 years, patients treated with the poliovirus had an OS of 21%, whereas the historical control group only saw an OS of 14%.

Investigators planned to increase the dosage in all patients; however, the 15 patients who received higher doses experienced too much inflammation that resulted in adverse events (AEs) like seizures and cognitive disturbances. Sixty-nine percent of patients had a mild or moderate AE occur.

“The activation of the immune response triggers a localized inflammation, or immune reaction,” Desjardins said. “The side effects were in relation to the brain function in proximity to the tumor injected with the genetically modified poliovirus. For example, if the lesion was close to the speech center, the side effect would be word-finding difficulties.”

GBM is the fastest growing type of brain cancer and accounts for more than half of all gliomas, according to the American Cancer Society. Men are more prone to developing GBM than women.

Typically, GBM is treated by removing as much of the tumor as possible with surgery. Radiation and chemotherapy can be used afterward to help kill any remaining tumor cells or as main treatment if the tumor cannot be removed surgically. Once GBM recurs, the survival rate is often limited to less than 1 year.

Brain cancers are difficult to treat because of the blood-brain barrier, which helps prevent harmful toxins and bacteria from entering; however, this also means anticancer drugs may be blocked, too. The poliovirus is ideal in treating recurrent GBM for several reasons, explained Desjardins.

“The poliovirus receptor is present on all solid tumors, which means that all solid tumors will get infected by the genetically modified poliovirus if put in contact with it,” she said. “Another positive is that the poliovirus survives for only a short period of time: It triggers the infection and the immune activation but then disappears. It does not stay around and decrease the long-term immune response like other viruses might do.”

In May 2016, the Food and Drug Administration granted a breakthrough therapy designation to the genetically modified poliovirus, PVSRIPO, which will hopefully help expedite research into this line of therapy.

For this study, the phase II trial is ongoing in adults with recurrent GBM, and a phase II trial is open for pediatric patients with a recurrent brain tumor. Investigators plan to soon begin trials in patients with melanoma and breast cancer.

“It is hard work to retrain the part of the brain affected by the inflammation, and not all patients can safely receive the treatment given the location of their tumor,” Desjardins said.

“However, for the patients who can safely receive the drug, a group will see their disease controlled for a long period of time,” she added. “This is just the beginning of our understanding on how to activate the immune system for patients with brain tumors.”
 
Gastric Cancer

TAS-102 Prolongs Survival in Patients With Advanced Gastric Cancer

Staff

Patients with heavily pretreated metastatic or advanced gastric cancer who received TAS-102 (trifluridine/ tipiracil; Lonsurf) saw a significant overall survival (OS) benefit, according to phase III study findings presented at the 2018 World Gastrointestinal Cancer Congress.

Investigators of the TAGS study revealed that the oral anticancer agent reduced the risk of death in patients by 31% compared with placebo. The median OS was 5.7 months with TAS-102 compared with 3.6 months for placebo (HR, 0.69; 95% CI, 0.56-0.85; P = .0003). At 12 months, the OS rates were 21.2% and 13%, respectively, representing a significant improvement in survival for those with a poor prognosis.

“TAS-102 represents an effective treatment option for patients with heavily pretreated metastatic gastric cancer,” said lead investigator Josep Tabernero, MD, PhD, director of the Val de Hebron Institute of Oncology in Barcelona, Spain. “Most patients with gastric cancer present with advanced or metastatic disease and, therefore, have a poor prognosis. The 5-year overall survival rate is just 4%.”

TRIAL DESIGN

The TAGS study investigated the efficacy and safety of TAS-102 plus best supportive care (BSC) compared with placebo plus BSC in patients with metastatic gastric cancer that was refractory to standard treatments. Patients were randomized in a 2:1 ratio to receive TAS-102 at 35 mg/m2 twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle (n = 337) or placebo (n = 170). Poststudy systemic therapy was received by a quarter of patients in each group.

Patient characteristics were similar in the treatment arms. The primary cancer site was gastric in 71% of patients in both arms, and 44% per arm had received prior gastrectomy. Approximately 37% of patients in each group had received 2 prior treatments, and about 63% had received 3 or more prior treatments, including fluoropyrimidine, platinum, irinotecan, taxanes, ramucirumab, and immunotherapy. Twenty percent and 16% of patients in the TAS-102 and placebo arms had HER2-positive tumors, with 18% and 14% of patients, respec-tively, receiving prior anti-HER2 therapy.

The ECOG performance status was 1 for 64% and 60% of patients and the median ages were 64 and 62.5 years in the TAS-102 and placebo groups, respectively. Overall, approximately 15% of patients were enrolled in Japan and the rest were from other parts of the world.

The primary endpoint of the TAGS study was OS, and the secondary endpoints focused on progression-free survival (PFS) and quality of life (QoL). Computed tomography scans were performed every 8 weeks and QoL assessments every 4 weeks. Crossover to open-label TAS-102 was allowed.

The median PFS with TAS-102 was 2 versus 1.8 months with placebo, representing a 43% reduction in the risk of progression or death (HR, 0.57; 95% CI, 0.47-0.70; P <.0001). The 6-month PFS rates were 21% and 13%, respectively.

As of the March 31, 2018, data cut-off, 19 patients (6%) in the TAS-102 cohort and 3 (2%) in the placebo group remained on treatment. Discontinuation was due to disease progression in 76% and 87%, respectively. Ten percent of patients in the TAS-102 arm discontinued due to an adverse event (AE) compared with 7% in the placebo group.

AEs

Treatment-related AEs occurred in 81% and 57% of patients in the TAS-102 and placebo groups, respectively, and the corresponding deaths rates were low at 0.3% and 0.6%. The most common nonhematologic grade ≥3 AEs for TAS-102 and placebo, respectively, were decreased appetite (9% vs 7%), fatigue (7% vs 6%), general physical deterioration (7% vs 9%), asthenia (5% vs 7%), vomiting (4% vs 2%), abdominal pain (4% vs 9%), nausea (3% vs 3%), and diarrhea (3% vs 2%).

The most common grade 3/4 hematologic laboratory abnormalities in the TAS-102 group versus placebo, respectively, were neutropenia (38% vs 0%), leukopenia (21% vs 0%), lymphocytopenia (19% vs 8%), anemia (19% vs 7%), and thrombocytopenia (6% vs 0%). Two percent of TAS-102– treated patients had febrile neutropenia.

“TAS-102 showed a predictable and manageable safety profile, consistent with that seen previously in patients with metastatic gastric cancer,” Tabernero said.

In addition to gastric cancer, TAS-102 has been investigated as a treatment for colorectal cancer. The agent was approved by the Food and Drug Administration in 2015 as a treatment for patients with colorectal cancer who were previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based che-motherapy; an anti-VEGF biological therapy; and, if RAS wild-type, an anti-EGFR therapy.

Taiho intends to submit a supplemental new drug application to the FDA for TAS-102 consideration as a third-line treatment option for appropriate patients with metastatic gastric cancer.

REFERENCE
Tabernero J, Shitara K, Dvorkin M, et al. Overall survival results from a phase III trial of Trifluridine/Tipracil vs placebo in patients with metastatic gastric cancer refractory to standard therapies (TAGS). Ann Oncol. 2018;29(suppl 5; abstr LBA-002). academic.oup.com/annonc/article/29/ suppl_5/mdy208.001/5043314.
 
Ovarian Cancer

Niraparib Shows Durable Responses in Recurrent Ovarian Cancer Regardless of BRCA Mutation

Kristie L. Kahl
 
ARP inhibitors are currently approved by the Food and Drug Administration (FDA) to treat women with ovarian cancer and breast cancer who have BRCA mutations. The results of a recent study presented at the 2018 American Society of Clinical Oncology Annual Meeting showed that one PARP inhibitor could have wider applications. Findings from the QUADRA study showed that treatment with niraparib (Zejula) led to durable responses beyond those seen in patients with BRCA-positive late-line ovarian cancer.

UNMET NEEDS IN OVARIAN CANCER

Ovarian cancer is a disease that is often diagnosed at late stages, with a high possibility of recurrence. There is an unmet medical need for better treament solutions for this patient population.

“Chemotherapy and surgery work pretty well in the first-line setting, but the problem is that 85% of women will have their cancer recur. And once it has recurred once, it is going to keep recurring,” Martin Huber, MD, senior vice president and chief medical officer at TESARO, said in an interview with CURE®, a sister publication to Oncology Nursing News®.

“The real unmet medical need is that each time you treat them, the interval that the chemotherapy works for gets shorter and shorter,” he added. “What ends up happening [is that] women use 3 or 4 lines of chemotherapy treatment, and they are basically running out of options.”

In the maintenance setting of women with platinum-responsive relapsed ovarian cancer, niraparib demonstrated improved progression-free survival (PFS) rates compared with placebo. In particular, the agent was effective regardless of BRCA mutation homologous recombination deficiency (HRD) status.

STUDY DESIGN

In the open-label, single arm, phase II QUADRA trial, researchers evaluated the safety and efficacy of niraparib at 300 mg once daily as a fourth-line or greater treatment in 463 patients with ovarian cancer, regardless of platinum or biomarker status.

Objective response rate (ORR) served as the primary endpoint of the study, while secondary endpoints included durability of response, disease control rate, PFS, overall survival (OS), safety, and tolerability. The primary efficacy population included fourth- or fifth-line patients who were previous PARP-inhibitor naïve, platinum sensitive, and HRD positive (n = 45).

Of note, less than 20% of patients had a BRCA mutation, 27% received niraparib as a sixth- or later line therapy, two-thirds were platinum resistant or refractory (33% and 35%, respectively), and 48% were HRD positive. In addition, the majority of platinum-sensitive patients were considered platinum ineligible and 62% had received prior treatment with bevacizumab (Avastin).

Of the 45 patients in the primary efficacy population, ORR was 29%. Those who were fourth- or later line treated, HRD positive, and platinum sensitive (n = 51) experienced an ORR of 27%, which included a disease control rate of 69% and a duration of response of 9.2 months. In patients treated with niraparib as a fourth-line therapy or later, patients with a BRCA mutation and those who were HRD positive and platinum sensitive had clinical benefit rates of 53% and 49%, respectively, for at least 16 weeks. Across the entire patient population, the median duration of response was 9.4 months, with an estimated 44% of all responses lasting 12 months or more.

The median OS in all patients treated with niraparib as a fourth line therapy or later was 17.2 months; in HRD-negative or unknown patients, 16.6 months; in HRD-positive patients, 19 months; and in patients with BRCA mutations, 26 months.

The most common grade 3/4 adverse events (AEs) included anemia (26.3%) and thrombocytopenia (20.5%), which were generally managed with dose modifications.

Huber noted TESARO plans to use these results to submit a supplemental new drug application to the FDA by the end of this year. “What is important is that [the] response rate is similar to what we have seen in the BRCA population. So, what we were very excited by is that we saw efficacy beyond the BRCA population,” said Huber. “That is leading us to now look at our opportunities for doing a regulatory file and making this available to not only treatment for women with a BRCA mutation, but women who have ovarian cancer beyond the BRCA mutation.”

Nurse Perspective

Carol Rios, MSN, RN, APN, NP-C, OCN, CBCN Carol Rios, MSN, RN, APN, NP-C, OCN, CBCN
Breast and Women’s Health Oncology Division
John Theurer Cancer Center
Hackensack, NJ


Targeted therapy has changed cancer treatment. With the evolution of PARP inhibitors, great advances have been made in women’s cancer.

Initially approved by the Food and Drug Administration on March 27, 2017, niraparib (Zejula) is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. PARP inhibitors are usually more effective in patients with somatic or germline BRCA mutations. Germline mutations can be inherited, and all cells in the body are affected. Somatic mutations affect only cells that originate from the mutated cell; for instance, the cancer cell that replicates. There are various options for somatic mutations that test the cancer tumor and/or blood. The QUADRA study’s positive outcomes in both BRCA-positive and BRCA-negative populations present another treatment option for oncologists to offer women who have recurrent ovarian cancer.

In ovarian cancer, the recurrence rate is high, especially after an initial recurrence. Niraparib and other PARP inhibitors bring hope to these women. These medications have less toxicity than chemotherapy, so patients can experience a better quality of life when using them.

Niraparib is generally well tolerated. Thrombo-cytopenia can happen quickly in some patients, however, so it is vital for nurses to closely monitor platelet counts. Lab tests should include weekly complete blood counts, initially.

I have observed that patient adherence can be a barrier to care among patients taking niraparib. Contributing factors are financial hardship due to high copays and cumulative toxicities in patients who have been heavily pretreated. However, the future of PARP inhibitors in ovarian cancer treatment is bright, and the uses in the adjuvant setting and in combination with other cancer-fighting therapies deserve further exploration.
 
Lymphoma

Survival Time Doubles in Mantle Cell Lymphoma With the Advent of Targeted, Combination Therapies

Jessica Skarzynski

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma with a generally poor prognosis. Now there is good news for these patients: Survival rates have nearly doubled thanks to improvements in the treatment landscape over the past 10 years, according to study results published in the British Journal of Haematology.

Clinical findings in recent years indicate survival rate improvements in this patient population. To determine if the effects observed in clinical trials have translated to the real world, researchers examined data from 335 UK-based patients who received a diagnosis of MCL between 2004 and 2015. Encouragingly, they found that as treatment evolved to include combination therapies and the biology of the disease became better understood, survival rates improved for patients across the disease spectrum.

“Although MCL continues to have a poor prognosis and remains one of the most challenging lymphomas to treat, our analyses confirm that marked therapeutic changes introduced in recent years appear to be having a favorable impact on outcome in the general patient population,” the investigators wrote.

Initially, first-line rituximab (Rituxan) marked the first notable improvement in treatment: Survival times for patients newly diagnosed increased from 2 years to 3.5 years. This improvement was also seen when rituximab was added to chemotherapy. “Our data clearly demonstrate the benefit of the addition of rituximab to first-line chemotherapy in the general patient population; at 3.1 years, the median survival of those who received rituximab immunochemotherapy at first line was twice that of those who did not,” the investigators wrote.

Additionally, survival times among those who relapsed between 2004 and 2011 improved from 8 months to nearly 17 months in those who relapsed at some point between 2012 and 2015. The investigators credited this improvement to new treatments such as bendamustine, which was introduced in 2012, and the targeted therapy ibrutinib (Imbruvica), which blocks signals that stimulate the growth and division of malignant cells.

“Encouragingly, our population-based findings confirm that these novel agents seem to be impacting particularly on the survival of patients who may be less able to withstand intensive treatment,” the investigators wrote. “The 1-year overall survival among patients over 70 years treated for relapsed/refectory disease almost [doubled], reaching 50% and matching that of patients under 70 years of age.”

The investigators noted that their analysis highlights the importance of monitoring the impact of treatment changes on the patient population in real time and that they hope to assess the impact of other novel agents, such as lenalidomide (Revlimid), on treatment.

“Our findings show an improvement in survival across a population with a disease that is challenging to treat,” they added.

Nurse Perspective

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


Although mantle cell lymphoma (MCL) is rarely a curable disease outside of stem cell transplant, it is encouraging that survival rates have nearly doubled with the advent of targeted combination therapies.

Oncology nurses play a pivotal role in optimizing patient care through assessment, education, symptom management, and sup-portive care. Anticipating and managing common adverse events (AEs), such as infusion-related reactions during rituximab or the risk of tumor lysis in patients with high tumor burden, is a critical component of patient care.

While patients need advanced nursing assessment to prevent complications during an infusion, they also need teaching to manage possible AEs in the home setting. Teaching patients that ibrutinib capsules should not be opened, broken, or chewed and should be taken with a glass of water at the same time each day is essential to optimize patient care. Educating patients on the management of diarrhea that may occur with ibrutinib or AEs associated with immune-modulatory drugs, like lenalidomide, or with other biologically targeted therapies is necessary.

Sophisticated treatments challenge oncology nurses to be independent critical thinkers and to analyze, reflect, and apply high-level knowledge to their patients. Extending survival leads to new challenges, and patients are treated similar to the way patients with chronic conditions are treated. For example, they may need long-term medication use and should be monitored for adherence. Nurses should manage AEs early and assess for drug interactions (especially in the elderly). Family planning, psychosocial, and financial issues all should be addressed. Using a collaborative approach, the oncology nurse plays a vital role in caring for these complex patients with MCL.


External Resources

MJH Associates
American Journal of Managed Care
Cure
MD Magazine
Pharmacy Times
Physicians' Education Resource
Specialty Pharmacy Times
TargetedOnc
OncNurse Resources

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