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Clinical Insights: June/July 2019

Monday, July 22, 2019

Release Date: July 22, 2019
Expiration Date: July 22, 2020


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/ONN19JULY
  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®.

Melanoma
Jessica Skarzynski

Diet May Affect Response to Immunotherapy in Patients With Melanoma


Patients with melanoma who eat a fiber-rich diet could see an improved response to treatment with immunotherapy, according to research presented at the American Association for Cancer Research Annual Meeting 2019.1

During a webcast preview of the event, Christine Spencer, PhD, a research scientist at the Parker Institute for Cancer Immunotherapy, based in San Francisco, California, discussed preliminary data on her research with colleagues at The University of Texas MD Anderson Cancer Center (MD Anderson). The team investigated the correlation between gut microbiome features and immuno- therapy responses in patients with cancer.

Just 20% to 30% of patients respond to checkpoint blockade immunotherapy, although responses could be enhanced if patients consume high-fiber foods, which give rise to diverse microbiome in the gut, Spencer said.

According to previous research by Spencer and her colleagues, the gut microbiome, which encom- passes communities of microbes within the human gut, plays an important role in immune system regulation.

“What we found in profiling patients prior to therapy was that certain features of the gut microbiome were associated with response,” Spencer said. Better response to checkpoint inhibitors was associated with “higher micro- biome diversity, which is a greater richness in terms of the types of bacteria present in the gut,” she said.

In particular, researchers found that patients with melanoma who had a diverse gut microbiome rich with bacteria from the Ruminococcaceae family responded favorably to anti–PD-1 therapy, whereas patients with less bacterial diversity had a poor response to this treatment.

Spencer et al set out to discover why some patients had a favorable response related to their gut microbiome. Specifically, they wanted to know if diet had an impact on the gut microbiome that also correlated with response to immunotherapy.

The investigators collected surveys on diet and supplement use from 113 patients with melanoma undergoing treatment at MD Anderson. They also profiled the diversity and type of bacterial species found in the microbiome of these patients by analyzing fecal samples prior to therapy.

Preliminary data show that patients who reported eating high-fiber diets, including fruits, vegetables, and whole grains, were about 5 times as likely to respond to anti–PD-1 immuno- therapy, Spencer said.

Over 40% of patients reported taking probi- otics before starting therapy, but results also showed that taking these supplements was associated with lower gut microbiome diversity. Low gut-microbiome diversity has been linked to poorer response to checkpoint inhibitor immu- notherapy, Spencer noted. “There’s a perception that taking probiotics improves gut health, but our results, although early, suggest that may not be the case for patients with cancer,” she said.

Different foods and supplements may affect a patient’s response to immunotherapy, Spencer said: “We think this is likely mediated by the gut microbiome.”

Patients should be encouraged to eat high- fiber foods, according to Spencer. Although many are already aware of the health bene- fits previously associated with this type of diet, she said, they should be informed about these findings that link fiber to a more diverse gut microbiome and a better response to cancer immunotherapy.

In addition, she said, patients interested in taking over-the-counter probiotic supplements should discuss the risks and benefits with their doctors. “A lot of people have the perception that probiotics will provide health benefits, but that might not be the case in cancer patients,” Spencer said. “We’re not saying that all of them are bad, but the message is that these factors have never before been studied in patients on immunotherapy, and our data suggest for the first time that they could matter.”

Next, Spencer and her team plan to validate their research results in larger cohorts, a project they have already begun.



REFERENCE
Spencer CN, Gopalakrishnan V, McQuade J, et al. The gut microbiome of melanoma patients is distinct from healthy controls, and associations with treatment outcomes are influenced by host lifestyle factors. Presented at: American Association for Cancer Research Annual Meeting 2019 media preview; February 27, 2019; Philadelphia, PA.  
Breast Cancer
Gina Columbus

Surgery Is Linked to Improved OS in Stage IV, HER2+ Breast Cancer


Primary tumor surgery for patients with stage IV, HER2-positive breast cancer is associated with an improvement in overall survival (OS), according to results of a retrospective cohort review presented at the American Association for Cancer Research Annual Meeting 2019.1

At a median follow-up of 21.2 months (range, 0-52), the median OS for patients who had surgery was 25 months compared to 18 months in those who did not, leading to a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.40-0.77; P = .0004).

Prior data evaluating the survival benefit of primary breast cancer surgery have been mixed, with 1 phase III trial demonstrating no benefit2 and another, the MF07-01 study,3 that showed that with longer follow-up, there was an improve- ment in median survival with primary stage IV breast tumor resection.

With the advent of systemic therapies that have improved outcomes, surgery’s impact in this era of targeted treatments needs to be evaluated.

In the retrospective cohort review, investigators analyzed data from breast cancers in the National Cancer Database between January 1, 2010, and December 31, 2012. After investigators narrowed down for female sex, adenocarcinoma histology, invasive disease, HER2 positivity, American Joint Committee on Cancer stage IV disease, and a breast cancer diagnosis between 2010 and 2012, among other factors, the final cohort numbered 3231 patients. The primary endpoints were receipt of surgery and OS.

The variables analyzed included age, race/ ethnicity, insurance status, Charlson-Deyo score, treatment facility type, annual income, clinical tumor stage, clinical nodal stage, estrogen receptor (ER) status, progesterone receptor (PR) status, number of regional lymph nodes exam- ined, radiation therapy, chemotherapy/immu- notherapy (which was used as a surrogate for HER2-targeted therapy), endocrine therapy, site of metastasis, and vital status.

In the overall population, 71.3% of patients were white. More patients had private insur- ance (45.9%) compared with Medicare or other government insurance (31.7%). A total of 34.1% of patients were treated in an academic or research facility. Regarding income, 30.2% were of the highest quartile and 19.2% were of the lowest. Seventy-five percent of patients had visceral metastases. Regarding treatment, 31.8% had radiation, 89.4% had chemotherapy/immu- notherapy, 37.7% had endocrine therapy, and 35% of patients underwent surgery.

Factors attributed to increased likelihood of surgery included having private insurance (42.3%; odds ratio, 1.93; 95% CI, 1.53-2.42) or Medicare/other government coverage (30.5%; OR, 1.36; 95% CI, 1.03-1.81). Patients with low income were more likely to have surgery (34.6%) than those with high income (34.4%; OR, 1.45; 95% CI, 1.12-1.87).

Those who underwent radiation therapy were also more likely to have surgery (47.4%) than those who did not (28.8%; OR, 2.10; 95% CI, 1.76-2.51) as well as those who also received chemotherapy/immunotherapy versus not, at 36.5% and 22.2% (OR, 1.99; 95% CI, 1.47-2.70), respectively. Patients who received endocrine therapy were also more likely to undergo surgery (41.3%) compared with those who did not receive the treatment (31.3%; OR, 1.73; 95% CI, 1.40-2.14).

Various factors affected the likelihood that patients with stage IV, HER2-positive breast cancer would undergo surgery. Those aged 20 to 39 years had a 44.5% likelihood of having surgery compared with 36.9% for those aged 40 to 59 years (OR, 0.75; 95% CI, 0.56-1.00) and 30.9% for those aged ≥60 years (OR, 0.58; 95% CI, 0.42-0.81). African American patients were less likely to have surgery (27.7%) compared with white patients (36.9%; OR, 0.68; 95% CI, 0.53-0.87), as were patients who were treated at an academic center (29.1%) versus a community practice (37.1%; OR, 0.67; 95% CI, 0.50-0.89).

Those with T4 tumors were less likely to undergo surgery (29.9%; OR, 0.67; 95% CI, 0.51- 0.80) versus patients with T3 tumors (31.8%; OR, 0.73; 95% CI, 0.53-0.99) and T0 to T2 disease (40.2%). For clinical nodal stage, those with N1 disease were least likely to undergo surgery (32.0%; OR, 0.60; 95% CI, 0.48-0.74) compared with those with N3 (33.8%; OR, 0.67; 95% CI, 0.50-0.89), N2 (34.7%; OR, 0.72; 95% CI, 0.54-0.95), and N0 disease (42.3%).

Factors that found not to be associated with likelihood of surgery were Hispanic ethnicity, comorbidities, and site of metastasis. Features that were not linked with survival were comor- bidities, treatment facility, ER or PR status, and clinical tumor or nodal stage.

However, there were variables linked with decreased survival: being African American (HR, 1.39; P = .002) or in the lowest income quartile (HR, 1.36; P = .01), having visceral metastases (HR, 1.44; P = .0003), or undergoing radiation therapy (HR, 1.33; P = .0009). Other factors were associated with an increase in survival compared to the rest of the study population: being 40 to 59 years of age (HR, 0.04; P <.0001), having Medicare or other government insurance (HR, 0.36; P <.0001), and receiving chemo- therapy/immunotherapy (HR, 0.76; P = .008) or endocrine therapy (HR, 0.70; P = .0006).

Study limitations included the fact that it was retrospective, targeted therapy was not specified, there was limited comorbidity assessment, and selection bias existed.

REFERENCES 1. Mudgway R, Chavez de Paz Villaneva C, Lin AC, et al. The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy. Presented at: 2019 American Association for Cancer Research Annual Meeting; March 29-April 3, 2019; Atlanta, GA. Abstract 4873.

2. Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 2015;16(13):1380-1388. doi: 10.1016/S1470-2045(15)00135-7.

3. Soran A, Ozmen V, Ozbas S, et al. Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: protocol MF07-01. Ann Surg Oncol. 2018;25(11):3141-3149. doi: 10.1245/s10434-018-6494-6.
Lung Cancer

Study Results Validate Speed, Accuracy of Liquid Biopsies Identifying NSCLC Biomarkers

Kristie L. Kahl

Aliquid biopsy test detected all of the guideline-recommended biomarkers in patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC) at a similar rate of detection, but with a faster turnaround time than that of tissue genotyping, according to data from the Noninvasive versus Invasive Lung Evaluation (NILE) study.

At least 1 guideline-recommended biomarker was identified by Guardant360—a 73-gene next-generation sequencing panel—in 77 patients compared within 60 patients using tissue-based tests alone (27.3% vs 21.3%; P <.0001). This included 29 patients, including 7 with negative tissue results, 16 whose tissue was not tested, and 6 who did not have enough material for the tissue-based tests. Moreover, the use of cell-free DNA (cfDNA) increased the rate of biomarker detection by 48% (from 60 to 89 patients), according to study results that were presented during a media preview of the 2019 American Association for Cancer Research (AACR) Annual Meeting.1

“Liquid biopsies can identify these muta- tions in a safe way with quick turnaround for treatment selection,” said study investigator Vassiliki Papadimitrakopoulou, MD, professor of medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center in Houston, in an interview with OncLive® ahead of the presscast. Of the 193 patients with no guideline-recommended biomarkers by tissue or liquid biopsy, 24 (12.4%) had an activating KRAS alteration identified in tissue alone (n = 3) or concordant with cfDNA (n = 21). The use of cfDNA increased the number of KRAS-positive patients from 24 to 92 by identifying an additional 68 patients with activating KRAS alterations (including 3 with negative tissue biopsies, 60 whose tissue was not assessed, and 5 who did not have enough tissue material to test).

“The downside of obtaining mutations from tissue biopsies is that usually if this testing is not done with a very powerful and comprehensive assay, such as next-generation sequencing, it is done in successive steps: one test after another, which frequently leads to depletion of the tissue sample,” Papadimitrakopoulou explained. “Therefore, you end up with testing that is not complete because the tissue is not enough for testing of all the biomarkers.”

Additionally, the investigators compared the cfDNA and tissue-based results for EGFR, ALK, ROS1, and BRAF mutations, for which there are agents already approved to treat this patient population. The results were concordant, with a positive predictive value of 100%.

Time from test order to final results was a median 9 days with Guardant360 compared with 15 days with tissue-based testing. The signifi- cantly (P <.0001) quicker results with cfDNA testing could make it more attractive to both patients and their healthcare providers.

The investigators acknowledged that the study was limited by its comparison of liquid biopsy testing to a current standard-of-care tissue genotyping test and not a tissue-based next-gen- eration sequencing test, adding that “the study results are only applicable to the Guardant360 test and not other liquid biopsy tests,” according to an AACR press release.

The prospective, multicenter study evalu- ated whether Guardant360 could be used to detect all 7 guideline-recommended predic- tive biomarker mutations (EGFR, ALK, ROS1, BRAF, RET, MET, and ERBB2) and 1 prognostic biomarker mutation (KRAS) at the same rate as traditional tissue genotyping tests in 282 patients with newly diagnosed advanced NSCLC enrolled at 28 North American centers between July 2016 and April 2018. Of the 282 patients who submitted a pretreatment blood sample for cfDNA analysis, the majority were white (81.9%) and half were female (54.3%). Papadimitrakopoulou noted that clinical follow-up of the study is ongoing.

She concluded that the study validates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC. “What prompted the study was the desire to demonstrate that the liquid biopsy, which is easier to obtain and with a faster turnaround time, can detect these mutations and alterations in the DNA at a rate similar to the standard, which is tissue biopsy. That is something that is assumed to be true but was not tested in a clinical trial prospectively,” she added. “We felt there was a need for this since the desire to expand the group of patients who get these tests upfront is great. Having a test that we can rely upon to get good results for treatment choices is a very important step.”

REFERENCES

Leighl N, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC). Presented at: AACR Annual Meeting 2019 media preview; Feb. 27, 2019; Philadelphia.

Nurse Perspective

 Kim Parham BSN, RN, CN-BN Kim Parham BSN, RN, CN-BN
Quality Care & Clinical Relations, GO2 Foundation for Lung Cancer

THERE IS HOPE THAT A QUICK and easy blood biomarker diagnosis of metastatic lung cancer will become standard of care. With the research just released at the 2019 American Association for Cancer Research meeting, Vassiliki A. Papadimitrakopoulou, MD, presented encouraging results of a liquid biopsy test’s speed and accuracy. If liquid biopsy becomes standard of care, it will be much more convenient for patients to have blood taken in the doctor’s office or while in the hospital. In this study, the turnaround time for test results was 6 days faster than for normal tissue biopsies. Shared decision-making discussions based on molecular profiles could be discussed and appropriate targeted medications started in a timely manner. Currently, many patients start chemotherapy and/ or immunotherapy without obtaining molecular testing results. But liquid biopsy could be a process improvement for hospitals and physician practices looking to shorten their time from diagnosis to treatment initiation. Nurses have the challenge of keeping up with new actionable markers and their subtypes, medi- cations, adverse events, adherence, and financial assistance programs. In fact, many facilities are starting to institute separate molecular tumor board discussions to help the entire healthcare team stay current with advances in testing and medications. With many liquid biopsies beginning to demonstrate validated research, hope is on the horizon.
Colorectal Cancer

Younger Patients With CRC Are Misdiagnosed, Diagnosed at Later Stages


Brielle Benyon

Many younger patients with colorectal cancer (CRC) see multiple doctors and face misdiagnoses before their cancer is correctly diagnosed, according to research presented in conjunction with the American Association for Cancer Research Annual Meeting 2019.1 Also, younger patients often don’t see a doctor promptly after symptoms develop, sometimes waiting up to a year. The Colorectal Cancer Alliance conducted a comprehensive survey of young-onset patients and survivors to gather further information about their clinical, psycho- social, financial, and quality-of-life experiences.

Investigators found that 71% of respondents received diagnoses at stage III/IV in contrast to patients over the age of 50, who are “significantly more likely” to receive diagnoses at stage I/II. She said. “We do not yet know the cause, and there is little awareness of this trend among healthcare providers.” The US Preventive Services Task Force recom- mends that adults aged 50 to 75 be screened for colorectal cancer, and the American Cancer Society now recommends that regular screenings begin at age 45.

Yarden said that if individuals have a family history of CRC, they should start screenings at age 40. The study found that 63% of patientsunder age 50 waited 3 to 12 months before seeing a physician about their symptoms, often because they did not recognize them as signs of CRC. In addition, 67% saw at least 2 physicians before receiving a CRC diagnosis. Some patients passed through as many as 4 physicians before a CRC-confirming diagnosis.

Initial misdiagnoses were at fault in many of these cases, leading to treatment delay. Only one-third (33%) received diagnoses after seeing 1 doctor; 40%, after seeing 2 doctors; 16%, after 3; and 11%, after 4. The problem may be that CRC is not generally considered a disease affecting younger patients, said Ronit Yarden, PhD, MHSA, lead study investigator and director of medical affairs at the Colorectal Cancer Alliance. “Traditionally, colorectal cancers have been associated with aging.” Up until recently, guidelines called for initiating CRC screening at age 50, which Yarden said contributed to a reduction in incidence and mortality from CRC among elderly patients.

Conversely, the incidence of CRC among younger individuals is on the rise, Yarden said, explaining that for every 10 CRC diagnoses in the United States, 1 will be in a patient who is under the age of 50. “There has been a rapid and alarming rise in colorectal cancer inci- dence among young adults in recent decades.”

Investigators reviewed 1195 online surveys completed by individuals who received a diag- nosis of CRC before the age of 50 and found that 57% received such diagnoses between the ages of 40 and 49; 33%, between 30 and 39; and 10%, before 30. Thirty percent had a family history of CRC, and 8% had Lynch syndrome, which can be a genetic predisposition to the disease. One-fourth of the diagnoses were rectal cancer, and the rest were colon cancer.

Signs of CRC can easily be misinterpreted, Yarden conceded. Constipation, weight loss, and fatigue can be associated with many other conditions. “Physicians may attribute patients’ symptoms to more common conditions, such as hemorrhoids or inflammatory bowel syndrome, and may lack the urgency to refer patients for tests that may identify early-stage colorectal cancer,” she said.

“Both the medical community and the general population should be aware that colorectal cancer, which is one of the most preventable diseases, could happen in young adults,” Yarden said.

REFERENCE

Yarden RI, Newcomer KL; Never Too Young Advisory Board, Colorectal Cancer Alliance. Young onset colorectal cancer patients are diagnosed with advanced disease after multiple misdiagnoses. Presented at: American Association for Cancer Research Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract 3347/13.

Nurse Perspective

 Julia Shutt, MSN, RN, OCN Julia Shutt, MSN, RN, OCN
Roswell Park Comprehensive Cancer Center

YOUNG ADULTS TEND TO lead busy lives between work and family, seemingly leaving little time to take care of themselves. With the occurrence of colorectal cancer increasing in adults younger than 50 years.

I agree with the American Cancer Society’s recommendation to lower the recommended age in colorectal screening guidelines. The oncology nurse should encourage family members of patients with colorectal cancer to be screened at a younger age. We can teach patients and family members about symptoms to be aware of and watch for. Other teaching topics should include healthy lifestyles with good nutrition, exercise, and routine physical examinations. Nurses should also encourage patients to go with their instinct if something doesn’t feel right instead of putting off the doctor visit.

Young adult patients may struggle with the inability to work and support their family because of their disease or adverse events from treatment. Nurses can get a financial counselor involved or contact the social work department to help the patient explore helpful options.

Additionally, individuals may also feel guilty if they are not able to engage in intimacy in their relationship as a result of pain, fatigue, or other symptoms. Some may be embarrassed about having an ileostomy or colostomy.

The oncology nurse can provide emotional support by listening to these concerns and giving advice on how to cope. An example may be to cover the ostomy during intimate times with their significant other. Support groups are available and should be encouraged so patients going through similar situations can discuss what does or does not work for them and how they overcome difficult situations. A psychology referral may also help.

As oncology nurses, we are beginning to see a younger population overall with all forms of cancers. When patients are similar in age to the nurse caring for them, even more compassion and understanding are brought out in the nurse.

 
Leukemia

Gilteritinib Improves OS in Relapsed/Refractory FLT3+ AML


Gina Columbus

Gilteritinib (Xospata) improved overall survival (OS) in patients with relapsed/ refractory FLT3 mutation–positive acute myeloid leukemia (AML), according to updated findings of the phase III ADMIRAL trial.

The median OS in patients treated with the FLT3 inhibitor was 9.3 months (95% CI, 7.7-10.7) compared with 5.6 months in those who received salvage chemotherapy (95% CI, 4.7-7.3), leading to a 36% reduction in the risk of death (HR, 0.637; 95% CI, 0.490-0.830; P = .007).1

Complete response (CR)/CR with hematologic recovery (CRh) rate more than doubled with gilteritinib versus chemotherapy, at 34% and 15%, respectively. Patients on gilteri- tinib also had higher rates of allogeneic hematopoietic stem cell transplant (HSCT) than those on salvage therapy, at 26% versus 15%, respectively.

Forty percent to 70% of patients with AML relapse following remission with induction chemo- therapy, and up to 40% of patients are refractory to induction therapy and do not achieve CR. FLT3 mutations are detected in approximately 30% of patients with AML; FLT3–internal tandem duplica- tion (ITD) mutations confer an increased risk for early relapse and poor survival.

Gilteritinib is an oral, potent type I FLT3 inhib- itor designed to elicit activity against FLT3-ITD and FLT3-TKD D835 mutations. Prior ADMIRAL data showed that in 138 adult patients with FLT3 mutation–positive relapsed/refractory AML who received gilteritinib, the CR/CRh rate was 21% (n = 29; 95% CI, 14.5%-28.8%) at a median follow-up of 4.6 months.2

In the international, phase III ADMIRAL study, 371 adult patients with FLT3-mutant relapsed/ refractory AML were randomized 2:1 to receive gilteritinib 120 mg daily (n = 247) or salvage chemotherapy (n = 124). Patients in both arms then underwent HSCT, but only patients in the gilteritinib arm resumed treatment with the FLT3 inhibitor; crossover was not permitted. Salvage chemotherapy was selected prior to randomiza- tion and could be 1 of the following regimens: mitoxantrone, etoposide, and cytarabine; fluda- rabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor; low-dose cytarabine; and azacitidine (Vidaza).

Eligible patients must have also harbored an FLT3-ITD or FLT3-TKD mutation, had a mean of triplicate Fridericia-corrected QT interval <450 milliseconds at screening based on central reading, and been refractory to induction chemo- therapy or in untreated first relapse.

The majority of patients had intermediate-risk cytogenetics (73%), and 88% of patients had FLT3-ITD mutations. Additionally, 20% of patients had undergone prior HSCT, and 82% had received up-front intensive chemotherapy. Thirty-nine percent of patients had primary refractory AML without HSCT, and 27% relapsed ≤6 months after composite complete remission (CRc).

Co-primary endpoints were OS and CR/CRh rate; secondary endpoints were event-free survival, CR rate, leukemia-free survival, duration of remis- sion, CRc rate, transplantation rate, brief fatigue inventory, CRh rate, transfusion conversion rate, and transfusion maintenance rate.

In the intention-to-treat population (n = 371), the 1-year OS rates were doubled, at 37% (95% CI, 31%-44%), compared with salvage chemo- therapy, at 17% (95% CI, 10%-25%).

The CR, CRh, CRc with incomplete hematologic recovery, and CR with incomplete platelet recovery rates with gilteritinib compared with salvage chemotherapy were 21% versus 11%, 13% versus 5%, 26% versus 11%, and 8% versus 0%, respectively. Additionally, the CRc rate was 54% with gilteritinib and 22% with salvage therapy.

The overall response rates were 26% with salvage chemotherapy and 68% with gilteritinib and included a 13% partial response rate.

The median duration of gilteritinib exposure was significantly longer than that of salvage therapy, at 4.1 months (range, 0.1-29.1) and 0.9 months (range, 0.2-7.1), respectively. The median time to achieve CRc was 1.8 months (95% CI, 0.9-9.95) with gilteritinib and 1.1 months (95% CI, 0.8-2.9) with salvage treatment. The median duration of response with gilteritinib was also significantly longer compared with salvage therapy (11.0 months vs 1.8 months, respectively).

All-grade treatment-emergent adverse events were comparable between arms during the first 30 days of treatment; however, there were higher rates of increased levels of alanine aminotrans- ferase and aspartate aminotransferase with gilteritinib, which were generally of grade 1/2. There were equal rates of anemia (33%), and salvage therapy compared with gilteritinib had higher rates of febrile neutropenia (32% vs 21%), pyrexia (26% vs 15%), nausea (30% vs 13%), hypokalemia (27% vs 11%), and diarrhea (28% vs 10%, respectively).

Combining gilteritinib with frontline therapy in patients with FLT3-mutant AML may further improve outcomes. These include a phase I trial of gilteritinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed AML and a phase II/III study of gilteritinib alone, azacitidine alone, or the combi- nation of gilteritinib and azacitidine in patients with FLT3-mutant AML who are unable to receive standard chemotherapy.

REFERENCE

1. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib significantly prolongs overall survival in patients with FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML): results from the phase III ADMIRAL trial. Presented at: 2019 American Association for Cancer Research Annual Meeting; March 29-April 3, 2019; Atlanta, GA. Abstract CTPL04. 2. Xospata [prescribing information]. Northbrook, IL: Astellas Pharma US Inc; 2018. bit.ly/2SjB8CL. Accessed April 1, 2018.

Nurse Perspective

Diane Bartella, MSN, RN Diane Bartella, MSN, RN
Roswell Park Comprehensive Cancer Center

GILTERITINIB HAS POTENTIAL FOR PATIENTS with relapsed/refractory FLT3- positive acute myeloid leukemia (AML). Nurses can educate patients that this drug has fewer adverse events (AEs) than standard treatment. Although one AE of gilteritinib is elevated liver enzymes, the incidence of more severe AEs, such as neutropenic fever, nausea, vomiting, hypokalemia, and diarrhea, was found to be lower than that in patients who received standard salvage chemotherapy. Additionally, patients achieved count recovery earlier than those on salvage therapy. With this information, nurses should anticipate a decrease in AEs and improved blood counts earlier.

Nurses should stress the importance of oral adherence and of notifying providers of missed doses. Follow-up to monitor adherence might prove helpful. Nurses can also educate patients on tools that can help remind them to take their medication.

They should document conversations with patients regarding difficulties in obtaining or taking the drug, and collaboration with members of the healthcare team and other disciplines should be priority to ensure that patients are able to pay for and access the drug. In addition to oral adher- ence, nurses should also stress monitoring of liver enzymes and adhering to appointments because of the potential for elevated alanine aminotransferase and aspartate aminotransferase.

Patient education for patients taking oral gilteritinib is crucial for the overall survival rate in patients with relapsed/refractory FLT3-positive AML. Nurses should anticipate earlier and better outcomes for patients receiving this drug.

 

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