Selpercatinib (Retevmo) was recently approved for 2 new solid tumor indications. The kinase inhibitor was granted regular approval for locally advanced or metastatic 

 fusion–positive non–small cell lung cancer (NSCLC).

 It was also granted accelerated approval for patients with solid tumor harboring a 

Selpercatinib had previously received accelerated for 

-fused NSCLC approval based on initial findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128). Confirmatory data from an additional 172 patients and 18 months of extended follow-up secured the agent’s full approval. Updated findings showed that patients with 

-positive NSCLC achieved a 61% overall response rate (ORR), a complete response rate (CR) 7.3% and a partial response (PR) rate of 54%. In addition, the median duration of response was 28.6 months (95% CI, 20–not estimable [NE]) and 63% achieved a response which lasted for 12 months or longer.

The accelerated approval was supported by findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128), which showed that that the targeted therapy yielded an ORR of 44% (95% CI, 28%-60%) in patients with 

-fusion solid tumors, as well as a 4.9% complete response, and a 39% partial response rate. In this trial, the median duration of responses was 24.5 months (95% CI, 9.2-NE), and 67% of patients achieved a response that lasted for at least 6 months.

Patients who achieved responses included those with pancreatic adenocarcinoma, colorectal cancer, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

In terms of testing, in the population of patients with NSCLC, 94% of 

-fusions were identified with next-generation sequencing (NGS), 84.6% were confirmed with a tumor sample, 9.3% were found with a blood or plasma sample, 4.0% were detected with FISH, and 1.6% through PCR. In addition, 0.4% had their mutation tested through another method. In solid tumors, 97.6% of 

-fusions were detected via NGS, and 2.4% of these fusions were detected through FISH.

Selpercatinib comes in 40 mg and 80 mg capsules. For patients weighing less than 50 kg, the recommended dose is 120 mg twice a day. For those who are greater than 50 kg, the recommended dose is 160 mg twice a day. If a patient has severe hepatic impairment, they should receive a reduced dose.

Providers should avoid coadministering with acid-reducing agents, strong and moderate CYP3A inhibitors or inducers, CYP2C8 and CYP3A substrates, and certain P-gp substrates. If acid-reducing agents are necessary, then selpercatinib should be taken with food and the administration time should be modified. If strong or moderate CYP3A inhibitors cannot be avoided, the selpercatinib dose should be reduced. If a patient required CYP2C8 and CYP3A substrates, or P-gp substrates, the substrate dosages should be reduced, as recommended in their product labeling.

There are no contraindications, however, the agent comes with warnings for hepatotoxicity, interstitial lung disease (ILD), hypertension, hemorrhagic events, hypersensitivity, tumor lysis syndrome, hypothyroidism, and risk of impaired wound healing. The drug also increases the risk for embryo-fetal toxicities.

For hepatotoxicity risk, the label advice monitoring alanine aminotransferase (ALT) and aspartate aminotransferase (AST), prior to initiation selpercatinib and monitoring every 2 weeks during the first 3 months, followed by monthly monitoring as necessary.

Patients with uncontrolled hypertension should not initiate selpercatinib. All patients should have their blood pressure optimized prior to starting treatment and should be monitored at their first week of treatment and monthly thereafter. Thyroid function should also be assessed at baseline and periodically throughout treatment.

Patients should be evaluated for QT interval, electrolytes and thyroid stimulating hormone at baseline, and periodically throughout treatment. If patients require concomitant treatment with strong and moderate CYP3A inhibitors, minoring should be even more frequent.

Because selpercatinib increases the risk of impaired wound healing, it should be withheld for at least 7 days prior to elective surgery. Following major surgery, patients should not receive this agent for at least 2 weeks and until their wounds have adequately healed. The safety of agent resumption following wound healing complications are not yet established.

In addition, if a patient developed hypersensitivity, the agent should be withheld, and corticosteroids should be initiated. Upon resolution, treatment should be resumed at a reduce dose and increased by 1 dose level each week until the dose is the same as it was prior to the onset of the reaction. Once the target dose has been reached, tapering can begin.

Based on the severity of possible hepatotoxicity, ILD, hypertension, or QT interval prolongation, the agent should be withheld, dose reduced, or permanently; discontinued.

The most common any-grade adverse events associated with selpercatinib include edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities include decreased lymphocytes, increased ALT, increased AST, decreased sodium, and decreased calcium.

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. News release. FDA. September 21, 2022. Accessed September 21, 2022. 

FDA approves first therapy for patients with lung and thyroid cancers with a certain genetic mutation or fusion. News release. FDA. May 8, 2020. Accessed September 21, 2022. 

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. September 21, 2022. Accessed September 21, 2022. 

Retevmo. Prescribing information. Eli Lilly and Company; 2022. Accessed September 21, 2022. 

Articles

Selpercatinib was approved by the FDA for RET fusion–positive non–small cell lung cancer and locally advanced or metastatic RET fusion–positive solid tumors. 

Selpercatinib Is Approved for 2 RET Fusion–Positive Solid Tumors, Non–Small Cell Lung Cancer

The addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) elicited promising overall survival (OS) and progression-free survival (PFS) outcomes in patients with hormone receptor–positive, HER2-negative early breast cancer. The survival benefit was observed in the intention-to-treat (ITT) population and across subgroups of patients with visceral disease (sVD), according to findings from the second interim prespecified OS analysis of MONARCH 3 trial (NCT02246621).

Results of this analysis showed there to be an increase in the median OS by over 12 months with the addition of abemaciclib to NSAI. However, neither the ITT or sVD populations met the threshold for formal statistical significance.

Findings showed that with a median follow-up of 26.7 months, PFS for those receiving abemaciclib plus NSAI was 28.2 months vs 14.8 months with placebo plus NSAI (HR, 0.540; 95% CI, 0.418-0.698; 

 =.000021). At this time, OS was immature with 29.5% observed between each arm of the study.

At the time of this second interim analysis with a data cutoff of July 2, 2021, the median OS for the ITT population was 67.1 months for those receiving abemaciclib plus NSAI vs 54.5 months for those administered placebo plus NSAI (HR, 0.754; 95 CI, 0.584-0.974; P =.0301).

In the ITT population and with a median follow-up of 5.8 years, the median PFS for those in the abemaciclib plus NSAI arm was 29.0 months vs 14.8 in the placebo plus NSAI arm (HR, 0.518; 95% CI, 0.415-0.648; 

 <.0001). There are also more patients remaining progression-free at 5 years in the abemaciclib plus NSAI arm at 26.7% vs those in the placebo plus NSAI arm at 9.6%.

The chemotherapy-free survival for patients in the ITT population was also higher with abemaciclib plus NSAI at 46.7 months vs 30.6 months for placebo plus NSAI (HR, 0.636; 95% CI, 0.505-0.801).

For the subgroup of patients with sVD in the second interim analysis, the median OS was 65.1 months with abemaciclib plus NSAI vs 48.8 months with placebo plus NSAI (HR, 0.708; 95 CI, 0.508-0.985; 

 =.0392). Although statistical significance was not reached, these data are still maturing favorably with a 16.3-month difference in median OS (HR, 0.708; 95% CI, 0.508-0.985).

Findings 3 were presented at the ESMO 2022 Congress by Matthew Goetz, MD, chair of the Breast Cancer Disease-Oriented Group and coleader of the Women's Cancer Center at the Mayo Clinic in Rochester, Minnesota.

“At this second interim analysis, a numerically favorable overall survival difference was observed in both the intent-to-treat population, as well as this subgroup of patients with visceral disease. Although neither group met the threshold for stopping or for statistical significance due to the alpha spending procedure, in the ITT population, this was a greater than 12-month difference, and in the visceral disease population, this was greater than 16 months. Consistent overall survival differences were observed across the pre-specified subgroups, abemaciclib delayed subsequent receipt of chemotherapy, and we saw no new safety signals,” said Goetz in a presentation of the data.

Abemaciclib is an oral, potent, CDK4/6 inhibitor and is the first of its kind to be approved in advanced breast cancer and in combination with endocrine therapy for the adjuvant treatment of high-risk, hormone receptor–positive, HER2-negative early breast cancer.

Previously, data from the MONARCH 2 led to the approval of abemaciclib in combination with fulvestrant (Faslodex) in patients with hormone receptor–positive, HER2-negative advanced breast cancer who progressed on prior endocrine therapy. A significant improvement in OS for the combination was demonstrated in the trial, leading to the start of the MONARCH 3 trial.

In the randomized, double-blind, placebo-controlled, phase 3 MONARCH-3 trial, the combination of abemaciclib and an NSAI was examined in postmenopausal women with hormone receptor–positive, HER2-negative metastatic or locally advanced breast cancer.2

Enrollment was open to women aged 18 years and older with hormone receptor–positive, HER2-negative breast cancer with locoregionally recurrent disease that could not be fixed by resection or radiation therapy with curative intent or metastatic disease. Other requirements were to be postmenopausal, either measurable disease or nonmeasurable bone-only disease, an ECOG performance status of 0 to 1, adequate organ function, and the ability to swallow capsules. Additionally, patients must have discontinued previous localized radiotherapy.

The primary end point of the study was investigator-assessed PFS with secondary end points including OS, percentage of patients with complete response, partial response, or stable disease, duration or response, pharmacokinetics, and safety.

A total of 493 patients were randomized 2:1 to receive either 150 mg of abemaciclib twice a day plus 1 mg of anastrozole or 2.5 mg of letrozole daily (n = 328), or placebo plus the same dosages of anastrozole or letrozole (n = 165).

Regarding safety, no new safety signals were observed with long-term use of abemaciclib. A total of 323 patients (98.8%) in the abemaciclib plus NSAI arm had at least 1 treatment emergent adverse event (TEAE) of any grade vs 152 patients (94.4%) who were given placebo plus NSAI. The most common any grade TEAEs for those given abemaciclib were diarrhea (83.2%), neutropenia (46.8%), and fatigue (44.3%). The most common grade 3 and greater TEAEs in this arm were neutropenia (27.2%), diarrhea (9.8%), and anemia (8.9%).

Overall, these updated findings showed there to be a longer OS observed in both the ITT and sVD populations and safety data were consistent with the known profile of abemaciclib.

“The final OS analysis is planned after at least 315 events in the ITT and at least 189 events in the visceral disease subgroup. We anticipate that the final overall survival data should be read out in 2023,” Goetz said.

Goetz MP, Toi M, Huober J, et al. MONARCH 3: interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC). Presented at: 2022 ESMO Congress; September 9-13, 2022; Paris, France;

A study of nonsteroidal aromatase inhibitors plus abemaciclib (LY2835219) in postmenopausal women with breast cancer (MONARCH 3). ClinicalTrials.gov. Updated July 27, 2022. Accessed September 8, 2022. https://clinicaltrials.gov/ct2/show/NCT02246621

For patients receiving an aromatase inhibitor for hormone receptor–positive, HER2-negative breast cancer, the addition of abemaciclib doubled median progression-free survival vs placebo.

Addition of Abemaciclib to Aromatase Inhibitor Therapy Prolongs Survival in HR+/HER2- Breast Cancer

Videos

A broad overview of the treatment armamentarium for patients receiving first- or second-line therapy for HER2+ gastric cancer.

First- and Second-Line Treatment Options for HER2+ Gastric Cancer

Focused discussion on the management of antibody drug conjugate–related adverse events in gastric cancer, with a focus on neutropenia. 

T-DXd in HER2+ Gastric Cancer: Managing Neutropenia and Other AEs 

Cannabinoids are becoming more popular for patients with cancer as a pain management strategy. However, with inconsistent laws across states and federal bodies, it can be difficult for nurses and patients to comfortably discuss cannabinoids and cannabinoid use.

As the public perception and patient success stories with unconventional, alternative, and natural therapeutics shift consumer attitudes, it is important for nurses and their patients to understand the differences in the products and the adverse effects associated with each. According to a study by Butler et al in 2021, nearly half of individuals who participated in a survey who had consumed cannabidiol (CBD) did not disclose use to their health care provider.

“We see a lot of patients who have been trying to talk to us about CBD [cannabidiol], and cannabinoids and THC, [tetrahydrocannabinol]” Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, a professor of nursing at Vanderbilt University School of Nursing, said in a presentation during the Oncology Nursing Society Bridge.

Although Hande stated in her presentation that she was no expert in cannabinoids or medical cannabis, her clinical research primarily focuses on helping patients effectively manage their cancer-related pain. Therefore, she has become very interested in cannabis and has dedicated a lot of time and research to best understand the evidence-based data that exists for these products. In her presentation, “Cannabinoids for Patients With Cancer,” Hande discussed the available evidence on CBD and the possible risks, particularly in vulnerable populations.

“I think it’s just important for under us to understand a kind of broad overview about cannabinoids and THC and CBD, because this gives us a better understanding of where the laws come into play,” Hande said. She added, “It took me quite some time to try to understand all the differences and trying to make sure I give the correct information to my patients.”

A key concept for oncology nurses to understand, according to Hande, is the variations of cannabinoids.

Cannabinoids are compounds found in the cannabis plant. These compounds interact with the human endocannabinoid system. The exact relationship still required further understanding.

“Cannabis has many names for [many] strains, and hemp and marijuana are under this big umbrella of cannabis plants; they are all considered to be 1 species: the cannabis sativa plant,” she said. “This is a genus of flowering plants. And these can contain about over 100 phytocannabinoids, [and] they have a wide range of effects on the body in the brain.”

The following products are derived from cannabis: marijuana, hemp, THC, and CBD. In addition, there are man-made synthetic cannabinoids (K2/Spice); however, these agents are designed to mimic the mind-altering effects of illicit drugs. For her talk, Hande chose to focus on the products derived from the plant itself, as oncology nurses are more likely to encounter patients using plant-derived products.

If a patient reports marijuana use, this means they are using the dried flowers, leaves, stems, and seeds of the cannabis plant. Marijuana is also known as cannabis, weed, pot, or dope. Specifically, it can be defined as a plant with at least 0.3% delta-9 THC by weight. It is consumed by smoking (joints, blunts, bongs), vaping (vaporizing electronics devices), or by mixing or infusing it into foods or drinks (edibles).

“This is an important differentiating factor that I’ll be highlighting regularly through this talk,” Hande said during her presentation. “Marijuana is more than 0.3% of THC by weight.”

Marijuana is the most used federally illegal drug in the United States, with approximately 18% of Americans reported using it at least once in 2019 (~48.2 million Americans).1

Because marijuana has THC, it is associated with the following health risks: alterations in memory, learning, attention, decision-making, coordination, emotion, and reaction times.2 In terms of long-term health, marijuana has been linked to an increased risk of psychosis and schizophrenia,3 and, like other drugs, it’s use during pregnancy may increase the risk of embryo-toxicities.4 Moreover, this drug, depending on where it is sourced, may be laced with other substances. Consumers may or may not be aware of other substances in their product.

Using marijuana in combination with other agents may also result in impairment and can increase the risk of overdose.

Federally, marijuana is illegal as a recreational drug. It is classified as a schedule 1 drug, per the Drug Enforcement Agency. Although it is legal in some states for medical for nonmedical adult use, this does not mean that is safe, Hande noted. Specifically, smoking marijuana can expose users to harmful chemicals, and insufficient evidence exists to document the safest method for consuming.

Legally, hemp must contain a THC concentration of less than 0.3% by dry wright. It is the same species of plant as the cannabis plant and, along with bamboo, it is one of the fastest growing plants on Earth. There are almost no restrictions on hundreds of compounds made by the plant. Industrial hemp is cannabis sativa plant grown specifically for industrial or medicinal use.

“Many states across the country have hemp cultivation,” Hande said. “This allows cultivation of hemp from commercial or research or pilot programs. There are only a few states that do not allow cultivation of hemp.”

In 2018, the farm bill legalized the production and sale of hemp and its extracts, removing the product from the controlled substance act. Of note, per federal law, hemp cannot contain greater than 0.3% THC. If the concentration of THC surpasses this measurement, it is classified as marijuana.

As of September 2022, 47 states have enacted legislation to establish hemp production programs or cultivation research.

THC is a compound of the cannabis plant. This psychoactive agent causes, what is known as a high. It is consumed via dabbing—a specific method for inhaling THC concentrates.

Unfortunately, the concentrated forms of THC mean that there is an increased risk of additives or contaminating substances existing in the product.

CBD is another active cannabinoid found in the cannabis plant. This agent is not psychoactive and consequently does not cause a high.

CBD can be derived either directly from the cannabis plant or from a hemp product. The key difference between cannabis- and hemp-derived CBD is the concentration of THC. Hemp-derived CBD must have a THC concentration less than 0.3% to be federally legal. CBD products containing greater concentrations are federally illegal but are legal under some states.

“The main difference between cannabis and hemp-derived CBD is the amount of THC that it can contain,” Hande stressed. “Hemp-derived CBD includes less than 0.3% of the THC. [Therefore,] it’s federally legal to use hemp-derived CBD, but CBD products that contain more than 0.3% of THC are federally illegal. This is where the conflict between the state and the federal laws [can arise].”

The extraction process for CBD and THC are similar; farmers harvest the hemp and it is sent to an extractor. If the extraction is not performed with pharmaceutical grade standards, the CBD may become contaminated with THC, chemical solvents, or even pesticides. This is compounded by the fact that the US does not hold CBD supplies to a standard, and federal enforcement is lacking.

CBD can be converted into delta-8-THC, delta-9 THC, and other THC isomers through a solvent, acid, and heat. These products end up with higher concentrations of delta-8 THC than those which occur naturally in the cannabis plant. Consequently, these products may create harmful by-products that presently are not well-characterized.

Delta-8 THC products are increasing in popularity, in both marijuana- and hemp-based markets. It is appearing in markets that are operating legally under state, territorial, or tribal laws.

As of 2022, most states and territories permit full and restricted marketplaces where consumers can purchase hemp and hemp-derived CBD products.

According to Hande, there are a wide variety of delta-8 THC-containing products in the market. For example, vapes, smokable hemp sprayed with delta-8 THC extract, distillates, tinctures, gummies, chocolates, and even infused beverages can fit into this category. Moreover, the testing method for these products are still under development. This means that Delta-8 THC products may not be systematically tested for contaminants such as heavy metals, solvents, or pesticides which can cause adverse health effects.

How to Talk to Your Patient About Cannabinoid Use

Nurses hold a key role in discussing not only the risks of cannabinoid use but providing educational information for the safe consumption. Should a patient be interested in trying CBD products, counsel on the lack of evidence, contaminants, misleading labels, and legal issues of surrounding use. One approach to counter the “buyer beware” notion is to provide evidence-based patient education and to screen for any drug/drug interactions that may occur should the patient consume CBD products.

Additionally, assessing the patient’s baseline knowledge base before use will be beneficial and open communication may help establish trust and increase reported use between the patient and the health care provider. Finally, addressing the topic early on in care may remove the barrier of the stigma surrounding cannabinoid use.

Hande concluded by adding that many trials are ongoing in the cannabinoid arena and that results are expected to be published over the next several years. She noted that the oncology nurses should be up-to-date on the latest findings to provide guidance.

Marijuana and public health data and statistics. Centers for Disease Control and Prevention. June 8, 2021. Accessed September 14, 2022. bit.ly/3ROqaoi

Testai FD, Gorelick PB, Aparicio HJ, et al. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. 

. 2022;53(4):e176-e187. doi:10.1161/STR.0000000000000396

Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. 

. 2019;6(5):427-436. doi:10.1016/S2215-0366(19)30048-3

Health effects of marijuana and cannabis-derived products presented in new report. National Academies. January 12, 2017. Accessed September 14, 2022. 

Karen Hande, PhD(c), DNP, ANP-BC, CNE, FAANP, ANEF, explains the difference between some of the popular cannabinoid products that patients with cancer may be taking.

Oncology Nurses: What Cannabinoid Is Your Patient Taking?

® spoke with Christine Miaskowski, PhD, RN

professor in the Department of Physiological Nursing and Anesthesia at UCSF School of Nursing. Miaskowski discusses results from research which showcases an increased risk of hearing loss among patients who received platinum- or taxane-based cancer treatments. She also discusses the importance of including hearing assessments as a standard of care for survivors.

Top takeaways from the discussion include:

“When we did audio metrically confirmed hearing loss [assessments], we found that between 50% to 70% of survivors had confirmed hearing loss.” 

“It’s really, very surprising because it is a group of patients with very common cancers: breast, lung, gynecologic and GI [gastrointestinal] malignancies.” 

“The good news is that the type of hearing loss these patients experience is amenable to a hearing aid. So, if we can get people tested, and they demonstrate this kind of hearing loss, we can improve their quality of life.” 

“Nurses care about interactions with other people, people’s quality of life, [their] social function… if you've got hearing loss, and you're sitting at a table with people, and you can't hear them, you're not going to be likely to participate.” 

“We don’t even think about [some of] these consequences; in terms of occupation, social gatherings, safety for a child… We really, as nurses, need to be doing something about this.” 

Episode 33: Balancing the Benefit and Toxicity of Cisplatin in Young Children with Cancer

Episode 45: Key Advances in Cancer Survivorship Toxicity Management

Audiological Assessments May Be Vital Component of Cancer Survivorship Care Following Chemotherapy

Hearing Loss Found in Testicular Cancer Survivors After Cisplatin Therapy

Genetic Mutation Could Play Role in Cisplatin-Induced Hearing Loss

Oncology Nursing News® Publication Features

Survivors Need Research-Based Interventions and Stronger Coordination Across Care Continuum

What Are the Needs of Cancer Survivors 5 Years or More After Treatment?

Everyone's Business: Taking Survivorship Care to the Next Level

Heather E. Wheeler Discusses Cisplatin-Induced Hearing Loss

Cheung S, Henderson-Sabes J, Mastick J, et al. Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus. 

. Published online July 27, 2022. doi:10.1136/spcare-2022-003684

Romano A, Capozza MA, Mastrangelo S, et al. Assessment and management of platinum-related ototoxicity in children treated for cancer. 

2020;12(5):1266. doi:10.3390/cancers12051266

Biro K, Noszek L, Prekopp P, et al. Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission. 

. 2006;70(3):177-184. doi:10.1159/000093776

Cheraghi S, Nikoofar P, Fadavi P, et al. Short-term cohort study on sensorineural hearing changes in head and neck radiotherapy

2015;32(7):200. doi:10.1007/s12032-015-0646-3

Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. 

. 2013;34(8):458-469. doi:10.1016/j.tips.2013.05.006

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Podcasts

In this episode of “The Vitals,” Christine Miaskowski, PhD, RN, discusses research showcasing that adult patients receiving either a platinum-based chemotherapy, taxane alone, or a combined regimen of platinum- and taxane-based treatment may be at risk of hearing loss. 

Are Hearing Tests Necessary For Adult Cancer Survivors?

Before closing out their discussion on antibody drug conjugate use in breast cancer management, panelists consider ongoing clinical trials in this setting. 

A Brief Review of Ongoing Clinical Trials of ADCs in Breast Cancer

Centering discussion on a patient profile of HER2+ gastric cancer, experts in oncology discuss the occurrence of neutropenia with trastuzumab deruxtecan therapy.

Patient Profile 3: A Patient with HER2+ Gastric Cancer Treated With T-DXd–who Develops Neutropenia 

Most adolescent or young adults with advanced cancer prefer to die at home, according to results of a qualitative interview study published in 

 Unfortunately, the desire of many of AYA patients is not realized with up to two-thirds of AYAs passing away in the hospital setting, underscoring an unmet need regarding death preferences in this population.

“Our data suggest a preference for home death for most AYAs with advanced cancer,” wrote Oreofe O Odejide, MD, assistant professor of medicine and medical oncology at the Dana-Farber Cancer Institute, and co–investigators.

“Unfortunately, this preference is aspirational for many, as the majority die in hospital settings. To ensure that the EOL [end-of-life] experiences of AYAs align with their preferences, robust home-based services for symptom control and logistical/psychosocial support for family caregivers and siblings are imperative: we need innovative strategies that close the gap between preferred and actual location of death to achieve high-quality EOL care for AYAs with cancer.”

In the US, more than 9000 AYA patients die of cancer every year, and existing data suggests that EOL care for may be less than optimal in this population. High-intensity care, frequent hospitalizations, intensive care unit admission, and chemotherapy in the last month of life can all contribute to negative EOL experiences. These are more likely to occur for AYA patients than with older adults or young children. Moreover, most AYA patients die in the acute-care setting. Findings from a 2021 study published in 

 estimated that 69% of AYA patients pass away while admitted.

Investigators sought to better understand patient preferences—specifically, preferential EOL locations.1 Therefore, they conducted quantitative interview studies of AYA patients with advanced disease and compiled responses along with the responses of their family caregivers and clinicians. Interviews occurred between December 6, 2018, and January 5, 2021. Eligible participants were identified from clinical lists, administrative databases, and clinician referrals. The study included a total of 80 individuals: 23 patients, 28 family caregivers, and 29 clinicians.

The interviews revealed that multiple factors influence an AYAs choice of death location. The driving rationale comes from a want to be around family and friends but other reasons for include a desire for comfort, a sense of normalcy, and wanting to be protected from the isolation of being in the hospital.

One participant stated: “Rather than being in a situation where my last days are spent on a hospital bed and my parents and my loved ones have to come to the hospital, I would rather kind of share those experiences in the last days in a home – I would rather pass at home.”

External factors, however, may influence an AYA patient’s decision, and persuade them to elect an in-hospital death. One reason for this may be that there are more logistical considerations necessary for an at-home death. Caregivers were more likely to recognize these logistical considerations, which include need for pain and symptom management.

One caregiver described circumstances surrounding a patient that would influence admission to a hospital being preferential. “Had she experienced a tremendous amount of pain, we would have sought another way of you know either getting continuous IV [intravenous] morphine…or we would have brought her back to the hospital,” the caregiver responded. “And although she wouldn’t have wanted that decision, the pain decision would have superseded the decision to keep her home.”

A clinician backed that sentiment, noting, “Most [individuals] feel it would be nice to be at home, but then the question is: at what cost?… The symptom burden is high here—few [individuals] that I’ve met are willing to be at home at the cost of risk of symptom control.”

Moreover, there is the desire of the caregiver to preserve the home as a place “untouched” by death, particularly for the benefit of a sibling, which may persuade AYA patients to choose a hospital death. One caregiver acknowledged that her family did not want to “mar” their home space and did not want the patient’s younger sibling to witness her brother’s death.

Although most AYAs expressed that they would prefer to pass away at home, they also acknowledged a family member preference and, consequently, they expressed concern about imposing additional trauma on their family members if they choose to stay at home. The desire to experience EOL comfort for themselves, and the need to not to be a burden to their family, created a tension that was identified in the study. Results noted that many AYAs chose a hospital-death specifically to limit the potential burden on their family members.

Lastly, the need for hospice care is at odds with the desire to pass away at home. Although hospice care can be useful in facilitating an at-home death, there are limitations, and some families may opt to bring their loved one in for inpatient hospice care despite patient preferences. For example, a bereaved caregiver reported that their loved one died in a hospice house rather than at home because of inability to access the high level of care needed to facilitate a home death.

Another stated, “One thing I wish is that in-home hospice services would be able to do 24-hour care, not nursing care, but [provide an] aide to stay with the patient. Because I had to put him in a hospice house because he couldn’t die at home because I couldn’t care for him anymore. That was hard for me.”

Although at-home hospice services represent an interesting tactic to try and make at-home deaths feasible, gaps still remain in this type of care and will need to be expanded if families are truly able to take advantage of these services rather than inpatient hospice. Similarly, robust home-based services for symptom control and logistical/psychosocial support for family caregivers and siblings are imperative and warrant further investigation.

Given the stress that surrounds EOL experiences, seeking invocative solutions to improve the level of comfort for these patients is necessary, the authors concluded.

Odejide OO, Fisher L, Kushi LH, et al. Patient, family, and clinician perspectives on location of death for adolescents and young adults with cancer. 

Published online August 18, 2022. doi:10.1200/OP.22.00143

Coltin H, Rapoport A, Baxter NN, etc. Locus-of-care disparities in end-of-life care intensity among adolescents and young adults with cancer: a population-based study using the IMPACT cohort. 

 2022;128(2):326-334. doi:10.1002/cncr.33926.

Innovative strategies are needed to ensure that adolescents and young adults with cancer who prefer to die at home are able to make that choice.

Better End-of-Life Options Are Needed for AYA Patients With Advanced Cancer

Patients who received pembrolizumab (Keytruda) to treat early-stage, triple-negative breast cancer (TNBC) reported similar scores across global health score (GHS), function, and breast symptom domains, compared with patients who received placebo, according to a patient-reported outcomes (PROs) analysis of the KEYNOTE-522 (NCT03036488) trial presented during the 

2022 European Society of Medical Oncology Congress.

“Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in statistically significant and clinically meaningful improvement in pathological complete response [pCR] and event-free survival [EFS] vs neoadjuvant chemotherapy alone in patients with early-stage TNBC,” Rebecca Dent, MD, MSc, senior consultant at the National Cancer Center in Singapore, said in a presentation of the findings. “Together with the efficacy and safety findings of KEYNOTE-522, these PRO results support neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as an effective standard-of-care treatment regimen in this setting, without meaningful impact on health-related quality of life [HRQOL],” she added.

The KEYNOTE-522 study was designed to assess the efficacy of pembrolizumab in adults with newly diagnosed TNBC. Key eligibility criteria included a TNBC diagnosis with either T1c N1/2 or T2/4 N0-2 tumors, an ECOG performance status of 0 or 1, and a tissue sample for PD-L1 assessment.

The 1174 patients who enrolled were randomly assigned 2:1 to receive either pembrolizumab or placebo, plus chemotherapy, during the neoadjuvant phase, and monotherapy pembrolizumab or placebo in the adjuvant phase. During the neoadjuvant phase, which encompassed all treatments leading up definitive surgery, patients received carboplatin plus paclitaxel for the first 4 cycles, (12 weeks of treatment), followed by doxorubicin or epirubicin

plus cyclophosphamide for the next 4 cycles (12 weeks of treatment). Following surgery, patients received adjuvant treatment for 9 cycles (27 weeks). Those who received pembrolizumab were administered a dose of 200 mg once every 3 weeks.

The primary end points of the trial were pCR and EFS in the intention-to-treat population as assessed by a local pathologist. Secondary end points included PROs. To measure these, investigators leveraged the European Organization for Research and Treatment of Cancer Quality of Life Core 30 questionnaire (EORTC QLQ-C30) and EORTC QLQ-BR23, which are oncology-specific and breast cancer-specific, respectively, as well as the EuroQol-5D utility score EQ-5D. Patients were asked to complete these assessments before treatment for cycles 1 (baseline), 5, and 8 during the neoadjuvant phase. Following surgery, they were asked to complete the assessments every 12 months for 2 years or until disease progression or recurrence.

The differences in least squares mean change from baseline at primary analysis were assessed via a constrained longitudinal model. No alpha was assigned. For each PRO assessment, scores ranged from 0 to 100, and meaningful change was defined of a threshold change of greater than 10 points.

At data cutoff, the completion rate, or the number of patients who completed at least 1 score/term at each time point over the number of patients in the PRO full analysis set population, was greater than 60%. The compliance rate, or the number of patients who completed at least 1 score/item at each time point over the number of patients expected to complete at each time point, was greater than 80%.

In the neoadjuvant phase, at week 21, the percentage of patients who completed at least 1 PRO measurement was 80.7% in both the experimental (n = 762) and control arms (n = 383). The compliance rate between the 2 arms was 89.4% vs 88.5%, respectively. Moreover, following surgery, the completion rate between the pembrolizumab and placebo arms were 82.4% and 80.8%, respectively. The compliance rate was 91.7% vs 88.3%, respectively.

In the neoadjuvant phase of the trial, the LS mean score change from baseline (95% CI) was comparable between the 2 arms in GHS and QOL, with a mean change of –1.04 between the 2 arms (–3.46 to 1.38). Similarly, emotional functioning and physical functioning were similar affected, the mean changes was –0.69 (–3.13 to 1.75), and –2.85 (–5.11 to –0.60), respectively. In terms of breast cancer-specific symptoms, the mean change was –0.13 (–1.92 to 1.65), and changes in visual analog score (VAS) was –1.61 (–3.87 to 0.64).

These findings were also consistent with the adjuvant baseline scores. The LS mean changes score from baseline (95% CI) was –0.41 (–2.60 to 1.77) for GHS/QOL, –0.60 (–2.99 to 1.79) for emotional functioning, and –1.57 (–3.36 to 0.21) for physical functioning. The mean change for breast cancer-specific symptoms was 0.29 (–2.05 to 2.63) and the mean change in VAS was –0.59 (–2.40 to 1.23).

“These [data] are an important component of this trial [because] we have an arm of patients who are not getting an active drug,” Dent noted. “The mean scores are similar between the 2 groups; no meaningful difference from the baseline, and again, this is across all the domains and all the scales that were measured: quality of life, emotional functioning, physical functioning, [and] breast symptoms.”

“For many of us, these [data are] was very reassuring,” she added.

Ultimately, the combined PROs from both the neoadjuvant and adjuvant phases support the use of pembrolizumab in this patient population, with pooled data across GHS, functional, and breast cancer symptoms domains confirming that pembrolizumab did not have a meaningful effect on HRQOL, Dent concluded.

Dent R, Cortés J, Pusztai L, et al. HRQoL with neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: results from KEYNOTE-522. Presented at: ESMO Congress 2022; September 9-13, 2022; Paris, France. Abstract 135MO.

Patients with triple-negative breast cancer who received pembrolizumab in the neoadjuvant and adjuvant settings demonstrated similar health-related quality-of-life scores compared with patients who received placebo. 

Breast Cancer