There may be a disconnect between oncologist’ perception of their prescribing patterns and their actual prescribing tendencies for genetic counseling and testing based on race, according to findings published in the 

Among 277 physicians surveyed, only 1.8% responded that they believed they were more likely to refer a White patient than refer a Black patient for genetic counseling and testing (GCT). A total of 66.9% of responders believed that Black women with breast cancer have lower rates of GCT than White women, although 63.4% acknowledged that Black women face more GCT barriers than White women do, and 21% agreed that Black women need more resources and guidance throughout the GCT decision-making process.

Overall, the majority of participants believed that lack of trust was a more significant barrier among Black women; 32% of physicians claimed that lack of trust was a barrier to GCT in all populations, while 58.1% stated that their barrier was felt more by Black women. Furthermore, 13.9% stated that noncompliance was an issue with all patients, while 30.6% felt that Black women are more likely than White women to be noncompliant to GCT recommendations (

“Physicians, being the gatekeepers of health care knowledge, have a direct impact on GCT rates in African American women with breast cancer. The role that inequitable physician referrals play in the observed racial inequities in the utilization of GCT for breast cancer has been partly elucidated,” wrote Foluso O. Ademuyiwa, MD, MPH, MSCI, Department of Medicine, Washington University School of Medicine, and colleagues in the study. “This nationwide survey will serve as a basis for understanding physicians’ determinates of GCT for African American women and highlights the necessity of education and interventions to address bias among physicians. Awareness of such inequities can enable further work to address inequities, ultimately leading to improved GCT equity for African American women with breast cancer.”

The study reminded readers that the age-adjusted US mortality rate per 100,000 for breast cancer is 28.7 in Black women vs 20.3 in White women. These statistics represent a 41% increased mortality rate for African American women. A higher percentage of biologically aggressive tumors, as well as limited scientific understanding of the genetic risk factors within this patient population, are both factors that have continued to this disparity in cancer care.

Moreover, although genetic testing has revealed that Black women and White women carry similar rates of pathogenic variants, White women are almost 5 times more likely to receive GCT than Black women.

The survey participants were 58.8% female. Seventy-five percent were medical oncologists and 61.7% were academic physicians. Overall, 67.1% were White, 23.8% were Pacific Islander, and 3.3% were Black. The survey included 49 items and queried participants about their own demographics, clinical characteristics, knowledge, attitudes, practices, and perceived barriers in referring patients with breast cancer for GCT.

Although 97.1% of participants demonstrated thorough knowledge of HBOC genetics, only 73% had a thorough understanding of the Genetic Information Nondiscrimination Act. Similarly, despite the fact that 94.2% of respondents stated that they properly understood NCCN guidelines for HBOC testing, 55.1% stated that the NCCN guidelines were complicated. Furthermore, although more than half of respondents claimed the guidelines are complicated, 94.2% still believed they were qualified to recommend GCT to their patients in clinical practice.

Only 5 people who responded to the survey thought they were more likely to refer a White patient for GCT than an African American patient.

Furthermore, only 37.7% of respondents expressed that all patients with breast cancer should undergo GCT while a significant portion (82.2%) stated that all patients with breast cancer should obtain testing only after counseling. A smaller percentage (73.8%) stated that all Black patients with breast cancer should obtain testing only after counseling.

A portion of participating oncologists shared that a consideration of the psychologic distress connected to GCT also influenced their referring decisions. According to the results, 51.6% of oncologists believe that patient distress increased if patients received genetic testing and 54.8% of oncologists believed that Black patients with breast cancer are more likely to experience an increase in psychological distress, compared with White patients. In contrast, only 32% believed that a patients’ lack of trust is a barrier to GCT for all patients with breast cancer, whereas 58.1% of oncologists felt that this barrier is more significant among Black women with breast cancer.

Researchers also assessed the oncologist’s perception of patient’s insurance and potential job discrimination. Fifty-eight percent of oncologists felt that poor insurance or job discrimination related to having a pathogenic mutation was more common among Black patients. Findings also demonstrated that 25.7% of oncologists believe that Black women are more likely to refuse to undergo GCT compared to White women.

The majority of participants (64.1%) agreed that GCT costs were a barrier for all patients, however, nearly half felt that this cost was more of a barrier among Black women (46%).

In summarizing the main findings, the study authors addressed the significance of perceived complicated NCCN testing guidelines. Racial inequities may potentially be exacerbated if complicated guidelines are being used in busy oncology clinics, they wrote. Furthermore, the study authors noted that a high percentage of oncologists believe that Black women have more GCT-related barriers than White women, believing that lack of trust and poor compliance records were more common among this population.

The study also highlighted a disconnect between physicians’ self-reported attitudes and actual practicing habits. Although studies have demonstrated that Black patients receive significantly lower GCT referral rates, merely 2% of oncologists believe that they are more likely to refer a White patient.

“There were no observed racial differences in self-reported practices regarding recommending referrals for GCT or actually obtaining testing,” concluded the study authors. “In previous studies, we and others have shown that African Americans who meet NCCN criteria are much less likely than Whites to be referred for or undergo GCT. It is possible that physicians may not recognize that they are inadvertently contributing to racial inequities. This underscores the need for programs to enhance awareness among oncologists to enable effective and guideline-concordant GCT for African Americans.”

“In this personalized medicine era, the knowledge of a patient’s germline genetic status can lead to improved clinical management, cascade family testing, and prevention of other malignancies in patients and their relatives,” they added. “Therefore, achieving appropriate use of GCT in African American patients is an essential step in minimizing on- going and future racial disparities in clinical outcomes.”

Foluso OA, Salyer P, Tao Y, et al. Genetic counseling and testing in African American patients with breast cancer: a nationwide survey of US breast oncologists. 2021; doi: 10.1200/JCO.21.01426 

Articles

Although White women and Black women carry similar rates of pathogenic variants, a study found that White women were almost 5 times more likely to undergo genetic counseling and testing.

Oncologist Attitudes May Factor into Underutilization of Genetic Counseling, Testing in Black Women with Breast Cancer

The ESMO Clinical Practice Guidelines for metastatic breast cancer, published in the 

 state that disease management should be nuanced and multidisciplinary across all subtypes in order to improve personalize locoregional, systemic, and supportive care.

“The rapid pace at which scientific knowledge is currently advancing means that new evidence may emerge between the time at which documents like the ESMO Clinical Practice Guidelines are developed and their eventual publication and use by clinicians,” Giuseppe Curigliano, MD, PhD, an associate professor of medical oncology at the University of Milano, head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, in Italy, and chair of the ESMO Guidelines Committee, said in a news release.

“The up-to-date guideline on metastatic breast cancer was therefore designed to integrate even the most recent, potentially practice-changing data by providing graded recommendations for different treatment choices according to the levels of evidence available to support them, based on their rating within the ESMO Magnitude of Clinical Benefit Scale and the ESMO Scale for the Clinical Actionability of Molecular Targets,” Curigliano added.

Although survival outcomes have improved for patients with metastatic breast cancer, 5-year survival rates remain around 38%.

 Therefore, optimization of available therapies is needed to maintain and further improve outcomes for patients. As such, establishing international guidelines could help to standardize treatment options and outcomes across the world.

The guidelines include a proposed diagnostic work-up and staging flow chart. It states that all patients with newly diagnosed or current metastatic breast cancer should have a biopsy of their metastatic lesion to confirm histology and reassess biomarker status, such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Additionally, tumor heterogeneity should be considered for each new line of treatment.

Other therapeutically relevant biomarkers should be routinely tested for, including germline 

 mutations in HER2-negative metastatic breast cancer, PD-L1 status in triple-negative breast cancer (TNBC), and 

 mutations in ER/PR-positive, HER2-negative metastatic disease. Genomic profiling by tumor tissue or circulating tumor DNA should be performed when results could change treatment selection.

Imaging for staging and risk assessment should incorporate at least a CT scan of the chest and abdomen and a bone scintigraphy. Treatment should be initiated no more than 4 weeks after imaging and response evaluation should occur every 2 to 4 months.

Additionally, brain imaging should not be routinely performed for all asymptomatic patients at diagnosis or during disease monitoring; however, subtype-oriented brain imaging can be considered if the presence of central nervous system metastases will alter treatment decisions for patients with HER2-positive breast cancer or TNBC that have a higher rate of brain metastases. Symptomatic patients should always undergo brain imaging.

Patients with ER-positive, HER2-negative metastatic breast cancer should receive estrogen therapy with an aromatase inhibitor or fulvestrant (Faslodex) plus a CDK4/6 inhibitor in the frontline setting. In patients for whom organ failure is imminent, chemotherapy followed by maintenance or next-line endocrine therapy plus a CDK4/6 inhibitor should be considered.

Upon progression, patients without a risk of organ failure are eligible for fulvestrant plus a CDK4/6 inhibitor if not previously used, everolimus/exemestane or everolimus/fulvestrant, fulvestrant/alpelisib (Piqray) if 

 mutated. Chemotherapy should be given upon progression after several lines of endocrine therapy with or without targeted therapies.

In the first-line setting, patients with hormone receptor (HR)–positive, HER2-positive disease with chemotherapy contraindications should receive trastuzumab (Herceptin) with or without pertuzumab (Perjeta) and endocrine therapy. Patients with HR-negative, HER2-positive disease with chemotherapy contraindications should receive trastuzumab/pertuzumab. Regardless of HR status, patients without chemotherapy contraindications should receive docetaxel or paclitaxel, trastuzumab, and pertuzumab followed by trastuzumab, pertuzumab, and endocrine therapy.

Second-line treatment for patients with active brain metastases for whom local intervention is indicated are eligible for resection with or without stereotactic radiotherapy or whole-beam radiation therapy based on the number of active brain metastases. In patients for whom local intervention is not indicated or for those without active brain metastases, tucatinib (Tukysa)/capecitabine/trastuzumab or fam-trastuzumab deruxtecan-nxki (Enhertu) is indicated. Third-line and beyond treatment recommendations are the same for patients with active brain metastases; however, in patients without active brain metastases, ado-trastuzumab emtansine (T-DM1; Kadcyla) can be considered in the third-line setting, followed by lapatinib (Tykerb)/trastuzumab, trastuzumab/chemotherapy, margetuximab (Margenza)/chemotherapy, or neratinib (Nerlynx)/chemotherapy in subsequent lines of therapy.

Patients with PD-L1–positive TNBC should receive atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) or pembrolizumab (Keytruda) plus chemotherapy. Patients with 

-mutated TNBC should receive chemotherapy- or PARP inhibitor–based treatment. Patients with PD-L1–negative, 

 wild-type TNBC should receive anthracycline/taxane–based therapy, taxane/bevacizumab (Avastin), or capecitabine/bevacizumab if organ failure is imminent, or taxane or anthracycline monotherapy if organ failure is not imminent.

Upon progression, sacituzumab govitecan-hziy (Trodelvy) or chemotherapy is indicated for all patients followed by chemotherapy with eribulin (Halaven), capecitabine, or vinorelbine.

Hereditary Breast Cancer and Oligometastatic Disease

Patients with HER2-negative metastatic breast cancer who harbor germline pathogenic or likely pathogenic variants in 

 should be considered for PARP inhibitor therapy with olaparib (Lynparza) or talazoparib (Talzenna) irrespective of HR status.

In patients for whom oligometastatic disease is confirmed, a multidisciplinary team should consider the site of metastases, management of primary tumor and axilla, systemic treatment options, and localized approaches when making treatment decisions for patients.

Supportive and Palliative Care Recommendations

In all cases of metastatic breast cancer, multidisciplinary care should be utilized. Moreover, specialized oncology or breast care nurses should proactively screen patients for treatment-emergent toxicities, which should be managed accordingly. Quality-of-life assessments should be incorporated into the evaluation of treatment efficacy, and dose reductions or delays should be utilized in cases of toxicity.

It is important to incorporate palliative care early in inpatient and outpatient settings. With the rising median overall survival in metastatic breast cancer, patients are more likely to develop metastases in several areas of the body. As such, optimal symptom control, as well as psychological, social, and spiritual support should be implemented after patients receive best available therapy.

Shared-decision making between the provider and patient/family should be utilized to educate, establish goals and expectations, and optimize care.

Finally, health care professionals should have mental health support available to them to ensure they are able to provide sensitive and effective care to patients.

Gennari A, André F, Barrios CH, et al. ESMO clinical practice guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer. 

. Published October 13, 2021. Accessed November 2, 2021. doi:10.1016/j.annonc.2021.09.019

Metastatic breast cancer: new ESMO guideline with evidence-based recommendations [ESMO press release]. News release. ESMO. October 19, 2021. Accessed November 2, 2021. 

This article was originally published on OncLiver as “ESMO Guidelines Recommend Personalized Treatment and Multidisciplinary Decision Making in Breast Cancer

Nuanced and multidisciplinary decision making are needed to optimize and personalize locoregional, systemic, and supportive care in metastatic breast cancer. 

New ESMO Breast Cancer Guidelines Emphasize Personalized Treatment, Multidisciplinary Decision Making

Oncology nurses may help patients improve quality of life (QOL) by implementing the Oncology Nursing Society (ONS)’s new Get Up, Get Moving Program into treatment plans, findings demonstrated from a pilot study published in the 

In addition, the findings suggested that nurses who discuss physical activity with patients at their first visits, including physical activity in the treatment plan and planned weekly telephone calls from nurses, can help encourage and sustain patient activity.

The study found that patients who received nurse intervention had significantly increased exercise levels by the conclusion of the 12-week program. Although both groups started with similar mean scores in the Godin-Shephard Leisure-Time Physical Activity Questionnaire (34.75 and 31.11, respectively), the experimental group had a mean score of 48.67 (SD = 23.29; t = –3.555; degrees of freedom [df] = 8; 

 = .007) at the end of the program, compared with a mean of 29.25 (SD = 18.6; t = 0.754; df = 7; 

 = .47) among patients who did not receive intervention.

“This 12-week pilot study illustrates that the ONS Get Up, Get Moving Program, coupled with weekly nurse telephone calls, is 1 example of a low-cost, easy-to-implement, nurse-led intervention to possibly mitigate health-related QOL declines and increase activity level outcomes of patients with cancer,” wrote Judi K. Forner, DNP, APRN, ACNS-BC, RN-BC, OSF HealthCare Cardiovascular Institute, and colleagues. “Traditionally, oncology nurses recognize and treat therapy-related symptoms. However, they are also pivotal in supporting physical activity and other positive behaviors through therapeutic communication.”

The randomized pilot study assessed a total of 17 patients at a Midwestern hospital-based outpatient infusion center and took place between November 2019 and August 2020. To be eligible, patients needed a stage I to II solid tumor breast cancer or prostate cancer diagnosis or a stage I to III colon cancer diagnosis.The age of participants ranged from 30 to 80 years of age, and at the time of the study, all patients were being treated with either chemotherapy, radiation, or a combination of the 2.

All of the participants received a Fitbit Inspire activity tracker and select materials related to the study. The 8 members of the control group continued standard care while the 9 members in the intervention group received weekly telephone coaching phone calls from a clinical nurse specialist. The Get Up, get Moving Intervention Program lasted 12 weeks, although admission was staggered to align with patient consent.

Both groups reported their daily step count on weeks 1 and 12, however, the intervention group also reported their daily steps each week throughout the program. Initially, the step counts were similar between the 2 groups (intervention group, 6,337 steps vs control group, 6,169 steps). By the conclusion of the program, the intervention group was reporting significantly more daily steps than the control groups (8,047 steps vs 4,478 steps, respectively). The step counts combined with the Godin Scale Scores showed that intervention with the program resulted in increased physical activity.

Furthermore, the study indicated that physical activity intervention may also help sustain QOL throughout cancer treatment. The group who received nurse intervention did not report changes in their self-reported, health-related QOL. In comparison, the control group reported both a decline in general health as well as a trend toward lower energy and fatigue.

“The ONS Get Up, Get Moving quality improvement initiative provides evidence-based tools that oncology nurses can use to implement the program at their own cancer center. As the research has supported, low-impact exercise, even as simple as walking, can possibly decrease cancer treatment symptoms of fatigue and nausea while helping to maintain their quality of life,” Forner said in a press release. “We owe it to our patients to encourage physical activity during cancer treatment.”

Researchers noted that their investigation was hindered by the spread of the COVID-19 pandemic, since stay-at-home orders and mandates resulted in recruitment and physical activity transitioning to online and that exercise regimes were modified to comply with closed facilities and stay-at-home orders. Despite this, the study was able to continue in a modified fashion because the nurse intervention involved remote weekly telephone calls.

“This illustrates that a low-cost intervention using nurse-driven telephone calls and activity trackers could increase physical activity; the findings can add to best practice guidelines showing that regular physical activity can mitigate some of the psychological and physiologic effects of cancer treatment at relatively little cost,” the study authors wrote.

Study limitations included small sample size and short study time duration. The study authors concluded that future research should seek to understand the relationship between physical activity and health-related QOL among a larger sample of participants and different cancer types and treatments. Additionally, they added, redesigning the study is needed to assess intervention longer than 12 weeks, which may provide more specific insight into how the program affects long-term QOL.

Forner JK, Doughty A, Dalstrom MD, Messer BL, Lizer SK. A nurse-led physical activity coaching program to improve the quality of life of patients with cancer during the COVID-19 pandemic. October 2021. Accessed October 18, 2021. 

2021;25(5) 571-577. 10.1188/21.CJON.571-577

The implementation of the Oncology Nursing Society’s new Get Up, Get Moving Program helped patients increase their daily step intake and maintain their health-related quality of life. 

Nurse Intervention Helps Patients Maintain Physical Activity, Quality of Life During Cancer Treatment

Investigators participating in the phase 2 ACE-Breast03 trial (NCT04829604) aim to determine whether the novel antibody-drug conjugate (ADC), ARX788, represents a safe and effective treatment option for patient with metastatic HER2-positive breast cancer whose disease has progressed beyond other HER2-directed therapies, according to a news release from Keck Medicine of the University of Southern California (USC).

The global registration study is currently enrolling patients who experienced resistance to or disease progression on regimens containing ado-trastuzumab emtansine (T-DM1; Kadcyla), fam-trastuzumab deruxtecan-nxki (Enhertu), and/or tucatinib (Tukysa).

“At USC Norris [Comprehensive Cancer Center], we treat a large volume of patients with HER2-positive, metastatic breast cancer and we have found that resistance to existing therapies is a major issue,” said global lead principal investigator Janice Lu, MD, PhD, a medical oncologist with Keck Medicine and medical director of the USC Comprehensive Breast Oncology Program, in the news release.1 “We are excited to lead this effort in assessing a possible alternative solution for breast cancer patients and hope to expand our ability to provide effective personalized care.”

ARX788 is an ADC that combines a HER2-directed monoclonal antibody with Amberstatin269, which can destroy cancer cells and prevent new cell growth.

Prior findings from phase 1 trials demonstrated encouraging antitumor activity with ARX788 in patients with HER2-overexpressing solid tumors.2 The overall response rate (ORR) was 74% with 1.5 mg/kg of ARX788 in patients with HER2-positive breast cancer and 67% in patients with HER2-overexpressing solid tumors. Across both populations, the disease control rate (DCR) was 100%.

In the phase 2 trial, patients will receive an intravenous infusion of ARX788 every 4 weeks.3 Two hundred patients are estimated to enroll.

The primary end point of the study is ORR by RECIST v1.1 criteria over 2 years; secondary end points include duration of response, best percent change in the sum of the longest diameters of measurable tumors, best overall response, DCR, progression-free survival, overall survival, number of patients experiencing treatment-emergent adverse effects, maximum serum concentration for ARX788, total antibody, and pAF-AS269, trough concentration for ARX788, total antibody, and pAF-AS269, area under the serum concentration-time curve for ARX788, total antibody, and pAF-AS269, and incidence of anti-drug antibodies following administration of ADX788.

Eligible patients must be 18 years of age or older with a life expectancy of at least 3 months, an ECOG performance status of 1 or lower, and adequate organ function. Patients must have at least 1 measurable lesion per RECIST v1.1 criteria and adequate tumor samples available for HER2 status confirmation. Patients with stable brain metastases are eligible for enrollment.

Patients with a history of interstitial lung disease, pneumonitis, or other clinically significant lung diseases within 12 months of enrollment, ocular events or active ocular infections, or congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia within 12 months of enrollment are not eligible for the study.

Currently, patients are being recruited from over 20 sites in the United States and Australia. An additional 150 sites are planned to open worldwide, including Europe and Asia.1

Additionally, the trial will be presented during the 2021 San Antonio Breast Cancer Symposium as an ongoing trial.

“If this drug is effective, it could provide a hopeful alternative to patients with a difficult prognosis and help them maintain a quality of life in ways that chemotherapy cannot,” Lu concluded.

USC Norris Comprehensive Cancer Center launches global clinical trial testing potential therapy for aggressive type of breast cancer. News release. Keck Medicine of USC. October 11, 2021. Accessed October 14, 2021. 

Hurvitz SA, Park H, Frentzas S, et al. Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: results from two phase 1 clinical trials. 

. 2021;39(suppl 15):1038. doi:10.1200/JCO.2021.39.15_suppl.1038

ARX788 in HER2-positive, metastatic breast cancer subjects (ACE-Breast-03) (ACE-Breast03). ClinicalTrials.gov. Updated October 6, 2021. Accessed October 14, 2021. 

https://clinicaltrials.gov/ct2/show/NCT04829604

This article was originally published on OncLive as “Trial Launches to Evaluate Novel ADC in Previously Treated HER2+ Breast Cancer”

The recently launched phase 2 ACE-Breast03 seeks to appraise the efficacy and safety of the novel antibody-drug conjugate, ARX788, in patients with metastatic HER2-positive breast cancer whose disease is resistant to previous targeted therapies.

New Clinical Trial Will Assess Novel ADC in Drug Resistant HER2+ Breast Cancer

Coordination between oncology and primary care teams to care for underinsured and uninsured cancer survivors remains a challenge, suggested a new study published in 

Investigators interviewed 93 health care providers in a qualitative study and asked them to describe opportunities and challenges to coordinate care between oncology and primary care teams. The study defined survivors as patients with a stage I, II, or II diagnosis, who have completed cancer treatment (including chemotherapy, radiation, and/or surgery) and who have initiated the surveillance stage of their cancer care journey.

Key challenges included difficulties accessing primary care providers (PCPs), a lack of communication between oncology and primary care teams, role delineation from both sides of the care continuum, and a lack of clinician knowledge and preparedness.

“These findings suggest that, given interdependencies between levels within a single health system, awareness and engagement by system leadership may be needed to create the conditions necessary to actualize and sustain communication across teams to support comprehensive cancer survivorship care,” wrote Bijal A. Balasubramanian, MBBS, PhD, and colleagues, in the paper. “One immediate target is closed-loop communication, ensuring both vertical and horizontal communication pathways. Health information technology tools may also foster team effectiveness by better identifying high-risk patients, monitoring outcomes, and managing task interdependence during transitions in care.”

Difficulty accessing primary care was 1 of the most common problems reported by patients, particularly for those without a preexisting PCP. Although oncology nurses routinely referred patients with chronic conditions such as diabetes and hypertension to primary care, many patients faced wait times longer than 6 months before being seen.

Communication was another critical issue that concerned both oncology teams and PCPs. Investigators noted that oncology teams often expect the patient to communicate treatment symptoms to their PCP; however, because patient’s communication with PCPs are often less frequent and/or regular than their communication with their oncology team, and because cancer therapies can worsen preexisting chronic conditions, substantial consequences are a potential concern.

The lack of communication often translated into role delineation for cancer surveillance testing. For example, in the case of mammograms for survivors of breast cancers, both groups agreed that the oncology care team should manage surveillance for the first 5 years, however, they disagreed on who should manage surveillance for survivors of 10 years or more.

“Who is supposed to follow that cancer follow-up frequency? Is Oncology [going to] do it or primary care has to do it?” remarked one PCP in the study. “So, if they can put ‘We continue to follow’ [in the EMR], or if the patient is discharged from oncology and primary care has to follow up or whatever, then make that really more clear.”

“The ideal thing would be a survivorship program to see all survivors, at all stages. But [the Medical Oncology Clinic] doesn’t have the bandwidth to take all survivors now,” added an oncology clinician.

Some PCPs felt that it would be better for the oncology care team to maintain surveillance because it is common for patients to fall out of their primary care routine. One PCP even expressed that “Cancer is not like any other disease. We really have to be very careful. If you leave [cancer surveillance] with the PCP … [patients] might not show up ... I don’t want patients to fall through the cracks.”

Furthermore, a number of PCPs expressed that they felt uncomfortable managing cancer-related pain and prescribing medications to help manage long-term treatment-related adverse events (AEs). Many PCPs shared that they were unfamiliar with the AEs their patients were experiencing and the prescriptions commonly used to treat them.

“I have a patient with [brain metastases]…and he was started on 3 seizure medications, and he doesn’t have seizures but I guess they have a role in treating headaches. He’s on 3 medications that I am not familiar with. The last 3 [or] 4 months, the medication refill comes to me ... I am uncomfortable with these 3 medications. I don’t prescribe 3 seizure medications to treat a headache,” said a PCP.

“Care coordination for underinsured and uninsured cancer survivors with comorbidities will continue to be an important issue given changing US demographics, early detection, and advances in cancer therapies that have extended cancer survivorship,” concluded the study authors. “Without robust communication systems and care pathways between primary care and oncology, such patients are at risk of increasingly poor outcomes, exacerbated by the patchwork nature of the US health care system. Closed-loop communication, role clarification, leadership support, and health information technology improvements to comanage patients during care transitions may provide a start toward enhanced team-based care.”

One notable limitation was that investigators spoke to providers whose patients sought oncology and primary clinics that were owned and operated under the same governance. The authors acknowledged that patients who seek specialty care independent of their primary care might face more severe access barriers. Future research should seek to assess how to better facilitate communication across external oncology practice partners, in addition to clinics operating under the same governance as the PCP.

Balasubramanian BA, Higashi RT, Rodriguez SA, Sadeghi N, Santini NO, Lee SC. Thematic analysis of challenges of care coordination for underinsured and uninsured cancer survivors with chronic conditions. 

 2021;4(8):e2119080. doi:10.1001/jamanetworkopen.2021.19080

A recent study identified some of the key challenges in coordinated care for underinsured and uninsured cancer survivors who have initiated the surveillance stage of their journey.

Stronger Coordination with PCP a Necessity in Caring for Cancer Survivors  

The FDA has approved abemaciclib (Verzenio) as an adjuvant therapy in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) to treat hormone receptor (HR)-positive, human epidermal growth factor receptor2 (HER2)-negative, node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test, according to a press release issued by Eli Lilly and Company.

"Women and men living with high-risk HR-positive, HER2-negative early breast cancer want to do all they can to reduce the risk of the disease coming back, with the hope of living free of cancer. The approval of [abemaciclib] provides a new treatment option to help them do just that," said Jean Sachs, chief executive officer, Living Beyond Breast Cancer, in the release. "This approval brings new optimism to the breast cancer community."

The regulatory decision is based on findings from the randomized, open-label, 2-cohort, multicenter, phase 3 monarchE trial, designed to evaluate abemaciclib plus standard endocrine therapy versus standard endocrine therapy alone in adult patients with HR-positive, HER2-negative, node-positive, resected EBC with clinical and pathological features consistent with a high risk of disease recurrence. Patients were treated with either 2 years of abemaciclib 150 mg twice daily plus standard endocrine therapy, or with standard endocrine therapy as a monotherapy. Patients in both cohorts were prescribed adjuvant endocrine therapy for 5 to 10 years.

The primary end point was invasive disease-free survival (IDFS), defined as the length of time before the breast cancer returns, new cancer develops, or death, and has already been met a pre-specified interim analysis in the intent-to-treat population. Patients receiving abemaciclib have demonstrated superior IDFS compared with those treated with endocrine therapy as a monotherapy.

Overall survival data is not yet ready for analysis and investigators are continuing to conduct additional follow-ups.

No new safety signals were detected in the monarchE trial. Safety and tolerability were assessed across 5,591 patients, of which the most common adverse events (AEs) were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, dizziness, rash, and alopecia.

Laboratory abnormalities to monitor for include an increase in creatinine, a decreased white blood cell count, decreased neutrophil count, anemia, lymphocyte count, platelet count, increased ALT, increased AST, and hypokalemia.

Patients should receive blood counts and liver function tests prior to initiating treatment with abemaciclib. These tests should continue every 2 weeks for the first 2 months, monthly for the following 2 months, and so on, as clinically indicated. Patients taking this medication will also require monitoring for thrombosis and pulmonary embolism.

Patients should be taught to immediately initiate antidiarrheal therapy, increase oral fluids, and notify their health care providers at the first sign of loose stools. The labelling for the drug includes precautions for diarrhea, neutropenia, interstitial lung disease hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity.

In addition, patients should understand that this drug poses serious risk to a fetus. The label urges patients to plan accordingly by using effective contraception.

"The design and results of the monarchE study are practice-changing and represent the first advancement in adjuvant treatment of HR-positive, HER2-negative breast cancer in a very long time," said Sara M. Tolaney, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute, and investigator on the monarchE study. "This FDA approval for Verzenio in combination with endocrine therapy in the early breast cancer setting has the potential to become a new standard of care for this population. We are encouraged by the marked reduction in the risk of recurrence even beyond the two-year treatment period in these patients, and I'm grateful to be able to offer this as a treatment option to my patients."

Eli Lilly and Company News Release. FDA approves Verzenio® (abemaciclib) as the first and only CDK4/6 inhibitor for certain people with HR+ HER2- high risk early breast cancer. Lilly. Published October 13, 2021. 

https://investor.lilly.com/news-releases/news-release-details/fda-approves-verzenior-abemaciclib-first-and-only-cdk46.

Abemaciclib is the first and only FDA approved CDK4/6 inhibitor to treat HR-positive, HER2-negative high-risk early breast cancer.

FDA Approves Abemaciclib for HR+, HER2– High-Risk Early Breast Cancer

indicate that 6 months following the second dose of the Pfizer-BioNTech COVID-19 vaccine, patients with solid tumors and individuals without cancer displayed similar levels of COVID-19 antibodies in their blood.

Results from the study showed that 79% of those with solid tumors were seropositive for the antibodies compared with 84% of healthy controls at 6 months after their second dose of the vaccine. However, antibody levels in both groups decreased significantly from the time of vaccination.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” said lead study author Irit Ben-Aharon, MD, PhD, director of the oncology division at Rambam Health Care Campus in Israel.

Though the available COVID-19 vaccines have shown high efficacy in the general population, their long-term safety and efficacy among patients with cancer had been underrepresented. Moreover, patients with cancer receiving cytotoxic therapy or immune modifying agents were not able to participate in other vaccine studies, and as such, there remains an unmet need to examine the efficacy of the vaccines in this group.

Although it had been suggested that all patients with cancer were at increased risk for COVID-19 infection, recent studies have shown that outcomes and manifestations differ significantly depending on the malignancy type and treatment. Furthermore, data on vaccine efficacy in patients with cancer have shown similar short-term efficacy and safety among patients with when compared with healthy controls.

In this study, investigators sought to examine the long-term safety and efficacy of the COVID-19 vaccine in this population at 6 months after vaccination.

The study enrolled patients with solid tumors receiving active anti-cancer therapy and followed their progress for 6 months after the administration of the second dose of the vaccine. Patients must have been receiving their cancer therapy throughout 6-month duration, as well.

In the study cohort overall, investigators enrolled 154 patients with solid tumors, in addition to 135 age-matched healthy controls. Of the original cohort, 88 patients were enrolled; 64 who met the inclusion criteria were subsequently added.

In the solid tumor cohort, the median age was 66 years (range, 32-87), and more than half of patients were male (55%). In the control cohort, 56% of individuals were women and the median age was 63 years old (range, 50-87).

Most of the patients with cancer enrolled presented with metastatic disease (84%), and the most common cancer types were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary cancers (11%). Moreover, the most common anti-cancer treatment among patients was chemotherapy (62%), followed by biological agents (36%) and immunotherapy (30%).

Additional data showed that chemotherapy was more highly associated with seronegative serologic status vs other treatment modalities (27% vs 10%; odds ratio [OR], 0.31; 

 = .02), and women were more likely to be seropositive than men (93% vs 75%; OR, 0.21; 

Furthermore, there was 1 documented case of severe COVID-19 infection that required hospitalization in the cohort of patients with cancer.

In terms of safety, elevation of liver enzyme levels was reported in 10% of patients with cancer up to 6 weeks after receiving the first dose of the vaccine. Moreover, newly documented regional lymphadenopathy was reported on 5% of CT/PET scans. However, all adverse effects were resolved in all patients throughout the course of the study period.

Additionally, the vaccination led to anti-cancer treatment delays for 6% of patients with cancer, all of whom were receiving chemotherapy. Delays were most commonly due to neutropenia, mild thrombocytopenia, and neutropenia with herpes labialis.

“Our study indicates that the pattern of immunogenicity and efficacy of the [Pfizer-BioNTech COVID-19 vaccine] in patients with solid tumors on active intravenous anti-cancer treatment 6-months post vaccination resemble the pattern of the general population,” the study authors concluded. “Former subtle differences which were evident between the 2 cohorts shortly after vaccination disappeared throughout time. Nonetheless, due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal.”

Waldhorn I, Holland R, Goshen-Lago T, et al. Six month efficacy and toxicity profile of BNT162b2 vaccine in cancer patients with solid tumors. 

. Published online September 2, 2021. doi:10.1158/2159-8290.CD-21-1072

Six-month efficacy of Pfizer/BioNTech COVID-19 vaccine in patients with solid tumors similar to general population. News release. American Association for Cancer Research. September 2, 2021. Accessed September 2, 2021.

The Pfizer-BioNTech COVID-19 vaccine induces similar levels of COVID-19 antibodies in patients with solid cancer compared with people without cancer.



COVID-19 Vaccine Elicits Similar 6-Month Antibody Response in Both Patients with Solid Tumors and the General Population

Particularly for women, breast cancer remains the highest cancer with an estimated 281,550 new cases in 2021 alone. While the survival rates for breast cancer have overall improved due to advancements in treatment and clinical trials, Black, Indigenous, People of Color (BIPOC) still represent the population with the highest death rates among all demographics.

BIPOC patients diagnosed with breast cancer often face additional barriers–like health disparities, health literacy, and lack of knowledge of the psychosocial effects–in comparison to other ethnic groups. Such barriers are not often addressed in a medical setting, which can contribute to BIPOC’s mortality rate and poorer outcomes.

Not only do BIPOC have a higher mortality rate in comparison to their White counterparts, they are also more likely to be diagnosed at a younger age, and at a more advanced and/or aggressive stage. There are many reasons for this.

One factor is due to the lack of access to resources, which can prevent BIPOC individuals from having their cancer detected early, receiving quality care, or experiencing a delay in their treatment. BIPOC’s limited access to care is common within low income, predominantly BIPOC neighborhoods as well.

Furthermore, it has been documented BIPOC are not effectively represented in studies in various treatment options for breast cancer, especially in clinical trials. This is essential as the genetic makeup of tumors in BIPOC can differ in comparison to other ethnicities, including triple-negative breast cancer.

So, while advancements in treatment among the White population have shown to be successful, less is known about how the same or similar treatments would positively impact BIPOC, including whether other remedies are needed.

Difficulties with understanding cancer treatment and medical terms are common among all patients with cancer. However, it is even more evident among BIPOC due to various social-economic factors, such as educational background. Specifically, with patients with breast cancer, BIPOC reported they received limited information about their treatment side effects, including infertility.

BIPOC patients further expressed not feeling comfortable asking questions with their medical team as they are answered in terms they do not comprehend. Lack of clear communication can additionally make BIPOC distrustful of their medical teams, which then results in them seeking information that might be inappropriate or incorrect elsewhere. Additionally, patients who feel they do comprehend their treatment can feel overwhelmed, and then are not able to make informed decisions.

Lastly, BIPOC patients are often not educated on alternative treatment options including clinical trials. As a consequence, BIPOC may be resistant to medication/treatment compliance or lack the willingness to participate in studies that can assist with advancements in treatments among the BIPOC community.

People diagnosed with breast cancer experience similar psychosocial effects as others with cancer, including depression and anxiety. However, in the BIPOC population, such effects are often ignored.

In a study conducted by Lewis et al, they found that BIPOC’s depression are “often under-recognized and under-treated.” They further noted how such acknowledgements would make an impact in a BIPOC’s cancer journey and quality of life.

Such studies highlight the lack of emotional support services BIPOC receive during their treatment, including providing them with the tools to help them navigate through their cancer experience. Often, there are misconceptions about how BIPOC cope with cancer. This can impact how BIPOC patients cope with their diagnosis, including limiting their access to resources such as counseling or support groups, and their willingness to participate with follow-up after treatments.

If BIPOC patients find their cancer experience traumatic, it may make them reluctant to engage in follow-up, which is significant to prevent and minimize a reoccurrence.

There are ways medical professionals can begin to help BIPOC patients with breast cancer navigate through their cancer journey as well as cope with the challenges they endure:

Listen: It makes a difference when BIPOC feel they are being heard and validated by their medical team. There are numerous stories within the BIPOC communities of how often providers dismissed their feelings when they expressed their concerns, especially feelings such as hopelessness depression or their experience with side effects.

Educate: Providing an environment for open-ended questioning and not rushing a patient during appointment can help a BIPOC develop an overall better understanding of their diagnosis and their options. They are then able to make a more educated and informed decision.

Understanding Certain Stereotypes:Sadly, there are stereotypes against BIPOC women that affect their care. These include being seen as very “strong “or “angry/aggressive.” Many do not understand how BIPOC’s appearance of strength or anger are rooted in having to adapt often to various struggles and disparities throughout the course of their lives. This appearance, sadly masks vulnerable feelings that providers fail to address. Be mindful when using certain words including telling a patient they are strong or brave. While such statements are intended to inspire hope, they can also dismiss someone’s feelings of depression. It is important to provide a place where patients feel comfortable with admitting they need help or support. There is a useful workshop series from Living Beyond Breast Cancer, which has some insight to BIPOC’s struggles with breast cancer for reference.

Familiarize yourself with available resources:This would include databases for clinical trials and psychosocial support such as support groups and counseling services as well as encouraging patients to utilize them. Also, be mindful not to immediately push them to see a social worker or financial navigator. Validate their feelings and hear their concerns to direct them to the appropriate resources.Some resources for support include CancerCare, Triple Negative Breast Cancer Foundation, Black Cancer, Touch, The Black Breast Cancer Alliance, and Susan G Komen Foundation.

The more people who are aware of BIPOC’s struggles with breast cancer, the more their barriers can be addressed. Decreasing such barriers can make a significant difference to increase the survival rates for BIPOC with breast cancer.

1. Cancer stat facts: cancer disparities. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer.gov/statfacts/html/disparities.html

2. Health Equity Initiative. https://www.komen.org/about-komen/our-impact/breast-cancer/health-equities-initiative/

3. Yedjou, Clement G et al. “Health and Racial Disparity in Breast Cancer.” Advances in experimental medicine and biology vol. 1152 (2019): 31-49. doi:10.1007/978-3-030-20301-6_3

4.Lewis, Pamela E et al. “Psychosocial concerns of young African American breast cancer survivors.” Journal of psychosocial oncology vol. 30,2 (2012): 168-84. doi:10.1080/07347332.2011.651259

5.Rust, Connie, and Cindy Davis. “Health Literacy and Medication Adherence in Underserved African-American Breast Cancer Survivors: A Qualitative Study.” Social work in health care 50.9 (2011): 739–761. Web.

6.Sheppard, Vanessa B et al. “Correlates of depressive symptomatology in African-American breast cancer patients.” Journal of cancer survivorship : research and practice vol. 7,3 (2013): 292-9. doi:10.1007/s11764-013-0273-y

BIPOC patients diagnosed with breast cancer often face additional barriers–like health disparities, health literacy, and lack of knowledge of the psychosocial effects–in comparison to other ethnic groups.

Barriers in BIPOC Populations Diagnosed With Breast Cancer

Patients with treatment-naïve triple-negative breast cancer (TNBC) responded well to carboplatin plus neoadjuvant paclitaxel followed by doxorubicin and cyclophosphamide, according to findings from the phase 3 BrighTNess trial (NCT02032277).

The 4-year follow-up, presented during the 2021 ESMO Congress, revealed significantly improved pathological complete response (pCR) rates and event-free survival (EFS) among participants.

Notably, the addition of veliparib to carboplatin had no impact on the primary endpoints.

At a median follow-up of 4.5 years, the addition of the PARP inhibitor veliparib to carboplatin and paclitaxel resulted in a 37% reduction in the risk of events or death compared with paclitaxel alone (HR, 0.63; 95% CI, 0.43-0.92; 

 = .02). However, when the veliparib regimen was compared with carboplatin/paclitaxel, no event-free survival (EFS) benefit was observed (HR, 1.12; 95% CI, 0.72-1.72; 

 = .62). Post-hoc analyses showed that EFS was most improved with carboplatin/paclitaxel compared with paclitaxel (HR, 0.57; 95% CI, 0.36-0.91; 

“Adding carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the pathologic complete response significantly, and this translated into an improved EFS by an absolute 11% after a median follow-up of 4.5 years,” Sibylle Loibl, MD, lead study author and chair of the German Breast Group in Germany, said in a virtual presentation on the findings. “The addition of veliparib did not impact pCR, EFS, or [overall survival]. These findings, overall, support the inclusion of carboplatin into neoadjuvant chemotherapy for stage II to III TNBC, regardless of germline 

TNBC is known to have the highest risk of recurrence and a worse overall prognosis for survival compared with other breast cancers. Standard treatment is comprised of neoadjuvant chemotherapy followed by surgery.

In the double-blind, placebo-controlled, phase 3 BrighTNess trial, 634 patients with treatment-naïve stage II/III TNBC were randomized 2:1:1 to receive paclitaxel at 80 mg/m2 weekly for 12 doses in up to 16 weeks plus carboplatin at area under the curve (AUC) 6 mg/mL every 3 weeks for 4 cycles plus veliparib at 50 mg orally twice daily (arm A; n = 316); carboplatin plus paclitaxel plus placebo (arm B; n = 160); or paclitaxel plus placebo (arm C; n = 158).

Doxorubicin was then given at a 60-mg/m2 dose with cyclophosphamide at 600 mg/m2 every 2 or 3 weeks for 4 cycles. Patients underwent surgery 2 to 8 weeks following the last dose of chemotherapy. A postsurgical assessment was done every 3 months until 1 year after surgery, followed by every 6 months until 2 years after surgery, and then annually until 4 years after surgery or until an EFS event.

To be eligible for enrollment, patients had to be at least 18 years old, have histologically or cytologically confirmed invasive stage II/III TNBC, have an ECOG performance status of 0 or 1, and be eligible for potentially curative surgery with documented germline 

Those who received prior anticancer therapy, had prior or concurrent cancer, or were on ovarian hormonal replacement therapy were excluded from study enrollment.

Patients were stratified based on germline 

 status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide administration.

The primary end point of the trial was pCR; secondary end points were EFS and OS using a fixed testing procedure that ordered arm A vs arm C; and then arm A vs arm B. Both coprimary end points had to be statistically significant to continue formally testing secondary end points, Loibl noted.

Efficacy evaluations were done in all randomized patients; safety was analyzed in those who received at least 1 dose. In the primary pCR analyses, arm A was found to be superior to arm C, but not to arm B.

Baseline characteristics were similar across all 3 arms. The median age was 50 years (range, 22-79), and 46.6% of patients were from North America compared with 38.6% from Europe and 15% from Asia-Pacific. Moreover, 14.6% of patients had deleterious germline 

 mutations; most patients (71.3%) had T2 stage tumors and 58% had N0 stage disease. Additionally, 55.3% of patients received doxorubicin/cyclophosphamide every 2 weeks. When breaking down patients by histological primary tumor grade, 59.6% had high grade, 20.3% had intermediate, 5.3% had low grade, and 14.3% of patients’ data were unknown/not reported.

Previously reported findings from the double-blind, placebo-controlled, phase 3 trial showed that the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the pCR rates in this patient population, but there was no benefit to adding veliparib to carboplatin and paclitaxel alone.

At that time point, the pCR rates were higher in the paclitaxel, carboplatin, and veliparib group, at 53% compared with 31% in patients who received paclitaxel alone (

 <.0001) but was not superior vs the patients who received carboplatin/paclitaxel at 58% (

However, the impact of neoadjuvant carboplatin on long-term outcomes remained uncertain, explained Loibl, who added that based on the primary analyses, the subsequent secondary analyses are descriptive with nominal 

At the 4.5-year median follow-up, additional results from a statistical analysis of OS showed that there were 38 deaths in arm A (12%), 16 in arm B (10%), and 22 deaths in arm C (14%). OS was not statistically significant different with the addition of veliparib to carboplatin/paclitaxel vs paclitaxel alone (HR, 0.82; 95% CI, 0.48-1.38; 

 = .45), but there was a trend for the carboplatin/paclitaxel (HR, 1.25; 95% CI, 0.70-2.24; 

 = .46). Carboplatin plus paclitaxel also showed a trend toward improved OS vs paclitaxel (HR, 0.63; 95% CI, 0.33-1.21; 

A 4-year follow-up of patients with treatment-naïve triple-negative breast cancer who received carboplatin plus neoadjuvant paclitaxel, followed by doxorubicin and cyclophosphamide, suggests that the regime induces superior pathological complete response and event-free survival.  

Breast Cancer