Loyda E. Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, an oncology nurse practitioner at the University of Wisconsin Carbone Cancer Center, provides an overview of the evolving treatment landscape in hormone receptor–positive breast cancer. Braithwaite highlights the emerging role of selective estrogen receptor degraders, selective estrogen receptor modulators, and updates on aromatase inhibitors within the space. She also discusses the management of potential treatment-emergent toxicities and how recently approved agents might make active treatment more accessible for certain patient populations.

“Decision-making doesn’t happen spontaneously,” Braithwaite says. “[There] are strong data and scientific research that show new therapies are emerging. It is up to us, as advanced providers, or as nurses, to make sure that we provide that education and that support [to our patients], because the evidence is out there.”

, please consider subscribing to our podcast on Apple Podcasts, Spotify, Google Podcasts, Amazon Music, and many of your other favorite podcast platforms, to get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

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Loyda E. Braithwaite, MSN, RN, AGPCNP-BC, AOCNP, highlights nursing considerations in prescribing and administering endocrine therapy to patients with HR+ breast cancer. 

Loyda Braithwaite Discusses Evolving Treatment Options in HR+ Breast Cancer 

Patients with breast cancer that harbors 

 fusions achieved deep and durable responses following treatment with entrectinib (Rozlytrek), according to updated data from the phase 2 STARTRK-2 trial (NCT02568267) presented at the ESMO Breast Cancer Congress 2022.

At a median duration of survival follow-up of 35.3 months in patients with 

 fusion–positive disease (n = 7), entrectinib elicited a 71% (95% CI, 29.0%–96.3%) overall response rate (ORR); 2 patients achieved a complete response (CR) and 3 patients had a partial response (PR). Response data were missing on the other 2 patients. Both patients who achieved a CR had secretory disease, and among the 3 patients to have a PR, 2 had secretory disease and 1 had non-secretory disease. Among the 5 responders, the median duration of response (DOR) was 12.9 months (95% CI, 4.2-not evaluable [NE]).

 gene fusions are drivers in many solid tumors, including breast cancer.

 Though less than 1% of all breast cancer cases harbor 

 fusions, they are present in more than 90% of secretory breast carcinomas.

Prior data from the ALKA-372-001 trial (EudraCT 2012-000148-88), the phase 1 STARTRK-1 trial (NCT02097810), and STARTRK-2 showed entrectinib demonstrated deep and durable responses in patients with 

 Prior data from STARTRK-2 showed patients with 

 fusion–positive breast cancer achieved an ORR of 83% (n = 5 of 6), a median DOR of 12.9 months (95% CI, 4.2-NE), a median progression-free survival (PFS) of 10.1 months (95% CI, 5.1-NE), and a median overall survival (OS) of 23.9 months (95% CI, 5.1-23.9).

STARTRK-2 enrolled patients with locally advanced or metastatic solid tumors that harbored an 

 fusion–positive breast cancer. Moreover, patients were eligible regardless of central nervous system (CNS) metastases, and patients were required to be naïve to TRK inhibitors.

Enrolled patients received 600 mg of entrectinib once daily. Tumor burden was assessed following the first cycle of therapy, followed by every 8 weeks after by blinded independent central review per RECIST v1.1 criteria. Notably, regular brain scans were required for patients with baseline CNS metastases.

The primary end points were ORR and DOR per blinded independent central review. Secondary end points included PFS, OS, intracranial efficacy, CNS progression, and safety.

 fusion–positive breast cancer, all were female with a median age of 61 years (range, 36-67), and 5 patients were White. Patients had an ECOG performance status of 0 (n = 3), 1 (n = 2), or 2 (n = 2). All patients had received prior chemotherapy, radiotherapy, and hormonal therapy, and 5 patients were administered prior targeted therapy. One patient had previous radiotherapy of the brain.

Prior lines of therapy for metastatic disease included 0 (n = 3), 1 (n = 1), 3 (n = 1), and 4 or more (n = 2). Two patients presented with CNS metastases at baseline, and the median time since diagnosis for all patients was 130.1 months (range, 32.6-309.1). Histology included non-secretory (n = 2), secretory (n = 4), and not specified (n = 1).

Additional data showed the median PFS was 10.1 months (95% CI, 5.1-NE), and the median OS was 19.2 months (95% CI, 5.1–NE).

In the 2 patients with CNS metastases at baseline, the first had HER2-positive, estrogen receptor (ER)–positive, PGR-negative disease and received whole brain radiation 2-6 months prior to beginning entrectinib. This patient received no prior lines of systemic therapy for metastatic disease, and she achieved a PR and an intracranial non-CR and non–progressive disease. The second patient had HER2-negative, ER-positive, PGR-positive disease and received 6 prior lines of systemic therapy for metastatic disease. This patient did not have response data after dying 1.7 months following the first dose of entrectinib, though her death was not considered related to treatment.

Notably, no patients experienced a CNS progression event, regardless of baseline status.

Among 12 patients who received at least 1 dose of entrectinib and were evaluable for safety, 4 patients experienced a grade 3 or higher treatment-related adverse effect (TRAE). These included anemia (n = 2), fatigue (n = 1), and increased alanine aminotransferase (n = 1). There were no grade 5 TRAEs recorded. Only 1 patient had a series TRAE.

The most common TRAEs of any grade included dizziness (n = 5), nausea (n = 5), anemia (n = 4), constipation (n = 4), vomiting (n = 4), dysgeusia (n = 3), diarrhea (n = 3), increased alanine aminotransferase (n = 3), increased aspartate aminotransferase (n = 3), increased blood creatinine (n = 3), paresthesia (n = 3), and increased weight (n = 3).

Treatment-related adverse events resulted in the dose interruptions in 6 patients, dose reductions in 5 patients, and treatment discontinuations in 1 patient.

“In line with previous reports, entrectinib was associated with a manageable safety profile in patients with 

 fusion-positive breast cancer,” lead study author Min Janice Lu, MD, of USC Norris Comprehensive Cancer Center, wrote in the poster.

Lu J, Blakely CM, Barve M, et al. Entrectinib in NTRK fusion-positive (NTRK-fp) breast cancer: updated data from STARTRK-2. Presented at: 2022 ESMO Breast Cancer Congress; May 3-5, 2022; Berlin, Germany. Poster 173P.

Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. 

. 2015;5(1):25-34. doi:10.1158/2159-8290.CD-14-0765

Wu S, Shi X, Ren X, Li K, Pang J, Liang Z. Evaluation of NTRK gene fusion by five different platforms in triple-negative breast carcinoma. 

. 2021;8:654387. doi:10.3389/fmolb.2021.654387

Demetri GD, Braud FD, Drilon A, et al. Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive solid tumors. 

. 2022;28(7):1302-1312. doi:10.1158/1078-0432.CCR-21-3597

Lu J, Blakely CM, Le Tourneau C, et al. Efficacy and safety of entrectinib in NTRK fusion-positive (NTRK-fp) breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual. Abstract PS11-28.

Basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK gene rearrangements (fusions) (STARTRK-2). ClinicalTrials.gov. Updated May 3, 2022. Accessed May 11, 2022. 

https://clinicaltrials.gov/ct2/show/NCT02568267

This article was originally published on OncLive as “Entrectinib Continues to Yield Promising Data in NTRK Fusion–Positive Breast Cancer”

Articles

Entrectinib elicited encouraging responses in patients with breast cancer that harbors NTRK fusions, according to updates from the phase 2 STARTRK-2 trial.

Entrectinib Generates Favorable Outcomes in NTRK Fusion+ Breast Cancer

HER2-positive breast cancer who also harbor brain metastases and were enrolled in the phase 2 TUXEDO-1 trial (NCT04752059) derived clinical benefit from treatment with fam-trastuzumab deruxtecan-nxki (Enhertu), according to data presented at the European Society for Medical Oncology Breast Cancer Congress 2022.

Among the 15 patients in the intention-to-treat (ITT) population, the objective response rate (ORR) via response assessment in neuro-oncology criteria was 73.3% (95% CI, 48.1%-89.1%). Bartsch noted that in the analysis 1 patient was found to have dural brain metastases only resulting in 14 patients meeting protocol requirements. The ORR among these patients was 78.6%. The clinical benefit rate in the ITT population was 86.7% and 92.9% in the per-protocol population.

“Brain metastases are a common and devastating complication of HER2-postitive breast cancer,” Rupert Bartsch, MD, associate professor, codirector of the Brain Metastases Program, and a consultant for hematology and medical oncology in the Department of the Medicine I, Clinical Division of Oncology at the Medical University of Vienna in Austria, said. “Local therapy has long been the main stay of treatment, but recent years have seen growing interest in systemic treatments as well.”

Data from combination regimens of HER2 tyrosine kinase inhibitors (TKIs), such as lapatinib (Tykerb) or neratinib (Nerlynx) plus capecitabine, have yielded clinically relevant activity for patients with HER2-positive breast cancer and brain metastases who progress after local therapy.

The standard of care for these patients was defined in results of the HER2CLIMB trial (NCT02614794), in which tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine reduced the risk of intracranial progression with a median central nervous system (CNS) progression-free survival (PFS) of 9.9 months (95% CI, 8.0-13.9) vs 4.2 months (95% CI, 3.6-5.7) with trastuzumab and capecitabine alone (HR, 0.32; 95% CI, 0.22-0.48; 

 < .00001).4 A 42% reduction in the risk of death was also observed among the 198 patients with brain metastases who received the investigational approach vs the 98 patients who received placebo (HR, 0.58; 95% CI, 0.40-0.85; 

Data from trials such as the DEBBRAH trial (NCT04420598) have suggested a role for antibody-drug conjugates in patients with brain metastases, Bartsch said.

TUXEDO-1 is a single-center, single-arm trial for patients with histologically confirmed HER2-positive breast cancer with newly diagnosed brain metastases or brain metastases progressing after local therapy for whom there is no indication for immediate local therapy available. Prior exposure to trastuzumab and pertuzumab (Perjeta) were required and prior exposure to ado-trastuzumab emtansine (T-DM1; Kadcyla) was permitted.

Patients received trastuzumab deruxtecan at the recommended dose of 5.4 mg/kg intravenously once every 3 weeks until progression or unacceptable toxicity.

At baseline, patients had a median age of 69 years (range, 30-76) with 80% of patients having the presence of visceral metastases and 80% of patients having HER2-positive/Luminal B disease. Prior treatment with T-DM1 was reported among 60% of patients and prior laptatinib was reported among 26.7%. In terms of prior treatment for brain metastases, 60% of patients had progressive brain metastases after local therapy at baseline. The median number of prior lines of therapy was 2 (range, 1-5).

Investigators also reported other secondary outcome measures. The median overall survival was not reached and the median PFS was 14 months (95% CI, 11–not reached) at a median follow-up of 11 months (range, 3-17). The extracranial response rate among 13 patients with extracranial metastases was 27.8% and was 62.5% among 8 patients who had measurable extracranial disease at baseline.

In terms of safety, most adverse effects (AEs) were grade 1/2 the most common of which were fatigue (66.7%), nausea (46.7%), anemia (46.6%) neutropenia (46.6%), and constipation (40%). Grade 3 AEs included fatigue (15.3%), anemia (6.7%), diarrhea (6.7%), dyspnea (6.7%), and urinary tract infection (6.7%).

AEs of special interest included 1 instance of ejection fraction decrease which was grade 3 and 1 instance interstitial lung disease which was grade 2 and was resolved after 6 weeks of corticosteroid treatment, according to Bartsch. Further, 6 serious AEs were reported in a total of 4 patients and 1 patient experienced grade 5 urosepsis which was not related to treatment.

“Global health status, physical function, and emotional function were maintained over the entire treatment period with an initial drop seen in the first weeks of therapy,” Bartsch said. “Importantly, in a trial conducted in patients with active brain metastases, cognitive function was maintained over the entire treatment period.”

Bartsch R, Berghoff AS, Furtner J, et al. Trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients with active brain metastases: primary outcome analysis from the TUXEDO-1 trial. Presented at: European Society for Medical Oncology Breast Cancer Congress 2022. May 3-5, 2022; Berlin, Germany.

Lin NU, Diéras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. 

. 2009;15(4):1452-1459. doi:10.1158/1078-0432.CCR-08-1080

Freedman RA, Gelman RS, Anders CK, et al; Translational Breast Cancer Research Consortium. A phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. 

. 2019;37(13):1081-1089. doi:10.1200/JCO.18.01511

Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. 

. 2020;38(23):2610-2619. doi:10.1200/JCO.20.00775

This article was originally published on OncLive as “Evidence Grows to Support Trastuzumab Deruxtecan in Patients With HER2+ Breast Cancer and Active Brain Metastases”

Patients with HER2-positive breast cancer who also have brain metastases experienced clinical benefit with fam-trastuzumab deruxtecan-nxki in the phase 2 TUEXEDO-trial.

Trastuzumab Deruxtecan Continues to Elicit Responses in HER2+ Breast Cancer With Active Brain Metastases

Single nucleotide polymorphism (SNP) genotyping could be used to predict radiation dermatitis in patients with breast cancer, according to findings that were presented during the 47th Annual Oncology Nursing Society (ONS) Congress.

Through an evaluation of 16 cohort studies, 13 of which had a low risk of bias, the following 7 genotypes were found to be associated with severe radiation dermatitis: 

Lower radiation dermatitis was found in those with 

“[This association] can be used to contribute to planning of radiation therapy as well as improve the nursing follow-up of patients most likely to develop severe radiation dermatitis, based on clinical and genetic assessment,” lead study author Beatriz Aguiar, of the University of Brasilia in Brazil, said in a virtual presentation of the data.

Radiation dermatitis, which occurs in an estimated 95% of patients with breast cancer who are undergoing radiation, typically has an impact on the continuity of treatment for patients with breast cancer, along with their quality of life and their body image.

Prior radiogenomic studies have evaluated the potential of SNPs to predict the risk of severe radiation dermatitis, the authors noted in their poster.

In the analysis presented at the ONS Congress, investigators sought to identify whether SNPs are associated with the rate of severe radiation dermatitis with the use of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. The authors also performed the search at CINAHL, Cochrane CENTRAL, EMBASE, LILACS, PubMed, Scopus, and Web of Science in the gray literature and in a reference list of articles.

Additionally, the Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies tool was utilized to assess the risk of bias from the individual studies. Investigators conducted a meta-analysis of 16 cohort studies to evaluate the association between SNPs and severe radiation dermatitis. Grading of Recommendation, Assessment, Development, and Evaluation was also utilized to assess evidence.

Further findings showed that there was a low certainty of evidence for association with severe radiation dermatitis in the 

 gene – SNP rs3957356 – CT genotype (odds ratio [OR]: 5.57; 95% CI, 1.73-17.87; 

 = .004). This was also the case in the GG genotype with the 

 gene – SNP rs2282367 (OR, 2.03; 95% CI, 1.18-3.48; 

Aguiar B, Normando AG, Guerra E, et al. Association of single nucleotide polymorphisms with severity of acute radiation dermatitis in breast cancer patients: systematic review and meta-analysis. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P7.

Single nucleotide polymorphism (SNP) genotyping could be used to predict radiation dermatitis in patients with breast cancer.

Single Nucleotide Polymorphism Genotyping Could Predict Severe Radiation Dermatitis in Breast Cancer 

The FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment option for adults with unresectable or metastatic HER2-positive breast cancer and have already received anti–HER2-based treatments in the metastatic, neoadjuvant or adjuvant settings, and have experienced disease recurrence during or within 6 months of therapy completion.

Previously, in December 2019, the antibody-drug conjugate was granted an accelerated approval from the regulatory agency for use in adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti–HER2-based regimens in the metastatic setting.

The multicenter, open-label, DESTINY-Breast03 trial (NCT03529110) served as the confirmatory trial for the approval.

 To be eligible for enrollment, patients needed to have HER2-positive, unresectable or metastatic breast cancer that had progressed during or following treatment with trastuzumab (Herceptin) and a taxane in the context of advanced or metastatic disease or that had progressed within 6 months following neoadjuvant or adjuvant treatment involving trastuzumab or a taxane. Those with clinically stable, previously treated brain metastases were permitted.

If patients had brain metastases that were symptomatic or required treatment; if they previously received a HER2-targeted ADC, including trastuzumab emtansine (Kadcyla; T-DM1), for metastatic disease; or if they had a history of noninfectious ILD for which they had been given glucocorticoids, they were excluded.

A total of 524 study participants were randomized 1:1 to receive intravenous (IV) trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks (n = 261) vs IV T-DM1 at 3.6 mg/kg every 3 weeks (n = 263). Treatment was administered until disease progression or intolerable toxicity.

Stratification factors included hormone receptor status (positive vs negative), previous treatment with pertuzumab (Perjeta; yes vs no), and history of visceral disease (yes vs no).

The primary end point of the trial was progression-free survival (PFS) per blinded independent central review (BICR), and overall survival (OS) served as a key secondary end point. Other end points included overall response per BICR and investigator assessment, investigator-assessed PFS, and safety.

Demographic and baseline disease characteristics were found to be comparable between the 2 treatment arms, and were also determined to be largely representative of the overall population of patients with HER2-positive breast cancer.

Of note, 49.8% of those in the investigative arm and 46.8% of those in the control arm had received 1 prior line of therapy, not including endocrine therapy, for metastatic disease. Moreover, 62.1% of those in the trastuzumab deruxtecan arm vs 60.1% of those in the T-DM1 arm previously received pertuzumab. Stable brain metatases were noted in 23.8% and 19.8% of patients, respectively.

The median follow-up in the investigative arm was 16.2 months (range, 0-32.7) vs 15.3 months (range, 0-31.3) in the control arm. Trastuzumab deruxtecan significantly improved PFS vs T-DM1. Specifically, the median PFS was not yet reached (95% CI, 18.5–not estimable [NE]) in the investigative arm vs 6.8 months (95% CI, 5.6-8.2) in the control arm (HR, 0.28; 95% CI, 0.22-0.37; 

Moreover, at 12 months, 75.8% (95% CI, 69.8%-80.7%) of patients who received trastuzumab deruxtecan were still alive and free of disease progression vs 34.1% (95% CI, 27.7%-40.5%) of those who were given T-DM1.

Per investigator assessment, the median PFS in the investigative arm was 25.1 months (95% CI, 22.1-NE) vs 7.2 months (95% CI, 6.8-8.3) in the control arm (HR, 0.26; 95% CI, 0.20-0.35; 

Notably, the PFS benefit achieved with trastuzumab deruxtecan over T-DM1 was noted across all subsets of patients examined, irrespective of prior lines of therapy received.

At the data cutoff of May 21, 2021 for the interim analysis, 94.1% (95% CI, 90.3%-96.4%) of patients in the investigative arm will still alive at 12 months vs 85.9% (95% CI, 80.9%-89.7%) of those in the control arm (HR, 0.55; 95% CI, 0.36-0.86; 

=.007). The difference between the treatment arms was not found to be statistically significant, although the data are immature.

Moreover, the objective response rate based on the patients with measurable disease assessed by BICR at baseline was 82.7% (95% CI, 77.4%-87.2%) with trastuzumab deruxtecan vs 36.1% (95% CI, 30.0%-42.5%) with T-DM1.

Regarding safety, the most frequent toxicities experienced by patients who received trastuzumab deruxtecan were nausea, fatigue, vomiting, alopecia, constipation, anemia, and musculoskeletal pain.

Serious effects that were reported in more than 1% of patients who received the ADC included vomiting, ILD, pneumonia, pyrexia, and urinary tract infection.

The FDA stated that prescribing information for trastuzumab deruxtecan includes a Boxed Warning to advise of the risk of ILD and embryo-fetal toxicity.

FDA grants regular approval to fam-trastuzumab deruxtecan-nxki for breast cancer. News release. FDA. May 4, 2022. Accessed May 4, 2022. https://bit.ly/3ybhZLL

Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. 

. 2022;386(12):1143-1154. doi:10.1056/NEJMoa2115022

Fam-trastuzumab deruxtecan-nxki is now an FDA-approved regimen for the treatment of patients with unresectable or metastatic HER2-positive breast cancer.

FDA Approves Trastuzumab Deruxtecan for Unresectable or Metastatic HER2+ Breast Cancer

Bioimpedance spectroscopy (BIS) is a more accurate method of identifying which breast cancer survivors will need compression intervention for subclinical lymphedema compared with tape measurement (TM) to prevent chronic lymphedema, according to findings from a study published in Lymphatic Research and Biology.

 Moreover, the technology is easy to use and patient friendly, according to principal investigator Sheila H. Ridner, PhD, RN, FAAN. 

“It is as easy to use as putting someone on a scale and getting their weight,” Ridner, research professor at Vanderbilt University School of Nursing in Nashville, Tennessee, explained in an interview with Oncology Nursing News®, noting that the underlying technology is based on electrical currents that measure the fluid between the cells. “It’s very simple. It’s very quick.”

 Results from the PREVENT study (NCT02167659) showed that among patients who received compression intervention after early lymphedema detection, only 7.9% of patients who were assessed through BIS developed chronic lymphedema. In comparison, 19.2% of patients who were assessed using TM developed this chronic disease. These statistically significant results (P = .016) may translate into an absolute reduction of 11.3% and a relative reduction of 59% in lymphedema progression at 3 years, according to the study authors. 

Chronic breast cancer–related lymphedema (C-BCRL) has become more concerning as the rate of breast cancer survivorship has continued to rise. As such, the number of patients affected by pain, infections, limited arm function, reduced quality of life, and very expensive therapies because C-BCRL has likely grown in recent years. 

“To me, it is [a] numbers game,” Ridner said. “More survivors equal more opportunity for chronic pain…but if we can keep people from getting it, then there is a whole set of lymphedema-related pain issues breast cancer survivors may be able to avoid.” Currently, 5% of patients who undergo breast-conserving surgery with sentinel lymph node biopsy (SLNB) alone experience C-BCRL, as well as more than 50% of patients who undergo axillary lymph node dissection, regional node irradiation, and/or taxane-based chemotherapy. These statistics underscore the value of proper C-BCRL identification in breast cancer survivors, the authors explained. However, early-stage C-BCRL identification can be challenging. 

Although subclinical disease and extracellular fluid occurs before changes become visible, C-BCRL diagnoses do not typically occur until a visible change or symptom has become apparent. Therefore, investigators decided to use BIS to identify early-stage subclinical lymphedema and to initiate treatment to prevent C-BCRL (defined as ≥ 10% arm volume change from baseline, requiring complex decongestive physiotherapy CDP) in survivors. BIS technology can recognize extracellular fluid change and has been found to improve patient outcomes when combined with short-course compression therapy, as was administered in this study. 

“The BIS can pick up changes in the fluid that exists between each human cell. [TM] can’t do that, pyrometry can’t do that, and MRI can’t do that,” Ridner said. “The earlier you catch this fluid, the less likely you are to have a large inflammatory process in the arm. We are now able to identify the subclinical lymphedema when there is less inflammation that needs to be treated.” 

The stratified, randomized, international trial included patients with recent breast cancer diagnoses who were undergoing either mastectomy/partial mastectomy, axillary treatment (dissection, SLNB > 6 nodes or radiation), radiation therapy, or taxanebased therapy. Exclusion criteria included history of breast cancer, neoadjuvant chemotherapy, and previous radiation on the breast, chest wall, or axilla. 

Participants were randomized 1:1 following a postsurgery eligibility reassessment and underwent prospective surveillance via either BIS or TM. If surveillance detected C-BCRL, patients were to wear a class 2 (23-32 mm Hg, mediven flat-knit custom or Harmony circular knit) compression sleeve and gauntlet for 12 hours per day for 4 weeks. 

Patients were recruited between June 24, 2014, and September 11, 2018. In total, 442 evaluable patients were enrolled in the BIS cohort, and 437 evaluable patients were enrolled in the TM cohort. The median follow-up was 32.9 months. 

Presurgical measurements were collected at baseline for both the BIS or TM cohorts; collected again at 3, 6, 12, 18, 24, and 36 months; and again following compression intervention. Some sites also conducted a 15- and 21-month follow-up. 

The BIS evaluation was conducted via L-Dex U400, and TM evaluation was conducted using Gulick II tape. The patients’ arms were measured twice at 10-cm increments, starting at the wrist and continuing up to 50 cm above the wrist. A truncated cone formula was used to automatically calculate arm volume. Ultimately, the number of patients whose disease progressed following compression intervention was lower in the BIS group than the TM group (7.9%, n = 7 vs 19.2%; n = 23, relative risk, 0.41; 95% CI, 0.13-0.81; absolute reduction 11.3%; 95% CI, 2.3-20.3; P = .016). 

Notably, Ridner’s patients have expressed satisfaction with the technology. “The first patient I ever measured [with BIS] loved the technology,” she said. “Patients can tell [TM] techniques vary from therapist to therapist, doctor to doctor, or nurse to nurse. [BIS] standardizes the way you do the measurement.” 

“Surveillance with early intervention is clearly in the best interest of the patients,” Ridner said. “We can change outcomes in this population and address not only the chronicity of the lymphatic issues many of these patients have but also reduce the discomfort they may experience.”

Ridner SH, Dietrich MS, Boyages J, et al. A comparison of bioimpedance spectroscopy or tape measure triggered compression intervention in chronic breast cancer lymphedema prevention. 

. 2022;10.1089/lrb.2021.0084. doi:10.1089/lrb.2021.0084

Patients who underwent prospective surveillance with bioimpedance
spectroscopy were less likely to develop chronic breast cancer–related
lymphedema compared with patients who were assessed with tape measure.

Bioimpedance Spectroscopy May Play a Large Role in Proactively Preventing Chronic Lymphedema

 (BIS) allows oncology nurses to be more proactive in managing subclinical lymphedema, according to Sheila Ridner, PhD, RN, FAAN.

Ridner, a research professor at Vanderbilt University School of Nursing, was co-principal investigator in the 

 (NCT02167659), which found patients who received compression intervention after assessment with BIS were less likely to develop lymphedema compared with those who received compression intervention after assessment with tape measure. The percentage of patients who developed lymphedema in these 2 populations were 7.9% and 19.2%, respectively (

These findings suggest that the oncology care team can leverage outcomes by proactively identifying and managing this adverse event without necessarily involving lymphedema specialists, explains Ridner.

“Nurses and research assistants did the measurements in the study,” she said. “We have [shown] that the cancer treatment team can do the initial diagnosis and we can have the nurses or research aids fit the patients for the garment and run that 30-day intervention.”

“That's important because there is a shortage of trained lymphedema therapists,” Ridner explained. “Now we know that multidisciplinary breast cancer teams can do this short-term intervention [along with] surveillance; if you can get the right people to do the right pieces of patient care, then you can take some of the stress off some of the highly burdened lymphedema clinics.”

However, implementing BIS technology will start with nurse education and advocacy, she noted.

“Nurses are the advocates for patients in this world,” she concluded. “Now [we] have an evidence base that they can use to become informed advocates.”

Videos

Sheila Ridner, PhD, RN, FAAN, discusses the implications of the PREVENT study and how oncology nurses can advocate for patients with breast cancer. 

Oncology Nurses Can Help Better Prevent Chronic Lymphedema With BIS Technology 

A combination of resistant exercises (such as lifting weights) and endurance exercises (such as walking or jogging) have been found to help patients with breast cancer combat depression and improve quality of life (QOL) and social functioning by improving cardiorespiratory fitness muscular endurance and muscular strength, according to a systematic review and meta‑analysis recently published in 

Furthermore, the findings demonstrated that combining resistance exercises with endurance exercises also helped patients significantly reduce fatigue. These data are important, the study authors noted, because fatigue affects between 62% and 85% of patients receiving adjuvant therapies—such as chemotherapy, radiotherapy, hormone therapy, and forms of targeted therapy—for breast cancer.

“The findings presented show combined exercise interventions elicit significant enduring benefits to global fatigue during adjuvant therapy in breast cancer patients,” the authors said. “They also suggest a lasting clinical benefit for combined interventions to improving the remaining factors (cardiorespiratory fitness, depression, muscular endurance, muscular strength, QOL, and social functioning) thus improving physical fitness and mental wellbeing.”

Investigators canvassed PubMed, BioMed Central, Scopus, Web of Science Core collection, Cochrane Library, and Ovid for records containing the search terms “endurance” and “resistance exercise” with “breast cancer.” Initially, 9488 records were identified as evaluable. Criteria for eligibility dictated that the studies needed to be a published, randomized, controlled clinical trial with a complete database, contain assessment on endurance/aerobic impact on patients with breast cancer with at least 20 minutes of exercise per session, be written in English, and be published between 2010 and 2020.

After screening and assessing the records for eligibility and qualitative synthesis, investigators had 18 total studies evaluable for the meta-analysis.

Overall, investigators found that the 2 exercises combined elicited a positive effect on muscular strength size (standardized mean difference [SMD], 0.47; 95% CI, −0.46 to 1.40; I2 = 87%; 

 = .235). This analysis also achieved optimal power (91.86%) and prediction intervals anticipate this positive effect to appear again in future studies.

Similarly, the combined intervention was linked to improved QOL among the patient population (SMD, 0.18; 95% CI, −0.27 to 0.63; I2 = 31%; 

 = .295). Prediction models also anticipate this positive effect will appear again in upcoming analyses.In terms of social functioning, a positive effect was observed (SMD, 0.26; 95% CI, − 0.33 to 0.86; 

 = .39), but power analysis and prediction intervals were not able to be carried out.

For depression, the effect of the combined exercise types was inconclusive, but investigators did determine a small negative effect size for resistance exercise alone in female patients undergoing adjuvant therapy (SMD, − 0.02; 95% CI, − 0.28 to 0.24; I2 = 0%; 

 = .895). However, the power analysis was low (5.26%)

Finally, in terms of global fatigue, the combined exercise efforts yielded a significant negative effect size (SMD, −0.26; 95% CI, − 0.46 to − 0.07; I2 = 0%; 

 = .008). Prediction intervals suggested that this effect will be replicated in future studies.

In conclusion, although acknowledging that more research is needed, the authors expressed hope that these findings will “progress literature towards improving the process of adjuvant treatment for breast cancer patients to minimize its detrimental side effects. This will help those undergoing aggressive cancer treatments to return to a functional lifestyle posttreatment.”

Mok J, Brown MJ, Akram EC, Morris MA. The lasting effects of resistance and endurance exercise interventions on breast cancer patient mental wellbeing and physical fitness. 

 2022;12:2504. doi:10.1038/s41598-022-07446-3

Exercise improves physical and mental side effects of breast cancer treatments, new study finds. Loughborough University. News release. March 25, 2022. Accessed March 30, 2022. https://bit.ly/3DqR8eY

New data demonstrate that regular exercise can help patients with breast cancer mitigate the physical and mental treatment–related side effects that might impact their quality of life. 

Resistance and Endurance Exercises Showcase Benefit for Patients With Breast Cancer

The approval of relatlimab/nivolumab (Opdualag) is exciting because it represents a new immunotherapy combination for patients with unresectable or metastatic melanoma, according to Hussein A. Tawbi, MD, PhD.

However, the newly approved agent will not replace PD-1/CTLA-4 combination immunotherapy, he explained. Rather, the 2 will now co-exist in the treatment landscape, providing oncology care teams multiple therapeutically relevant treatment options to offer their patients.

The fixed-dose PD-1/LAG-3 inhibition regimen was 

 on the indication of unresectable or metastatic melanoma for adults of at least 12 years of age and who weigh at least 40 kg. Notably, the approval was based off findings from the RELATIVITY-047 study, which demonstrated the combination 

Tawbi, a professor of the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, and principal investigator in the RELATIVITY-046 trial, recently met with 

todiscuss what this approval means for patients with unresectable or metastatic melanoma.

“It is a really important development for our patients,” he said. “We know that single agent PD-1 has been capable of curing almost 40% of our patients with unresectable or metastatic melanoma. We really think that this [agent] will add a significant proportion of [successfully treated patients].”

“The one thing that we will always need to be very clear about is that this study did not compare the combination [of nivolumab/relatlimab] to the combination of PD-1/CTLA-4 inhibition,” noted Tawbi.

“There will be decision making in the first-line setting, [we will ask ourselves], ‘can I rely on nivolumab/relatlimab or do I give nivolumab/ipilimumab [Yervoy] despite the toxicity?’ From my perspective, that combination of nivolumab/relatlimab will replace single-agent PD-1 inhibitors.”

Hussein A. Tawbi, MD, PhD, principal investigator of the phase 2/3 RELATIVITY-046 trial, highlights the importance of relatlimab/nivolumab’s recent FDA approval in melanoma.          

Expert Talks Significance of Relatlimab/Nivolumab Approval for Metastatic Melanoma

Managing nausea and monitoring complete blood counts (CBC) for drops in hemoglobin are crucial when administering olaparib (Lynparza) to patients with germline 

-mutated, HER2-negative, high-risk early breast cancer, according to Charles E. Geyer, MD, FACP.

 as a treatment for patients with this disease type and who have already undergone chemotherapy before or after surgery, after 

 demonstrated that the oral PARP inhibitor resulted in a 42% improvement in invasive disease-free survival compared with placebo.

®, Geyer, who is chief scientific officer of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, and an investigator in the OlympiA trial, 

 to discuss dosing strategies and adverse event management with olaparib.

The starting dose in OlympiA was 300 milligrams twice a day, Geyer explained. “The medication comes in tablets, there are 150 milligram tablets that are a greenish color, and 100 milligram tablets, which are yellow. Patients start out by taking 2 green tablets twice a day.”

Furthermore, because olaparib is taken twice a day and can cause nausea (particularly in the first month), nurses should stress the importance of taking the agent with food.

“Doctors on the study found that sometimes patients do not hear how important it is to take [olaparib] with food,” noted Geyer. “It can be a light meal [or] a snack, but we do [stress the importance of] taking it with food. That is a hugely important message.”

Another important consideration when treating patients with olaparib is anemia, he continued. He emphasized the importance of adjusting dosage if a patient’s hemoglobin begins to drop, adding that since patients will need to take the agent for 1 year, it is important to find a dose that is manageable.

“Sometimes hemoglobin can drop quick enough [that] patients get symptomatic and might require transfusions; about 6% of the patients required a blood transfusion, but only 2% required more than 1 transfusion,” said Geyer. “It is important [to monitor] complete blood counts carefully, and [understand] that it is okay to hold the drug.”

“Sometimes patients feel, ‘I need to take it, I can take it, and I don't feel bad enough to stop it.’ However, you don't want the hemoglobin to drop: [the treatment] is a marathon—[they take it] for a whole year, so we want to work to find the correct dose. That will be important to keep in mind,” he concluded.

Charles E. Geyer, MD, FACP, discusses dosing strategies and adverse event management with olaparib.

Breast Cancer