Measuring Therapeutic Intervention Impact, Receptiveness for Patients With Breast Cancer

Patients undergoing chemotherapy for breast cancer experience a myriad of adverse effects (AEs) such as nausea, vomiting, fatigue, and sleep disturbance. Much of these issues can be further exacerbated by stress and anxiety commonly associated with diagnosis and treatment. If left untreated, these related effects can impact the quality of life (QOL) for patients and impede overall care.

Abstract results presented Thursday at the 2019 San Antonio Breast Cancer Symposium focus on the efficacy of therapeutic interventions to curb chemotherapy-induced effects and heightened screening to ease anxiety for patients with early stage breast cancer at risk for developing a metastatic diagnosis. A yoga program, a fixed combination of netupitant/palonosetron (NEPA), and minimal residual disease (MRD) screening for therapeutic intervention serve as the focus of the abstracts.

Effectiveness of Yoga for Patients with Breast Cancer Undergoing Chemotherapy

To improve mental health of patients with breast cancer experiencing chemotherapy-induced effects, researchers sought to expand on the limited options available by testing the effectiveness of yoga, an increasingly popular mind-body practice.¹

A pilot randomized controlled study was conducted to evaluate the feasibility and efficacy of yoga on chemotherapy-related symptoms and QOL in 50 women with stage 1-3 breast cancer who were scheduled to undergo neoadjuvant or adjuvant chemotherapy. These patients were randomized to start yoga immediately (yoga group) or in 3 months (waitlist control group):

• Intervention consisted weekly 60-minute yoga classes for 12 weeks
• Patients completed self-reported questionnaires, including the Functional Assessment of Cancer Therapy-Breast (FACT-Breast), Anxiety and Depression Scale (HADS), and the Pittsburgh sleep quality inventory (PSQI) at the start, 6 weeks, and 12 weeks after being randomized
• Group analyses performed using 2-sample t-test for baseline, 6, and 12-week time points

Of the study cohort, 66% of patients had no prior yoga experience, and average class participation rate was 55%. Compared to the waitlist control group, overall study results exhibited the clinical benefit found in the yoga group as there was a significant reduction in reported nausea at 12 weeks (P = .014), trends toward statistical significance in improvement in sleep efficiency (P = .075) and overall physical well-being (P = 0.090) at 12 weeks, and in patients with reduced QOL at baseline, there was a significant improvement in severity of depression (P = .050) at 6 weeks. Additionally, a trend towards improvement in overall physical well-being at 12 weeks (P = .094) was found in the yoga group compared to the control group.

Study authors noted that weekly yoga participation is a feasible option in patients with breast cancer receiving adjuvant or neoadjuvant chemotherapy and that study results show its potential effectiveness. “Larger studies are warranted to further assess the efficacy of yoga in reducing chemotherapy-associated symptoms in patients with early stage breast cancer,” said the study authors.

Efficacy of NEPA on QOL for Prevention of Chemotherapy-Induced Nausea, Vomiting

NEPA is an oral, fixed-dose combination (netupitant = 300 mg; palonosetron = 500mg) approved for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients with cancer receiving highly (HEC) or moderately emetogenic (MEC) chemotherapy. Researchers aimed to measure the effectiveness of the drug through a non-interventional study (AkyPRO)² that evaluated the primary endpoint of QOL and secondary endpoints of efficacy and safety for NEPA as a primary preventive agent for CINV associated to MEC or HEC:

• Study evaluated NEPA in 986 patients with breast cancer receiving single day or 2 day MEC or HEC
• QOL recorded by functional living index-emesis questionnaires, with patients and physicians documenting overall antiemetic efficacy on a 4-point scale (very good, good, satisfactory, poor)
• Efficacy of NEPA indicated by complete response (CR: no vomiting, no rescue medication)
• Additional medication and adverse events recorded in patient diaries over 3 consecutive chemotherapy cycles

In the patient cohort, 80% received HEC and the remaining 20% received MEC. The study found that 84% of patients with breast cancer administered NEPA had no adverse impact on daily life due to vomiting in all analyzed cycles. Furthermore, more than 93% of patients reported no emesis and more than 81% reported CR during the 5 days post-chemotherapy during all 3 cycles. However, nausea was more difficult to control as 37% of patients documented to have suffered from nausea 1 or more times during the 5 days following chemotherapy, with 51%-56% reporting no impact of nausea on daily life.

Physician and patient assessments on the effectiveness of NEPA were found to be equally well, as physicians rated the medication as very good/good for 89% to 91% of patients in all 3 cycles. “Together with its convenient administration attributes of 1 single dose per chemotherapy cycle, NEPA might facilitate adherence to antiemetic guidelines and ultimately may improve CINV control,” said the study authors.

Patient-Reported Responsiveness, Outcomes of MRD Screening

As the study authors note, patients with early breast cancer have a 30% lifetime risk of developing incurable, distant metastatic disease.³ This risk can continue to impede QOL of patients after remission, but standard monitoring once definitive treatment is completed has remained a passive observation. Dormant bone marrow (BM) disseminated tumor cells (DTCs) have been shown to be independently associated with recurrence of disease in numerous studies, but assessment of DTCs is not performed in clinical practice because of acceptability concerns, logistics of BM aspiration, and a lack of established therapies targeting DTCs.

Researchers sought to examine acceptability of DTC screening by measuring patient attitudes, while additionally assessing feasibility and tolerability of BM DTC assessments. Assessments were completed through the PENN-SURMOUNT (Surveillance Markers of Utility for Recurrence after (Neo)adjuvant Therapy) screening study, a single center prospective, longitudinal cohort study examining BM and blood biomarkers of MRD among pts within 5 years of breast cancer diagnosis, who meet high risk criteria:

• Risk criteria include positive axillary nodes, triple negative biology, ER+ with Oncotype Dx ≥ 25 and/or high-risk Mammaprint, or residual disease after neoadjuvant chemotherapy
• 25 consenting women with stage 2-3 breast cancer underwent baseline outpatient BM aspiration and were surveyed at random to assess feasibility
• From SURMOUNT Study, researchers collected demographic and clinical characteristics of patients, and patient-centered survey data regarding feasibility and acceptability of the BMA administered within 48 hours of the procedure

In the pre-trial feasibility survey, 21 of the 25 (84%) patients indicated they were very/definitely interested in knowing if they had DTCs, with 18 of those 21 patients reporting moderate/definite interest in testing for DTC with BM aspiration after the procedure was explained. Additionally, 20 (95%) patients indicated moderate/definite interest in taking oral therapy to eradicate DTCs, 14 (67%) patients stated their commitment to a clinical trial regardless of having to undergo up to 3 additional BM aspirations, and only 1 patient stated they were less likely to undergo the trial after further information.

In the subsequent SURMOUNT study, 361 patients have been referred. Of the 167 patients eligible, 136 (81%) enrolled, with 21 (13%) still in screening. Additionally, 130 patients have had at least 1 BM aspiration with annual repeat screens in 37 (year 1) and 8 (year 2) and 39% traveled >50 miles to participate. “The SURMOUNT study shows that screening for DTCs is feasible and effective in identifying pts for therapeutic intervention targeting MRD to reduce recurrence,” said the study authors. The procedure was found to be well tolerated with rare post-BM aspiration symptoms experienced.

Reference

1. Chen T, Klein P, Xing T, et al. A yoga program for breast cancer patients undergoing chemotherapy: Effects on quality of life and chemotherapy-associated symptoms. Presented at the San Antonio Breast Cancer Symposium, San Antonio, Texas; December 10-14, 2019. Abstract: P2-12-03.
2. Schilling J, Busch S, Stefek A, et al. Quality of life data of breast cancer patients receiving a fixed combination of netupitant/palonosetron (NEPA) for prevention of chemotherapy-induced nausea and vomiting - a real life study. Presented at the San Antonio Breast Cancer Symposium, San Antonio, Texas; December 10-14, 2019. Abstract: P2-12-02.
3. Nivar I, Kauffman T, Bayne L, et al. Patient attitudes, experience and results of screening for minimal residual disease (MRD) for therapeutic intervention. Presented at the San Antonio Breast Cancer Symposium, San Antonio, Texas; December 10-14, 2019. Abstract: P2-12-01.