Research Spotlight

Huang, M., Haiderali, A., Fox, G. E., Frederickson, A., Cortes, J., Fasching, P. A. and O’Shaughnessy, J. (2022). “Economic and Humanistic Burden of Triple-Negative Breast Cancer: A Systematic Literature Review.” Pharmacoeconomics.

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BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. OBJECTIVE: The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. METHODS: A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. RESULTS: The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around $20,000 to over $100,000 in stage I-III TNBC and from $100,000 to $300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from $207 to $1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. CONCLUSION: TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.

Geyer, C. E., Jr., Sikov, W. M., Huober, J., Rugo, H. S., Wolmark, N., O’Shaughnessy, J., Maag, D., Untch, M., Golshan, M., Ponce Lorenzo, J., Metzger, O., Dunbar, M., Symmans, W. F., Rastogi, P., Sohn, J., Young, R., Wright, G. S., Harkness, C., McIntyre, K., Yardley, D. and Loibl, S. (2022). “Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase 3 trial.” Ann Oncol.

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BACKGROUND: Primary analyses of the phase 3 BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. DESIGN: Women with untreated stage II-III TNBC were randomized (2:1:1) to paclitaxel (weekly for 12 doses) plus either: (a) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (b) carboplatin plus veliparib placebo; or (c) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide (AC) every 2‒3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio [HR] for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 (95% confidence interval [CI] 0.43‒0.92, P=0.02), but 1.12 (95% CI 0.72‒1.72, P=0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, HR for EFS was 0.57 (95% CI 0.36‒0.91, P=0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSION: Improvement in pCR with addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, while adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by AC neoadjuvant chemotherapy for early stage TNBC.

Nguyen, A. D., Ellison, A., Reddy, C. A., Mendoza, R., Podgaetz, E., Ward, M. A., Souza, R. F., Spechler, S. J. and Konda, V. J. A. (2022). “Spastic secondary contractile patterns identified by FLIP panometry in symptomatic patients with unremarkable high-resolution manometry.” Neurogastroenterol Motil: e14321.

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BACKGROUND: Functional lumen imaging probe (FLIP) panometry can show spastic secondary contractile patterns of unclear significance in symptomatic patients who have no esophageal obstructive disorders, and no motility disorders on high-resolution manometry (HRM). METHODS: We retrospectively analyzed non-obstructed, symptomatic patients with HRM findings of no motility disorder or ineffective esophageal motility (IEM) for whom spastic secondary contractile patterns identified by FLIP panometry were used to guide treatment. Symptoms were scored using the Brief Esophageal Dysphagia Questionnaire (BEDQ). KEY RESULTS: We identified ten symptomatic patients treated at our medical center who met inclusion criteria (seven women; mean age 56 years; eight no motility disorder, two IEM). On FLIP panometry, seven had spastic secondary contractions at 60 ml, two at 40 ml, and one at both 40 ml and 60 ml balloon volumes. Eight patients (80%) had improvement in BEDQ scores with therapies that targeted the spastic secondary contractile patterns identified by FLIP (five botulinum toxin injection, two Esoflip dilation, and one Heller myotomy). Interestingly, review of HRM tracings revealed that all patients had a novel HRM finding of mid-vertical pressurization in at least 20% swallows, with seven exhibiting this finding in >50% of swallows. CONCLUSIONS: This case series demonstrates that treatments targeting spastic secondary contractions identified by FLIP panometry can result in symptomatic improvement in patients with no obstructive disorder and no diagnostic motility disorder on HRM. In such patients, we have identified the novel HRM finding of mid-vertical pressurization, which might be the manometric manifestation of spasm limited to the mid-esophagus.

Cochran, J. M., Alam, A. and Guerrero-Miranda, C. Y. (2022). “Importance of right heart catheterization in advanced heart failure management.” Rev Cardiovasc Med 23(1): 12.

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Patients with chronic congestive heart failure belong to a population with reduced quality of life, poor functional class, and increased risk of mortality and morbidity. In these patients, assessment of invasive hemodynamics both serves therapeutic purposes and is useful for stratification roles. The right heart catheterization has become a cornerstone diagnostic tool for patients in refractory heart failure or cardiogenic shock, as well as for the assessment of candidacy for heart replacement therapies, and the management of patients following mechanical circulatory assist device implantation and heart transplantation.

Thaçi, D., Strober, B., Gordon, K. B., Foley, P., Gooderham, M., Morita, A., Papp, K. A., Puig, L., Menter, M. A., Colombo, M. J., Elbez, Y., Kisa, R. M., Ye, J., Napoli, A. A., Wei, L., Banerjee, S., Merola, J. F. and Gottlieb, A. B. (2022). “Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial.” Dermatol Ther (Heidelb) 12(2): 495-510.

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INTRODUCTION: Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. METHODS: Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician’s Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. RESULTS: Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient’s life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. CONCLUSION: Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02931838.