Research Spotlight

Johnston, S.R.D., Harbeck, N., Hegg, R., Toi, M., Martin, M., Shao, Z.M., Zhang, Q.Y., Martinez Rodriguez, J.L., Campone, M., Hamilton, E., Sohn, J., Guarneri, V., Okada, M., Boyle, F., Neven, P., Cortés, J., Huober, J., Wardley, A., Tolaney, S.M., Cicin, I., Smith, I.C., Frenzel, M., Headley, D., Wei, R., San Antonio, B., Hulstijn, M., Cox, J., O’Shaughnessy, J. and Rastogi, P. (2020). “Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).” J Clin Oncol Sep 20;JCO2002514. [Epub ahead of print.]. Jco2002514.

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PURPOSE: Many patients with HR+, HER2- early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS: This open-label, phase III study included patients with HR+, HER2-, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse-free survival, overall survival, and safety. RESULTS: At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION: Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2- node-positive EBC at high risk of early recurrence.

Kalinsky, K., Diamond, J.R., Vahdat, L.T., Tolaney, S.M., Juric, D., O’Shaughnessy, J., Moroose, R.L., Mayer, I.A., Abramson, V.G., Goldenberg, D.M., Sharkey, R.M., Maliakal, P., Hong, Q., Goswami, T., Wegener, W.A. and Bardia, A. (2020). “Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial.” Ann Oncol Sep 15;S0923-7534(20)42445-7. [Epub ahead of print.].

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BACKGROUND: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. PATIENTS AND METHODS: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2). CONCLUSIONS: SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). TRIAL REGISTRATION: ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.

Ranganath, P., Moore, A., Guerrero, M., Collins, J., Foley, T., Williamson, E. and Rajiah, P. (2020). “CT for Pre- and Postprocedural Evaluation of Transcatheter Mitral Valve Replacement.” Radiographics 40(6): 1528-1553.

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Transcatheter mitral valve replacement (TMVR) is a catheter-based interventional technique for treating mitral valve disease in patients who are at high risk for open mitral valve surgery and with unfavorable anatomy for minimally invasive edge-to-edge transcatheter mitral valve repair. There are several TMVR devices with different anchoring mechanisms, delivered by either transapical or transseptal approaches. Transthoracic echocardiography is the first-line imaging modality used for characterization and quantification of mitral valve disorders. CT is complementary to echocardiography and has several advantages, including high isotropic spatial resolution, good temporal resolution, large field of view, multiplanar reconstruction capabilities, and rapid turnaround time. CT is essential for multiple aspects of preprocedural planning. Accurate and reproducible techniques to prescribe the mitral annulus at CT have been described from which important measurements such as the area, perimeter, trigone-trigone distance, intercommissural distance, and septolateral distance are obtained. The neo-left ventricular outflow tract (LVOT) can be simulated by placing a virtual prosthesis in the CT data to predict the risk of TMVR-induced LVOT obstruction. The anatomy of the landing zone and subvalvular apparatus as well as the relationship of the virtual device to adjacent structures such as the coronary sinus and left circumflex coronary artery can be evaluated. CT also stimulates procedural fluoroscopic angles. CT can be used to evaluate the chest wall for transapical access and the atrial septum for transseptal access. Follow-up CT is useful in identifying complications such as LVOT obstruction, paravalvular leak, pseudoaneurysm, and valve embolization. Online supplemental material is available for this article.

Monticciolo, D.L. (2020). “Current Guidelines and Gaps in Breast Cancer Screening.” J Am Coll Radiol 17(10): 1269-1275

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Breast cancer is the most common nonskin cancer in women and the second leading cause of cancer death for women in the United States. Mammography screening is proven to significantly decrease breast cancer mortality, with a 40% or more reduction expected with annual use starting at age 40 for women of average risk. However, less than half of all eligible women have a mammogram annually. The elimination of cost sharing for screening made possible by the Affordable Care Act (2010) encouraged screening but mainly for those already insured. The United States Preventive Services Task Force 2009 guidelines recommended against screening those 40 to 49 years old and have left women over 74 years of age vulnerable to coverage loss. Other populations for whom significant gaps in risk information or screening use exist, including women of lower socioeconomic status, black women, men at higher than average risk of breast cancer, and sexual and gender minorities. Further work is needed to achieve higher rates of screening acceptance for all appropriate individuals so that the full mortality and treatment benefits of mammography screening can be realized.

Lebwohl, M.G., Leonardi, C.L., Mehta, N.N., Gottlieb, A.B., Mendelsohn, A.M., Parno, J., Rozzo, S.J. and Menter, M.A. (2020). “Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: Long-term results from two phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2).” J Am Acad Dermatol Sep 19;S0190-9622(20)32637-2. [Epub ahead of print.].
Menter1

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BACKGROUND: Data for the effect of metabolic syndrome (MetS) on efficacy and safety of biologic agents for psoriasis treatment are limited. OBJECTIVE: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status. METHODS: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331; NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg. RESULTS: Of 338 (n = 124/214) and 307 (n = 147/160) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of Psoriasis Area and Severity Index (PASI) 75 responders in reSURFACE 1/2 were generally comparable in patients with vs without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for PASI 90/100 responders. Tildrakizumab’s safety profile did not vary by MetS status. LIMITATIONS: Small sample size and post hoc analysis limit interpretation. CONCLUSION: Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.