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Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul L. Nguyen, Clair J. Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony V. D’Amico, and Jason A. Efstathiou

NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.

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Laura Spring, Rachel Greenup, Andrzej Niemierko, Lidia Schapira, Stephanie Haddad, Rachel Jimenez, Suzanne Coopey, Alphonse Taghian, Kevin S. Hughes, Steven J. Isakoff, Leif W. Ellisen, Barbara L. Smith, Michelle Specht, Beverly Moy, and Aditya Bardia

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II–III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P<.01), and the OS rate was 95% versus 75%, respectively (P<.01). Among patients with pCR, no difference was seen in OS irrespective of baseline clinical stage (P=.6), but among patients with residual disease after NAC, a significant difference in OS based on baseline clinical stage was observed (P<.001). Conclusions: Our results suggest pCR after NAC is strongly associated with significantly improved DFS and OS in young women with breast cancer, and perhaps even more so than baseline stage. However, the significantly higher mortality for patients who did not attain pCR highlights the need for better therapies, and the neoadjuvant trial design could potentially serve as an efficient method for rapid triage and escalation/de-escalation of therapies to improve outcomes for young women with breast cancer.

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Seth A. Wander, Hyo S. Han, Mark L. Zangardi, Andrzej Niemierko, Veronica Mariotti, Leslie S.L. Kim, Jing Xi, Apurva Pandey, Siobhan Dunne, Azadeh Nasrazadani, Avinash Kambadakone, Casey Stein, Maxwell R. Lloyd, Megan Yuen, Laura M. Spring, Dejan Juric, Irene Kuter, Ioannis Sanidas, Beverly Moy, Therese Mulvey, Neelima Vidula, Nicholas J. Dyson, Leif W. Ellisen, Steven Isakoff, Nikhil Wagle, Adam Brufsky, Kevin Kalinsky, Cynthia X. Ma, Joyce O’Shaughnessy, and Aditya Bardia

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.