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221 citation(s) found for "Hahn, L".

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation
Lee, Joo Myung , Choi, Ki Hong, Choi, Jin‐Oh , Shin, Doosup , Park, Yoonjee , Kim, Juwon, Lee, Seung Hun , Kim, Darae, Yang, Jeong Hoon, Cho, Yang Hyun, Sung, Kiick, Choi, Ji Yeon, Park, Meesoon, Kim, Jung-Sun, Park, Taek Kyu, Gwon, Hyeon-Cheol , Oh, Jae K., Jeon, Eun-Seok, Song, Young Bin , Hahn, Joo‐Yong , Choi, Seung-Hyuk , Gwon, Hyeon-Cheol , Shin, Doosup , Lee, Joo Myung , Choi, Ki Hong, Choi, Jin-Oh , Park, Yoonjee , Kim, Juwon, Lee, Seung Hun , Kim, Darae, Yang, Jeong Hoon, Cho, Yang Hyun, Sung, Kiick, Choi, Ji Yeon, Park, Meesoon, Kim, Jung-Sun, Park, Taek Kyu, Oh, Jae K., Jeon, Eun-Seok

Circulation | September 3, 2021 | Volume: 144 | Issue: 18 | Pages: 1459-1472

10.1161/circulationaha.121.056158 | PMID 34474597 Get It

Background: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. Methods: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. Results: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P =0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04–1.34], P =0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6–65.7], P <0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P <0.001; net reclassification index 1.05, P <0.001; integrated discrimination index 0.20, P <0.001). Conclusions: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02798731.
MASS-FIX versus standard methods to predict for PFS and OS among multiple myeloma patients participating on the STAMINA trial.
Krishnan, Amrita , Arendt, Bonnie K., Dasari, Surendra , Efebera, Yvonne A. , Geller, Nancy L. , Hahn, Theresa , Kohlhagen, Mindy , Landau, Heather , Pasquini, Marcelo C. , Qazilbash, Muzaffar H. , Shah, Nina , Vesole, David H. , Wallace, Paul K. , Stadtmauer, Edward A. , Murray, David , Dispenzieri, Angela , Giralt, Sergio , Hari, Parameswaran , McCarthy, Philip L. , Vogl, Dan T.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 8009-8009

10.1200/jco.2021.39.15_suppl.8009 Get It

8009 Background: Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses have been associated with better progression free survival (PFS) and overall survival (OS). Serum (SIFE) and urine immunofixation are the currently used markers for biochemical documentation of CR after which marrow is tested for plasma cell clearance. Next generation flow cytometry and sequencing are used to document the presence of minimal residual disease (MRD). Mass spectrometry of blood by MALDI (Mass-Fix) is a new simple, inexpensive, sensitive, and specific means of detecting monoclonal immunoglobulins. To better test the hypothesis that Mass-Fix is superior to existing methodologies to predict for survival outcomes—especially SIFE-- samples from the STAMINA trial (NCT01109004), a trial comparing 3 transplant approaches among patients who have already received induction, were employed. Methods: Five-hundred and seventy-five patients were included. Samples from enrollment post-induction (post-I) and 1-year post enrollment (1YR) were tested when available. Four response parameters were assessed univariately: Mass-Fix, SIFE, complete response, and MRD by next generation flow cytometry. Mass spectrometry spectra were evaluated in a blinded fashion. Complete response was according to the 2006 International Myeloma Working Group criteria. Multivariate Cox proportional hazard models using stepwise regression were developed to explore the independent effect of the different response parameters on PFS and OS and interactions with other risk factors. Results: Of the 4 response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses (Table). Of the 4 post-I measurements, only MRD predicted for PFS; however, Mass-Fix was the only post-I measurement to predict for OS. Of all the 1-year measures, both 1YR Mass-Fix and 1YR MRD positivity predicted for inferior PFS and OS. In models including MRD and Mass-Fix, SIFE and CR were not prognostic for PFS or OS. Conclusions: Mass-Fix is a powerful means to track monoclonal proteins. The full utility of Mass-Fix was not exploited given the absence of a diagnostic sample and the fact that only serum (and not urine) was tested. Despite these limitations, it performed well at pre-induction and at 1 year. Mass-Fix provides a convenient and non-invasive means of predicting for myeloma outcomes. Clinical trial information: NCT01109004. [Table: see text]
Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance)
Ballman, Karla A., Halabi, Susan , Atherton, Pamela J., Mortazavi, Amir , Sweeney, Christopher J. , Stadler, Walter M. , Teply, Benjamin A. , Picus, Joel , Tagawa, Scott T. , Katragadda, Sreedhar , Vaena, Daniel A. , Misleh, Jamal , Flaig, Thomas W. , Bajorin, Dean F. , Hahn, Olwen, Rosenberg, Jonathan E , Halabi, Susan , Mortazavi, Amir , Sweeney, Christopher , Stadler, Walter M , Teply, Benjamin A , Picus, Joel , Tagawa, Scott T , Hoimes, Christopher , Flaig, Thomas W , Bajorin, Dean , Morris, Michael J , Ballman, Karla A., Atherton, Pamela J., Plimack, Elizabeth R. , Dreicer, Robert , Small, Eric J. , Morris, Michael J.

Journal of Clinical Oncology | May 14, 2021 | Volume: 39 | Issue: 22 | Pages: 2486-2496

10.1200/jco.21.00286 | PMID 33989025 Get It

PURPOSE The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP). PATIENTS AND METHODS Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity. RESULTS With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm. CONCLUSION The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.
Real world outcomes using 20 mm balloon expandable SAPIEN 3/ultra valves compared to larger valves (23, 26, and 29 mm)–a propensity matched analysis
Eng, Marvin H. , Abbas, Amr E. , Wang, Dee Dee , Eleid, Mackram F. , Wang, Dee Dee , Eleid, Mackram F , Hahn, Rebecca T , Lee, James , O’Neill, William W.

Catheterization and Cardiovascular Interventions | May 13, 2021 | Volume: 98 | Issue: 6 | Pages: 1185-1192

10.1002/ccd.29756 | PMID 33984182 Get It

AbstractObjective/BackgroundSmall balloon expandable valves have higher echocardiographic transvalvular gradients and rates of prosthesis‐patient mismatch (PPM) compared to larger valves. However, the impact of these echocardiographic findings on clinical outcomes is unknown. We sought to determine the clinical outcomes of 20 mm SAPIEN 3 (S3 BEV) compared to larger S3 BEV in relation to echocardiographic hemodynamics.MethodsUsing the STS/ACC transcatheter valve registry, we performed a propensity‐matched comparison of patients undergoing treatment of native aortic valve stenosis using transfemoral, balloon‐expandable implantation of 20 mm and ≥ 23 mm S3 BEVs. Baseline and procedure characteristics, echocardiographic variables and survival were analyzed. Multivariable logistic regression was used to identify predictors of 1‐year mortality.ResultsAfter propensity matching of the 20 mm and ≥ 23 mm SAPIEN 3 valves, 3,931 pairs with comparable baseline characteristics were identified. Small valves were associated with significantly higher echocardiographic gradients at discharge (15.7 ± 7.1 mmHg vs. 11.7 ± 5.5 mmHg, p < 0.0001) and severe PPM rates (21.5% vs. 9.7%, p < 0.0001). There was no significant difference in 1‐year all‐cause mortality (20 mm: 13.0% vs. ≥23 mm: 12.7%, p = 0.72) or other major adverse event rates and outcomes between the two cohorts. Based on a multivariable analysis, elevated discharge mean gradient (>20 mmHg), severe PPM and the use of 20 mm versus ≥23 mm were not independent predictors of 1‐year mortality.ConclusionSAPIEN 3 20 mm valves were associated with higher echocardiographic gradients, and severe PPM rates compared to larger valves but these factors were not associated with significant differences in 1‐year all‐cause mortality or rehospitalization.
Financial Burden and Patient-Reported Outcomes after Hematopoietic Cell Transplantation: Impact of Pre-Treatment Awareness of Transplant-Associated Costs
Coronado, Diana Y. Salas, Hahn, Theresa , Albelda, Randy , Khera, Nandita , Odejide, Oreofe O. , Soiffer, Robert J. , Abel, Gregory A. , Zafar, S. Yousuf

Blood | April 6, 2021 | Volume: 130 | Issue: Suppl_1 | Pages: 684-684

10.1182/blood.v130.suppl_1.684.684 Get It

Abstract Background: Financial burden during cancer treatment is associated with compromised patient-reported outcomes (PROs). Being aware of impending costs may help preserve affected PROs during treatment, as patients can adjust their financial expectations. We aimed to determine if the relationship between financial burden and PROs differs among those who were aware versus unaware of transplant-related costs before hematopoietic cell transplantation (HCT) for hematologic malignancy. Methods: In 2015, we administered a mailed survey to adult patients at least 150 days after autologous or allogeneic HCT at three centers: Dana-Farber Cancer Institute, Roswell Park Cancer Institute, and Mayo Clinic Arizona. We assessed pre-treatment awareness of transplant-related costs, decreased household income after HCT, and financial hardship (defined as any one or two of the following: reporting being either unsatisfied with present finances, having difficulty meeting monthly bill payments, or not having enough money at the end of the month; given that experiencing all three would represent extreme hardship likely to impact PROs regardless of awareness, we excluded this group). A seven-point scale was provided for perceptions of overall quality of life (QOL, and patient-reported stress was measured with the Perceived Stress Scale (PSS-4). We fit regression models-stratified by awareness-to assess for the association of income decline and financial hardship with QOL below the median and perceived stress above the median (adjusting for transplant type, sex, age, race, marital status, income, distance to transplant center, and time since diagnosis). Results:In the overall survey cohort (n=325; response rate = 65.1%), 21.6% reported being unaware of HCT-related costs, with no differences due to age, race, income, or education as compared to those who were aware. Patients who reported being aware prior to transplant most often reported being informed of costs by a social worker (40.6%) and least often by a physician (23.4%; sources not mutually exclusive). Among aware patients, income decline after HCT was not associated with QOL below the median (AOR 1.4 [0.8, 2.5]; p=0.24); in contrast, among the unaware, income decline increased the odds of reporting worse QOL (AOR 4.3 [1.1, 16.7]; p=0.04). Among the aware, self-reported financial hardship was associated with worse QOL after HCT (AOR 2.7 [1.5, 4.8]; p=&lt;.001), but the odds were even higher among the unaware (AOR 4.7 [1.2, 19.4]; p=0.03). Similar increases were observed among the unaware for the association of decline in income and financial hardship with increased perceived stress. Conclusions: In this large multi-institutional cohort of patients post-HCT, more than one-fifth reported being unaware of transplant-related costs before the procedure. Moreover, this analysis suggests that pre-treatment awareness of transplant-related costs may ameliorate the impact of post-HCT financial burden on patient-reported outcomes. Figure Figure. Disclosures Khera: Novartis: Consultancy. Zafar: Novartis: Other: Spouse's Employment.
Baseline Testosterone Levels in Men with Clinically Localized High-Risk Prostate Cancer Treated with Radical Prostatectomy with or without Neoadjuvant Chemohormonal Therapy (Alliance)
Eastham, James A., Hahn, Olwen, Parsons, J. Kellogg , Mohler, James L. , Hillman, David W. , Heller, Glenn , Small, Eric J. , Morris, Michael J.

Journal of Urology | March 29, 2021 | Volume: 206 | Issue: 2 | Pages: 319-324

10.1097/ju.0000000000001716 | PMID 33780276 Get It

Surgical and Transcatheter Mitral Valve Replacement in Mitral Annular Calcification: A Systematic Review
Alexis, Sophia L. , Malik, Aaqib H. , El‐Eshmawi, Ahmed, George, Isaac , Sengupta, Aditya , Kodali, Susheel , Hahn, Rebecca T. , Khalique, Omar , Zaid, Syed , Bapat, Vinayak , Leon, Martin B. , Tang, Gilbert H.L. , Hahn, Rebecca T , Guerrero, Mayra , Adams, David

Journal of the American Heart Association | March 17, 2021 | Volume: 10 | Issue: 7 | Pages: No page available

10.1161/jaha.120.018514 | PMID 33728929 Get It

Abstract Mitral annular calcification with mitral valve disease is a challenging problem that could necessitate surgical mitral valve replacement (SMVR). Transcatheter mitral valve replacement (TMVR) is emerging as a feasible alternative in high‐risk patients with appropriate anatomy. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to December 25, 2019 for studies discussing SMVR or TMVR in patients with mitral annular calcification; 27 of 1539 articles were selected for final review. TMVR was used in 15 studies. Relevant data were available on 82 patients who underwent hybrid transatrial TMVR, and 354 patients who underwent transapical or transseptal TMVR. Outcomes on SMVR were generally reported as small case series (447 patients from 11 studies); however, 1 large study recently reported outcomes in 9551 patients. Patients who underwent TMVR had a shorter median follow‐up of 9 to 12 months (range, in‐hospital‒19 months) compared with patients with SMVR (54 months; range, in‐hospital‒120 months). Overall, those undergoing TMVR were older and had higher Society of Thoracic Surgeons risk scores. SMVR showed a wide range of early (0%–27%; median 6.3%) and long‐term mortality (0%–65%; median at 1 year, 15.8%; 5 years, 38.8%, 10 years, 62.4%). The median in‐hospital, 30‐day, and 1‐year mortality rates were 16.7%, 22.7%, and 43%, respectively, for transseptal/transapical TMVR, and 9.5%, 20.0%, and 40%, respectively, for transatrial TMVR. Mitral annular calcification is a complex disease and TMVR, with a versatile option of transatrial approach in patients with challenging anatomy, offers a promising alternative to SMVR in high‐risk patients. However, further studies are needed to improve technology, patient selection, operative expertise, and long‐term outcomes.
INTACT (S/N1806) phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle-invasive bladder cancer: Safety update on first 73 patients.
Jhavar, Sameer , Hahn, Noah M. , Costello, Brian A. , Tripathi, Abhishek , Gills, Jessie, Jani, Ashesh B. , Bangs, Rick , Plets, Melissa , Feng, Felix Y. , Singh, Parminder Pal , Efstathiou, Jason A. , Tangen, Catherine M. , Delacroix, Scott Edward , Sachdev, Sean , Vogelzang, Nicholas J. , Thompson, Ian M. , Lerner, Seth P.

Journal of Clinical Oncology | March 2, 2021 | Volume: 39 | Issue: 6_suppl | Pages: 428-428

10.1200/jco.2021.39.6_suppl.428 Get It

428 Background: Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation(CRT) is a standard of care for select patients with muscle invasive bladder cancer (MIBC). This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). At the time of SWOG fall 2020 DSMC report deadline we had enrolled 84 patients but data on only 73 patients were available. The same data are being submitted to ASCO GU meeting. Methods: This trial is testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with CRT vs. CRT alone in 475 patients with MIBC T2-T4aN0M0 disease. Patients are stratified based on PS; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response. Patients are followed for 5 years for recurrence or survival. This trial was not preceded by a phase I study but was designed with a safety run in of 80 patients. Study team agreed on the study design based on available data from other tumor types and initial experience from investigators running smaller similar trials. It was pre-specified that if we observe more than 25% patients having grade 3-5 colitis or cystitis in the atezo arm or any other toxicity which is deemed clinically significant and related to atezo, the trial investigators and DSMC would consider stopping further enrollment. Results: 36 patients were enrolled on the TMT alone arm and 37 patients on the TMT + atezo arm. No grade 3 or higher colitis was reported in the atezo arm. Only one patient had treatment related grade 3 radiation cystitis which was diagnosed after finishing atezo treatment. No steroids were given. Overall 23 grade 3 or higher toxicity events were reported in the atezo arm vs 11 in non- atezo arm. Most common toxicity was hematological which was considered non-immune related. None of the grade 3 or higher toxicities were considered to be immune related by the treating investigator. Conclusions: There is no evidence of increased immune related grade 3-5 AEs.DSMC has recommended to continue enrollment. Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed Clinical trial information: NCT03775265 . [Table: see text]
Abstract PD2-10: Validation of a predictive model for potential response to neoadjuvant endocrine therapy (NET) in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC): An ALTERNAT
Leitch, A. Marilyn , Sanati, Souzan , Unzeitig, Gary, Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Maluf, Horacio , Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Dockter, Travis , Zujewski, Jo Anne , Weiss, Anna , Hudis, Clifford A. , Cynthia, X. , Ellis, Matthew J. , Suman, Vera J. , Vij, Kiran R , Hoog, Jeremy , Watson, Mark A. , Dowsett, Mitch , Hieken, Tina J. , Wang, Yang , Winer, Eric P. , Hunt, Kelly K. , Partridge, Ann H. , Carey, Lisa A.

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PD2-10-PD2-10

10.1158/1538-7445.sabcs20-pd2-10 Get It

Abstract Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promote breast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NET utility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effective treatments. Dowsett et al. recently demonstrated that baseline levels of ER, progesterone receptor (PR), Ki67 (&gt;15% vs ≤15%), and Ki67 (&gt;10% vs ≤10%) 2-4 weeks (wks) after starting NET may improve appropriate patient (pt) selection for NET (PMC7280290). The ER, PR and Ki67-based prediction model divides pts with primary ER+/HER2- BC into 3 groups for appropriateness for NET: (Group 1) NET is likely to be inappropriate (Allred ER &lt;6 or ER 6 and PgR &lt;6), (Group 2) NET may be appropriate and a biopsy for on-treatment Ki67 analysis may be considered after 2-4 wks of NET (2A: ER 7 or 8 and PgR &lt;6 and 2B: ER 6 or 7 and PgR ≥6) given that on-treatment Ki67 &gt;10% has been associated with worse outcome (PMC5455353), or (Group 3) NET is appropriate (ER 8 and PgR ≥6). The ALTERNATE trial (NCT01953588) randomized postmenopausal women with clinical stage II or III, ER+ (Allred score 6-8)/HER2- BC to receive anastrozole (ANA), fulvestrant (FUL), or ANA + FUL for 6 months, unless Ki67 was &gt;10% on wk 4 or 12 biopsy, in which case pts were triaged to receive neoadjuvant chemotherapy (NCT) or surgery. As previously reported, the ET-sensitive disease (mPEPI 0 plus pCR) rates were similar across the treatment arms and overall 22% (286 of 1,299) pts had Ki67 &gt;10% at wk 4 or 12. The ALTERNATE trial therefore provides a large independent data set to evaluate the NET appropriateness model. Results: Among 1,299 eligible pts randomized to receive 6 months of NET, 214 were excluded due to absent HR Allred score (n=41) or absence of pre-treatment and wk 4 Ki67 determinations (n=173). The proportions of the remaining 1,085 pts in Group 1, 2 and 3 were 1% (n=10), 43% (n= 468), and 56% (n=607), respectively. On-study Ki67 &gt;10% prompting conversion from NET to NCT/Surgery occurred in: Group 1 90% (9 of 10), Group 2 30% (141 of 468), and Group 3 17% (104 of 607) (Table 1). Among the 1,075 pts in Groups 2 and 3, 260 (24%) pts had Ki67 ≤15% at baseline (BL), among whom only 14 (5.4%) had Ki67 &gt;10% at wk 4, compared to 231 of the 815 (28.3%) who had BL Ki67 &gt;15% and subsequent Ki67 &gt;10% at wk 4. 2% of pts who remained on NET due to on-treatment Ki67 &lt;10% had PD. Response and PEPI-0 rates by group will be reported. Conclusion: ALTERNATE trial data support a model whereby levels of ER, PR and Ki67 at diagnosis can be used for the identification of postmenopausal pts with primary ER+/HER2- BC who are appropriate for NET. When baseline ER Allred scores are &gt;6 and Ki67 ≤15%, there is a low likelihood of ET-resistant disease. When BL Ki67 is &gt;15%, ET sensitivity is variable, and on-treatment biopsy for Ki67 may assist in triaging regarding NET appropriateness, particularly given the extremely low local PD rates seen in ALTERNATE when on-treatment Ki67 was &lt;10%. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org; Clinical Trials.gov Identifier: NCT01953588 Table 1 Baseline levels of ER, PR, and Ki67 in Relation to Wk 4 Ki67 (N=1,085)BaselineWeek 4GroupNERAllred ScorePRAllred ScoreKi67Ki67 ≤10%N (%)Ki67 &gt;10%N (%)1N=26&lt;6≤15%0 (0%)2 (100%)9 (90)N=86&lt;6&gt;15%1 (12.5%)7 (87.5%)2AN=647 or 8&lt;6≤15%61 (95.3%)3 (4.7%)90 (30.1)N=2357 or 8&lt;6&gt;15%148 (63%)87 (37%)2BN=466 or 7≥6≤15%42 (91.3%)4 (8.7%)51 (30.2)N=1236 or 7≥6&gt;15%76 (61.8%)47 (38.2%)3N=1508≥6≤15%143 (95.3%)7 (4.7%)104 (17.1)N=4578≥6&gt;15%360 (78.8%)97 (21.2%) Citation Format: Matthew J Ellis, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Mitch Dowsett, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Clifford Hudis, Eric P Winer, Kelly Hunt, Ann H Partridge, Cynthia X Ma, Lisa A Carey. Validation of a predictive model for potential response to neoadjuvant endocrine therapy (NET) in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC): An ALTERNATE trial analysis (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-10.
Abstract GS4-05: Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Allianc
Cynthia, X. , Leitch, A. Marilyn , Sanati, Souzan , Unzeitig, Gary, Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Maluf, Horacio , Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Dockter, Travis , Zujewski, Jo Anne , Weiss, Anna , Hudis, Clifford A. , Suman, Vera J. , Vij, Kiran R , Hoog, Jeremy , Watson, Mark A. , Hieken, Tina J. , Wang, Yang , Hunt, Kelly K. , Winer, Eric P. , Ellis, Matthew J. , Carey, Lisa A. , Partridge, Ann H.

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: GS4-05-GS4-05

10.1158/1538-7445.sabcs20-gs4-05 Get It

Abstract Background: Ki67 values &gt;10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 &gt;10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 &gt;10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 &gt;10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were &gt;10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-05.