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Albain, Kathy S.

https://orcid.org/0000-0002-2899-2473

Mayo Clinic

Loyola University Chicago

Citations 78

Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney, Sara M. , Tayob, Nabihah , Dang, Chau T. , Isakoff, Steven J. , Valero, Vicente , Faggen, Meredith, Mulvey, Therese M. , Bose, Ron , Hu, Jiani , Weckstein, Douglas, Reeder‐Hayes, Katherine E. , Rugo, Hope S. , Ramaswamy, Bhuvaneswari , Zuckerman, Dan Sayam , Hart, Lowell L., Gadi, Vijayakrishna K. , Constantine, Michael, Cheng, Kit , Briccetti, Frederick , Schneider, Bryan P. , Garrett, Audrey Merrill, Marcom, Kelly, Albain, Kathy S. , DeFusco, Patricia, Ardman, Blair, Nanda, Rita , Jankowitz, Rachel C. , Rimawi, Mothaffar F. , Abramson, Vandana G. , Pohlmann, Paula R. , Poznak, Catherine Van , Forero‐Torres, Andres , Liu, Minetta C. , Ruddy, Kathryn J. , Rosenberg, Shoshana M. , Gelber, Richard D. , Trippa, Lorenzo , Barry, William T., DeMeo, Michelle K. , Burstein, Harold J. , Krop, Ian E. , Isakoff, Steven J , Mulvey, Therese Marie , Bose, Ron , Wolff, Antonio C , Reeder-Hayes, Katherine , Rugo, Hope S , Zuckerman, Dan , Gadi, Vijayakrishna K , Cheng, Kit , Briccetti, Frederick , Schneider, Bryan , Marcom, Paul Kelly , Albain, Kathy , Tung, Nadine , Nanda, Rita , Jankowitz, Rachel C , Rimawi, Mothaffar , Abramson, Vandana G , Van Poznak, Catherine , Forero-Torres, Andres , Liu, Minetta , Ruddy, Kathryn J , Zheng, Yue , Rosenberg, Shoshana , Trippa, Lorenzo , Partridge, Ann H , Winer, Eric , Krop, Ian E , Pohlmann, Paula , Yardley, Denise Aysel , Wolff, Antonio C. , Tung, Nadine , Zheng, Yue , Partridge, Ann H. , Winer, Eric P.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 21 | Pages: 2375-2385

10.1200/jco.20.03398 Get It

PURPOSE The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). METHODS Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.
Evaluation of intra-tumoral (IT) SD-101 and pembrolizumab (Pb) in combination with paclitaxel (P) followed by AC in high-risk HER2-negative (HER2-) stage II/III breast cancer: Results from the I-SPY 2 trial.
Chien, A. Jo , Ewing, Cheryl Ann, Campbell, Michael J. , Albain, Kathy S. , Stringer-Reasor, Erica , Church, An , Clark, Amy S. , Nanda, Rita, Berry, Donald A. , Soliman, Hatem Hussein , Boughey, Judy C. , Rugo, Hope S. , Wallace, Anne M. , Kalinsky, Kevin M. , Elias, Anthony , Mitri, Zahi Ibrahim , Thomas, Alexandra , Yau, Christina , Esserman, Laura J.

Journal of Clinical Oncology | June 1, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 508-508

10.1200/jco.2021.39.15_suppl.508 Get It

508 Background: I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. SD-101 is an investigational Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide that stimulates the production of IFN-α and interleukin (IL)-12, functional maturation of plasmacytoid dendritic cells, and production of cytotoxic antibodies. IT SD-101 was combined with systemic anti-PD-1 antibody Pb to investigate the antitumor and immunologic activity of this novel immunotherapeutic strategy. Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only pts (pts) with HER2- disease were eligible for this treatment. Treatment included weekly P x 12 in combination with IT SD-101 2 mg/ml (1 ml for T2 tumors, 2 ml for >T3 tumors) weekly x 4, then q3 weeks x 2, and IV Pb q3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) q2-3 weeks x 4 (SD-101+Pembro 4). Pts in the control arm received weekly P x 12 followed by AC q2-3 weeks x 4. The I-SPY 2 methods have been previously published. This investigational arm was eligible for graduation (>85% chance of success in a 300-person phase 3 neoadjuvant trial) in 3 of 10 pre-defined signatures: HER2-, hormone receptor (HR)+/HER2- and HR-/HER2-. Results: 75 pts were randomized and evaluable in SD-101+Pembro 4 treatment arm. The control arm included 329 historical controls enrolled since April 2010. The study arm was stopped due to maximal patient accrual. Pt characteristics were balanced; 56% HR+, 44% HR-. The probability that SD-101+Pembro4 was superior to control exceeded 97% for all eligible tumor signatures, but did not reach the threshold for graduation in any of the signatures. However, it is notable that the rate of pCR/Residual Cancer Burden 1 (RCB1) in the HR+/HER2- signature was 51%. Preliminary safety events for SD-101+Pembro 4 include increased rates of fever, neutropenia, febrile neutropenia, transaminitis, and immune-related events, including adrenal insufficiency. Conclusions: The SD-101+Pembro 4 regimen was active but did not meet the pre-specified threshold for graduation in I-SPY 2. pCR/RCB 1 analysis suggests improved response in the HR+/HER-negative signature compared to control. The clinical significance of these findings needs to be weighed against the potential risk of immune-related toxicities. Clinical trial information: NCT01042379. [Table: see text]
Abstract PD1-10: Evaluation of SGN-LIV1a followed by AC in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL
Beckwith, Heather , Schwab, Richard J. , Stringer-Reasor, Erica , Wei, Shi , Chien, A. Jo , Albain, Kathy S. , Clark, Amy S. , Han, Heather, Nanda, Rita, Sanft, Tara , Perlmutter, Jane , Melisko, Michelle , Veer, Laura J. van’t , Wilson, Amy , Asare, Smita , Sanil, Ashish, Berry, Donald A. , Schwab, Richard, Yau, Christina , Kalinsky, Kevin M. , Wallace, Anne M. , Elias, Anthony , Yee, Douglas , Boughey, Judy C. , Isaacs, Claudine , Mitri, Zahi Ibrahim , Lang, Julie E. , Thomas, Alexandra , DeMichele, Angela , Rugo, Hope S. , Hylton, Nola M. , Symmans, W. Fraser , Esserman, Laura J.

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PD1-10-PD1-10

10.1158/1538-7445.sabcs20-pd1-10 Get It

Abstract Background: I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk stage II/III breast cancer. The primary endpoint is pathologic complete response (pCR, ypT0/Tis ypN0). SGN-LIV1A is an investigational antibody drug conjugate consisting of an antibody to LIV1A, a zinc transporter highly prevalent in breast cancer, and a highly potent microtubule inhibitor, monomethyl auristatin E. Retrospective IHC analysis of LIV1A expression levels amongst tumor samples from 100 previous ISPY-2 patients showed 88% of breast tumor samples with moderate to high expression of LIV1A (Yau, C. et al SABCS 2018).Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only HER2 negative (HER2-) patients were eligible for this treatment, hormone-receptor positive (HR+) patients had to have MP high molecular profile. Treatment included SGN-LIV1A 2.5 mg/kg (max dose 250 mg) every 3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) every 2-3 weeks x 4. The control arm was weekly paclitaxel x 12 followed by AC every 2-3 weeks x 4. All patients undergo serial MR imaging where response at 3 & 12 weeks combined with accumulating pCR data are used to estimate, and continuously update, predicted pCR rate for the trial arm. Analysis set was modified intention to treat with patients who switched to non-protocol therapy counted as non-pCR and not as their pCR status at time of surgery. The goal is to identify/graduate regimens with ≥85% Bayesian predictive probability of success (i.e. demonstrating superiority to control) in a future 300-patient phase 3 neoadjuvant trial with a pCR endpoint within signatures defined by HR & HER2 status & MP result. This investigational arm was eligible for graduation in 3 of 10 pre-defined signatures: HER2-, HR+HER2- and HR-HER2-. Regimens may also leave the trial for futility (&lt; 10% probability of success), maximum sample size accrual (10% &lt; probability of success &lt;85%), maximum time in trial (2 years) or for safety as recommended by the independent DSMB. Results: Sixty patients were randomized and evaluable to SGN-LIV1A. The study arm was stopped due to reaching the predetermined time limit for patient accrual of 2 yrs. Final estimated pCR rates are below. The estimated pCR rates were similar between the SGN-LIV1A and control arms for any tumor subtype. Preliminary safety events for SGN-LIV1A include increased rates of transaminitis and hyperglycemia and reduced rates of peripheral neuropathy compared to control. One patient was removed from the analysis as she was determined to have angiosarcoma of the breast. Notably, this patient had a dramatic early response and subsequent pCR to SGN-LIV1A treatment. Conclusion: The value of I-SPY 2 is to give insight about the performance of an investigational agent’s likelihood of achieving pCR. SGN-LIV1A delivered every 3 weeks was comparable to paclitaxel for the primary endpoint of pCR in I-SPY2 and may have a similar side effect profile, however, with less peripheral neuropathy. Clinical trials evaluating weekly dosing of SGN-LIV1A are ongoing. A trial of SGN-LIV1A in the treatment of angiosarcoma is under consideration at this time. Final Estimated pCR Rates and Predictive ProbabilitiesEstimated pCR rate(95% prob interval)SignatureSGN-LIV1AControlProbability SGNLIV1A Superior to ControlPredictive Probability of Success in Phase 3HER2-0.16 (0.08-0.24) N= 600.20 (0.16-0.25) N= 3270.180.02HR-/HER2-0.25 (0.12-0.37) N=360.28 (0.21-0.35) N=1460.310.06HR+/HER2-0.09 (0-0.18) N=240.14 (0.09-0.19) N=1810.150.03 Citation Format: Heather Beckwith, Richard Schwab, Christina Yau, Erica Stringer-Reasor, Shi Wei, A. Jo Chien, Kathy S Albain, Kevin Kalinsky, Anne Wallace, Anthony Elias, Douglas Yee, Amy S Clark, Judy C Boughey, Heather Han, Rita Nanda, Claudine Isaacs, Zahi Mitri, Julie E Lang, Alexandra Thomas, Tara Sanft, Angela DeMichele, Jane Perlmutter, Hope S Rugo, Nola M Hylton, W. Fraser Symmans, Michelle E Melisko, Laura J van't Veer, I-SPY 2 Consortium, Amy Wilson, Smita M Asare, Ashish Sanil, Donald A Berry, Laura J Esserman. Evaluation of SGN-LIV1a followed by AC in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL [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 PD1-10.
Abstract GS3-00: First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (
Albain, Kathy S. , Hayes, Daniel F. , Perez, Edith A. , Goldstein, Lori J. , Chia, Stephen , Dhesy-Thind, Subkhbinder, Rastogi, Priya , Gil, Miguel Gil, Arce-Salinas, Claudia , Pierga, Jean‐Yves , Lluch, Ana Hernandez, Vasquez, Manuel Ramos, Borrego, Manuel Ruíz, Ferrero, Jean-­Marc , Schott, Anne F. , Shak, S., Lew, Danika L., Miao, Jieling, Dhesy‐Thind, Sukhbinder , Dhesy-Thind, Sukhbinder , Kalinsky, Kevin M. , Barlow, William E. , Meric‐Bernstam, Funda , Gralow, Julie R. , Lin, Nancy U. , Alba, Emilio , Delaloge, Suzette , Martín, Miguel , Brain, Etienne G.C. , Park, In Hae , Jung, Kyung Hae , Sharma, Priyanka , Miao, Jieling , Tripathy, Debu , Hortobágyi, Gabriel N. , Pusztai, Lajos

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: GS3-00-GS3-00

10.1158/1538-7445.sabcs20-gs3-00 Get It

Abstract Funding: Supported by National Cancer Institute grants U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868, U10CA180863; and in part by Susan G. Komen for the Cure® Research Program, The Hope Foundation for Cancer Research, Breast Cancer Research Foundation, and Genomic Health, Inc. Acknowledgement: The authors wish to thank Dr. Ana M. Gonzalez-Angulo, MD, for her invaluable contributions to the design and implementation of this study. Background: The clinical utility of the RS to determine CT benefit is well established in pts with HR+, HER2-, axillary lymph node (LN)-negative BC. Retrospective analyses from SWOG S8814 support the potential prognostic and predictive role of RS for CT benefit in postmenopausal pts with LN+ BC. SWOG S1007 is a prospective, randomized trial of endocrine therapy (ET) vs. chemoendocrine therapy (CET) in women with 1-3 +LN and a RS &lt; 25 (NCT01272037). Methods: Eligibility criteria included women &gt; 18 years of age with HR+, HER2- BC and 1-3 +LN and no contraindications to taxane and/or anthracycline based CT. Women with a RS &lt; 25 were randomized to receive ET or CET in 1:1 randomization using 3 stratification factors: (1) RS (0-13 vs.14-25); (2) menopausal status; and (3) axillary nodal dissection vs. sentinel node biopsy. The primary objective was to determine the effect of CT on invasive disease-free survival (IDFS) and whether the effect depended on the RS. The primary analysis was to test for a significant interaction of the treatment arm and continuous RS using a Cox regression model for IDFS, adjusting for treatment, RS, and menopausal status. A total of 832 IDFS events were expected for the final analysis. Secondary objectives included overall survival (OS). The protocol specified that interaction between treatment and the stratification variables was to be tested and, if significant, separate analyses performed by stratum. Annual interim analyses were planned starting at 24% of events. At the third interim analysis with 410 IDFS events, the Data and Safety Monitoring Committee recommended reporting results, with a decision by the NCI’s Cancer Therapy Evaluation Program, the study sponsor. Results: Of the 9,383 women screened from 2/28/11-9/29/17, 5,083 pts (54.2%) were randomized. With a median follow-up of 5.1 years, 447 IDFS events have been observed. For the primary analysis, the interaction test for CT benefit and continuous RS was not statistically significant, p=0.30. In a model with CT, RS, and menopausal status (no interaction term), higher continuous RS was associated with worse IDFS [HR 1.06, 2-sided p&lt;0.001, 95% Confidence Interval (CI) 1.04-1.07], and CT was associated with an improvement in IDFS (HR 0.81, p=0.026, 95% CI 0.67-0.98). In a pre-specified analysis, a significant interaction was identified between CT and menopausal status (p=0.004), necessitating separate analyses by menopausal status. In postmenopausal pts (N=3350, 67%), adjusting for continuous RS, the HR for CET vs. ET was not significant (HR=0.97, p=0.82, 95% CI 0.78-1.22; 5-year IDFS 91.6% vs. 91.9%) indicating no benefit from CT. In premenopausal pts (N=1665, 33%), the HR (0.54) was statistically significant (p=0.0004, 95% CI 0.38-0.76; 5-year IDFS 94.2% vs. 89.0%), indicating CT benefit. In premenopausal pts, ovarian suppression was performed in 15.9% vs. 3.7% (ET vs. CET), and 47.9% vs. 26.4% reported menstruation after 6 months of treatment. Although the number of events is limited, the HR for treatment adjusted by RS for OS in premenopausal pts was 0.47 (p=0.032, 95% CI 0.24-0.94). At this time, there is no differential effect with CT in regard to other stratification factors. Conclusions: There is a significant differential treatment effect of CT benefit based on RS for premenopausal vs. postmenopausal women requiring separate analyses. While only 54% of the protocol specified events are recorded and pts will be followed for 15 years, the current data show that adjuvant therapy can be de-escalated to ET alone in postmenopausal pts with a RS &lt; 25 and 1-3 +LN. However, there is a strong IDFS benefit for CET in premenopausal pts, with an early indication of an OS improvement. Citation Format: Kevin Kalinsky, William E Barlow, Funda Meric-Bernstam, Julie R Gralow, Kathy S Albain, Daniel Hayes, Nancy Lin, Edith A Perez, Lori J Goldstein, Stephen Chia, Subkhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Miguel Martín, Miguel Gil Gil, Claudia Arce-Salinas, Etienne Brain, In Hae Park, Jean-Yves Pierga, Ana Hernandez Lluch, Manuel Ramos Vasquez, Manuel Ruiz Borrego, Kyung Hae Jung, Jean-Marc Ferrero, Anne Schott, Steve Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Debu Tripathy, Gabriel Hortobagyi, Lajos Pusztai. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) &lt; 25: SWOG S1007 (RxPonder) [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 GS3-00.
Race, Ethnicity, and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer in the Randomized TAILORx Trial
Albain, Kathy S. , Gray, Robert J. , Makower, Della , Faghih, Amir, Hayes, Daniel F. , Dees, Elizabeth Claire , Goetz, Matthew P. , Lively, Tracy , Saphner, Thomas J. , Whelan, Timothy J. , Wood, William C., Keane, Maccon, Reddy, Pavan S. , Goggins, Timothy F., Toppmeyer, Deborah , Kaklamani, Virginia , Abrams, Jeffrey S. , Gómez, Henry , Goetz, Matthew P , Gray, Robert J , Geyer, Charles E. , Olson, John A. , Badve, Sunil , Wagner, Lynne I. , Ellis, Matthew J. , Gomez, Henry L. , Mayer, Ingrid A. , Brufsky, Adam , Berenberg, Jeffrey L. , Sledge, George W. , Sparano, Joseph A.

JNCI: Journal of the National Cancer Institute | September 19, 2020 | Volume: 113 | Issue: 4 | Pages: 390-399

10.1093/jnci/djaa148 Get It

Abstract Background Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results Of 9719 eligible women with hormone receptor–positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.
Abstract CT011: Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL
Haddad, Tufia C. , Stringer-Reasor, Erica , Chien, A. Jo , Borges, Virginia, Nanda, Rita , Albain, Kathy S. , Müller, Aixa , Kemmer, Kathleen, Clark, Amy S. , Perlmutter, Jane , Melisko, Michelle , Schwab, Richard B. , Wilson, Amy , Singhrao, Ruby , Asare, Smita , Veer, Laura J. van’t , Sanil, Ashish, Berry, Donald A. , Pusztai, Lajos , Han, Hyo S , Yau, Christina , Wolf, Denise M. , Wallace, Anne M. , Shatsky, Rebecca , Helsten, Teresa L. , Boughey, Judy C. , Falkson, Carla I. , Mukhtar, Rita A. , Elias, Anthony , Yee, Douglas , Kalinsky, Kevin M. , Isaacs, Claudine , Thomas, Alexandra , Hylton, Nola M. , Symmans, W. Fraser , Rugo, Hope S. , DeMichele, Angela , Esserman, Laura J.

Cancer Research | September 4, 2020 | Volume: 80 | Issue: 16_Supplement | Pages: CT011-CT011

10.1158/1538-7445.am2020-ct011 Get It

Abstract Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint risk to evaluate novel agents as neoadjuvant therapy for breast cancer. The primary endpoint is pathologic complete response (pCR, ypT0/is ypN0)). DNA repair deficiency in cancer cells can lead to immunogenic neoantigens, activation of the STING pathway, and PARP inhibition can also upregulate PD-L1 expression. Based on these rationales we tested the combination of durvalumab (anti-PDL1), olaparib (PARP inhibitor) and paclitaxel in I-SPY2. Methods: Women with tumors ≥ 2.5 cm were eligible for screening. Only HER2 negative (HER2-) patients were eligible for this treatment, hormone receptor positive (HR+) patients had to have MammaPrint high molecular profile. Treatment included durvalumab 1500 mg every 4 weeks x 3, olaparib 100 mg twice daily through weeks 1-11 concurrent with paclitaxel 80 mg/m2 weekly x 12 (DOP) followed by doxorubicin/cyclophosphamide (AC) x 4. The control arm was weekly paclitaxel x 12 followed by AC x 4. All patients undergo serial MRI imaging and imaging response at 3 & 12 weeks combined with accumulating pCR data are used to estimate, and continuously update, predicted pCR rate for the trial arm. Regimens “graduation with success” when the Bayesian predictive probability of success in a 300-patient phase 3 neoadjuvant trial in the appropriate biomarker groups reaches &gt; 85%. Results: A total of 73 patients received DOP treatment including 21 HR- tumors (i.e. triple-negative breast cancer, TNBC) and 52 HR+ tumors between May 2018 - June 2019. The control group included 299 patients with HER2- tumors. The DOP arm graduated in June 2019, 13 months after enrollment had started, for all HER2- negative and the HR+/HER2- cohorts with &gt; 0.85% predictive probabilities of success. 72 patient completed surgery and evaluable for pCR, the final predicted probabilities of success in a future phase III trial to demonstrate higher pCR rate with DOP compared to control are 81% for all HER2- cancers (estimated pCR rate 37%), 80% for TNBC (estimated pCR rate 47%) and 74.5% for HR+/HER2- patients (estimated pCR rate 28%). Association between pCR and germline BRCA status and immune gene expression including PDL1 will be presented at the meeting. No unexpected toxicities were seen, but 10 patients (14%) had possibly immune or olaparib related grade 2/3 AEs (3 pneumonitis, 2 adrenal insufficiency, 1 colitis, 1 pancreatitis, 2 elevated LFT, 1 skin toxicity, 2 hypothyroidism, 1 hyperthyroidism, 1 esophagitis). Conclusion: I-SPY2 demonstrated a significant improvement in pCR with durvalumab and olaparib included with paclitaxel compared to chemotherapy alone in women with stage II/III high-risk, HER2-negative breast cancer, improvement was seen in both the HR+ and TNBC subsets. Citation Format: Lajos Pusztai, Hyo S. Han, Christina Yau, Denise Wolf, Anne M. Wallace, Rebecca Shatsky, Teresa Helsten, Judy C. Boughey, Tufia Haddad, Erica Stringer-Reasor, Carla Falkson, A. Jo Chien, Rita Mukhtar, Anthony Elias, Borges Virginia, Rita Nanda, Douglas Yee, Kevin Kalinsky, Kathy S. Albain, Aixa Soyano Muller, Kathleen Kemmer, Amy S. Clark, Claudine Isaacs, Alexandra Thomas, Nola Hylton, W. Fraser Symmans, Jane Perlmutter, Michelle Melisko, Hope S. Rugo, Richard Schwab, Amy Wilson, Amy Wilson, Ruby Singhrao, Smita Asare, Laura J. van't Veer, Angela M. DeMichele, Ashish Sanil, Donald A. Berry, Laura J. Esserman, Trial Consortium I-SPY 2. Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT011.
Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer
Yee, Douglas , Symmans, W. Fraser , Albain, Kathy S. , Chen, Yunn-Yi, Krings, Gregor , Wei, Shi , Harada, Shuko , Datnow, Brian, Fadare, Oluwole , Klein, Molly, Chen, Beiyun, Adamson, Kathi, Sams, Sharon B. , Mhawech‐Fauceglia, Paulette , Magliocco, Anthony M., Feldman, Mike, Rendi, Mara H. , Sattar, Husain, Zeck, Jay , Ocal, Idris Tolgay, Tawfik, Ossama , LeBeau, Lauren, Sahoo, Sunati , Vinh, Tuyethoa N., Chien, A. Jo , Forero‐Torres, Andres , Stringer-Reasor, Erica , Ellis, Erin D. , Lu, Janice , Lang, Julie E. , Clark, Amy S. , Nanda, Rita , Northfelt, Donald W. , Khan, Qamar J. , Viscusi, Rebecca K., Euhus, David , Edmiston, Kirsten K., Kemmer, Kathleen, Park, John W., Liu, Minetta C. , Olopade, Olufunmilayo I. , Leyland‐Jones, Brian , Tripathy, Debasish , Moulder, Stacy L. , Schwab, Richard B. , Lo, Shelly S. , Beckwith, Heather , Haugen, Patricia, Veer, Laura J. van’t , Perlmutter, Jane , Melisko, Michelle , Wilson, Amy , Peterson, Garry , Buxton, Meredith , Paoloni, Melissa, Clennell, Julia L. , Hirst, Gillian L. , Singhrao, Ruby , Steeg, Katherine, Matthews, Jeffrey B. , Asare, Smita , Sanil, Ashish, Esserman, Laura J. , Berry, Donald A. , Tripathy, Debu , Ocal, Idris T, Olopade, Olufunmilayo I , Symmans, W Fraser , Esserman, Laura J , Hirst, Gillian L , Yee, Douglas , DeMichele, Angela , Yau, Christina , Isaacs, Claudine , Chen, Yunn‐Yi , Krings, Gregor, Pambuccian, Stefan E. , Wallace, Anne M. , Pusztai, Lajos , Boughey, Judy C. , Elias, Anthony , Han, Hyo S , Chui, Stephen Y., Rugo, Hope S. , Helsten, Teresa L. , Hylton, Nola M. , Asare, Adam L. , Matthews, Jeffrey B., Berry, Scott

JAMA Oncology | July 23, 2020 | Volume: 6 | Issue: 9 | Pages: 1355

10.1001/jamaoncol.2020.2535 Get It

Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx
Whelan, Timothy J. , Garcia, Sofia F. , Yanez, Betina R. , Carlos, Ruth C. , Albain, Kathy S. , Hayes, Daniel F. , Dees, Elizabeth Claire , McCaskill-Stevens, Worta J., Minasian, Lori M. , Cella, David , Garcia, Sofia F , Wagner, Lynne I. , Gray, Robert J. , Sparano, Joseph A. , Tevaarwerk, Amyé , Olson, John A. , Goetz, Matthew P. , Pritchard, Kathleen I. , Geyer, Charles E. , Sledge, George W.

Journal of Clinical Oncology | April 9, 2020 | Volume: 38 | Issue: 17 | Pages: 1875-1886

10.1200/jco.19.01866 Get It

PURPOSE Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were nonsignificant. CONCLUSION Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.
Abstract PD9-05: Lack of background parenchymal enhancement suppression in breast MRI during neoadjuvant chemotherapy may be associated with inferior treatment response in hormone receptor positive breast cancer
Newitt, David C. , Harnish, Roy, Gibbs, Jessica , Jones, Ella F. , Wilmes, Lisa J., Joe, Bonnie N. , Campbell, Michael J. , Veer, Laura J. van’t , DiMichele, Angela, Berry, Donald A. , Albain, Kathy S. , Chien, A. Jo , Clark, Amy S. , Edmiston, Kirsten K., Ellis, Erin D. , Euhus, David , Han, Heather, Khan, Qamar J. , Lu, Janice , Mitri, Zaha, Nanda, Rita, Northfelt, Donald W. , Sanft, Tara, Stringer-Reasor, Erica , Viscusi, Rebecca K., Yung, Rachel L. , Melisko, Michelle , Perlmutter, Jane , Schwab, Richard B. , Asare, Smita , Yau, Julie E., Onishi, Natsuko , Li, Wen , Nguyen, Alex , Basu, Amrita B , Yee, Douglas , Boughey, Judy C. , Elias, Anthony , Isaacs, Claudine , Lang, Julie E. , Meisel, Jane Lowe , Sanft, Tara , Wallace, Anne M. , Rugo, Hope S. , Symmans, W. Fraser , Yau, Christina , Esserman, Laura J. , Hylton, Nola M.

Cancer Research | March 26, 2020 | Volume: 80 | Issue: 4_Supplement | Pages: PD9-05-PD9-05

10.1158/1538-7445.sabcs19-pd9-05 Get It

Abstract Purpose In breast MRI, contrast enhancement of normal fibroglandular tissue is referred to as background parenchymal enhancement (BPE). Hormonal status significantly affects the degree of BPE, potentially due to the association with mammary vascularity and activity1-5. Studies have shown that BPE may be associated with breast cancer survival6, treatment response to neoadjuvant chemotherapy (NAC)7,8 and future breast cancer risk9. In most patients undergoing NAC, BPE is suppressed by the nonspecific anti-proliferative effects of chemotherapy on normal breast and/or ovary5,10. However, some patients exhibit equivalent or even stronger BPE post-NAC compared to pre-NAC. We hypothesized that non-suppressed BPE in post-NAC MRI may be associated with inferior treatment response. This study aimed to investigate the association between BPE suppression and treatment response as defined by pathologic complete response (pCR). Methods This study included patients with stage II/III breast cancer enrolled in the I-SPY 2 TRIAL being treated with standard NAC with or without investigational agents. The whole cohort was split into two subgroups based on hormone receptor status (HR+, n= 536; HR-, n=452). Patients underwent dynamic contrast enhanced MRIs at four time points during NAC: baseline (T0), after 3 weeks of the first regimen (T1), inter-regimen (T2), and pre-surgery (T3). Using in-house software, the contralateral breast parenchyma was automatically segmented for the entire breast volume. Quantitative BPE (qBPE) was calculated as the mean early (~150s post-contrast injection) percent enhancement of the central 50% of the axial slices. A breast radiologist reviewed all exams and excluded those where automated segmentation failed to accurately define tissue. For T1, T2 and T3, BPE was categorized based on the change from T0 as suppressed (qBPE &lt; qBPE[T0]) or non-suppressed (qBPE ≥ qBPE[T0]). Chi-squared test was used to examine the association between BPE suppression and pCR, with p&lt;0.05 considered statistically significant. Results HR+ cohort: pCR rates were lower for patients with non-suppressed BPE than those with suppressed BPE at every visit (T1-T3) (Table 1). The difference was statistically significant at T2 (p=0.04) and T3 (p=0.01). Table 1: HR+ cohortpCR rate (%)No. of pCR patientsNo. of non-pCR patientsTotal number of patientsP valueOverall22.8122414536BPE at T1suppressed23.6822663480.45non-suppressed20.532124156BPE at T2suppressed25.7972803770.04*non-suppressed16.01789106BPE at T3suppressed25.7982833810.01*non-suppressed12.5128496 HR- cohort: pCR rates were slightly lower for the non-suppressed BPE group, but no statistically significant association was found (Table 2). Table 2: HR- cohortpCR rate (%)No. of pCR patientsNo. of non-pCR patientsTotal number of patientsP valueOverall44.7202250452BPE at T1suppressed46.81411603010.66non-suppressed44.45265117BPE at T2suppressed48.81441512950.79non-suppressed47.3434891BPE at T3suppressed49.31461502960.94non-suppressed48.9434588 Conclusion In HR+ breast cancer, lack of BPE suppression may indicate inferior treatment response. The contrasting results in HR+ and HR- cohorts are noteworthy in terms of the possible relationship between suppression of normal mammary and ovarian activity and treatment response in HR+ cancer. Reference Radiographics 2014; 34: 234-47. Radiology 1997; 203: 137-44. Radiology 1997; 203: 145-9. Breast J 2005; 11: 236-41. AJR Am J Roentgenol 2015; 204: 669-73. Eur Radiol 2018; 28: 4705-16. Eur Radiol 2016; 26: 1590-6. Transl Oncol 2015; 8: 204-9. J Clin Oncol 2019; : JCO1800378. Radiology 2015; 277: 687-96. Citation Format: Natsuko Onishi, Wen Li, David C. Newitt, Roy Harnish, Jessica Gibbs, Ella F. Jones, Alex Nguyen, Lisa Wilmes, Bonnie N. Joe, Michael J. Campbell, Amrita Basu, Laura J. van’t Veer, Angela DiMichele, Douglas Yee, Donald A. Berry, Kathy S. Albain, Judy C. Boughey, A. Jo Chien, Amy S. Clark, Kirsten K. Edmiston, Anthony D. Elias, Erin D. Ellis, David M. Euhus, Heather S. Han, Claudine Isaacs, Qamar J. Khan, Julie E. Lang, Janice Lu, Jane L. Meisel, Zaha Mitri, Rita Nanda, Donald W. Northfelt, Tara Sanft, Erica Stringer-Reasor, Rebecca K. Viscusi, Anne M. Wallace, Rachel Yung, Michelle E. Melisko, Jane Perlmutter, Hope S. Rugo, Richard Schwab, W. Fraser Symmans, Smita M. Asare, Julie E. Yau, Christina Yau, Laura J. Esserman, Nola M. Hylton. Lack of background parenchymal enhancement suppression in breast MRI during neoadjuvant chemotherapy may be associated with inferior treatment response in hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD9-05.