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  • 1
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    Abstract P5-16-01: Assessment of health-related quality of life by clinical response from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC)
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-01-P5-16-01
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-01-P5-16-01
    Abstract: Background: In ASCENT, patients with mTNBC refractory to or relapsing after ≥2 prior chemotherapies (at least one in the metastatic setting) were randomized 1:1 to receive sacituzumab govitecan (SG) or single-agent treatment of physician’s choice (TPC) (capecitabine, eribulin, vinorelbine, or gemcitabine). Primary endpoint was progression free survival. Secondary endpoints included overall survival, objective response rate, clinical benefit rate, and safety. Here we examined whether health-related quality of life (HRQoL) differed by clinical response. Methods: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30) version 3 was used to assess HRQoL at baseline and on day 1 of each treatment cycle. This analysis included intention-to-treat patients who had a completed at least one of the 15 domains/scales at baseline and at least one evaluable assessment at post-baseline visits based on EORTC QLQ-C30. Patients were classified as responders (partial or complete disease response) or non-responders (stable or progressive disease or not evaluable) based on best overall response (RECIST). A mixed-effect model for repeated measures (MMRM) was used to estimate leastsquare (LS) mean EORTC QLQC30 score changes from baseline using all HRQoL data assessed during Cycle 2 Day 1 (C2D1) to C6D1 (where n was ≥25 in both treatment arms) for responders and nonresponders within each treatment group. Results: Mean QLQ-C30 subscale scores at baseline were similar between treatment arms. The analysis included 236 patients in the SG arm of the full trial population, of whom 82 (35%) were clinical responders; and 183 in the TPC arm, of whom 11 (6%) were clinical responders. Due to the small number of TPC responders, inferential statistical testing to compare between-group difference was not performed.Irrespective of their clinical response status, patients treated with SG showed more favorable LS mean changes than patients who received TPC in all EORTC QLQ-C30 domains, except for nausea/vomiting and diarrhea (Table). Overall, LS mean changes in EORTC QLQ-C30 scores in SG nonresponders were less favorable than those in SG responders, but more favorable than those in TPC responders and TPC nonresponders for most EORTC QLQ-C30 domains. Conclusions: The analysis demonstrates that regardless of response status, SG responders and non-responders showed a better trend in HRQoL changes than TPC. Patients who achieved a tumor response to SG may benefit most in HRQoL. Although patients treated with SG reported higher rates of diarrhea, this did not generate a negative impact on their overall quality of life or functioning. Table: Mixed effects model least-square mean EORTC QLQ-C30 score changes from baselineLeast-square mean change from baseline (95% confidence interval)SG responders(N=82)SG nonresponders(N=154)TPC responders(N=11)TPC non-responders(N=172)Global health status/QoL2.46 (-1.52, 6.43)-0.57 (-3.68, 2.54)-1.64 (-10.22, 6.95)-2.29 (-5.63, 1.05)FunctioningPhysical2.93 (-0.92, 6.79)0.22 (-2.71, 3.15)-3.47 (-11.93, 4.99)-3.75 (-6.87, -0.63)Role-0.35 (-5.74, 5.04)-3.23 (-7.45, 0.99)-8.40 (-19.93, 3.13)-7.33 (-11.88, -2.78)Emotional6.20 (2.23, 10.18)1.97 (-1.12, 5.06)4.87 (-3.70, 13.44)0.08 (-3.24, 3.40)Cognitive0.90 (-2.99, 4.79)-2.25 (-5.26, 0.76)-4.46 (-12.87, 3.95)-1.26 (-4.49, 1.98)Social2.06 (-3.50, 7.61)-3.35 (-7.65, 0.95)-5.79 (-18.29, 6.72)-4.36 (-8.99, 0.27)SymptomsFatigue0.90 (-3.49, 5.28)2.84 (-0.60, 6.29)4.15 (-5.34, 13.65)6.65 (2.93, 10.38)Nausea/vomiting4.68 (1.42, 7.95)4.03 (1.42, 6.64)1.38 (-5.53, 8.29)2.62 (-0.21, 5.45)Pain-11.40 (-16.43, -6.36)-8.57 (-12.48, -4.66)-11.99 (-22.85, -1.13)-0.24 (-4.47, 3.99)Dyspnea-7.88 (-13.09, -2.67)-1.90 (-5.93, 2.13)1.97 (-9.33, 13.27)3.86 (-0.47, 8.18)Insomnia-6.12 (-11.99, -0.26)-3.51 (-8.04, 1.02)4.83 (-7.85, 17.51)-0.98 (-5.86, 3.90)Appetite loss0.22 (-5.25, 5.70)5.45 (1.15, 9.75)8.67 (-3.05, 20.40)4.60 (-0.05, 9.26)Constipation0.93 (-4.57, 6.43)2.20 (-2.09, 6.49)3.87 (-7.96, 15.70)3.52 (-1.12, 8.16)Diarrhea16.03 (10.32, 21.74)13.65 (9.19, 18.11)2.46 (-9.88, 14.80)-1.53 (-6.34, 3.29)Financial difficulties-3.57 (-8.54, 1.39)-2.44 (-6.21, 1.34)-4.41 (-15.27, 6.46)0.61 (-3.42, 4.64)A higher score for a functional domain represents a higher or healthier level of functioning; a higher score for the global health status/QoL represents a higher overall HRQoL; but a higher score for a symptom domain represents a higher level of symptomatology or problems Citation Format: Sibylle Loibl, Sara M. Tolaney, Kevin Punie, Mafalda Oliveira, Hope S. Rugo, Aditya Bardia, Sara A. Hurvitz, Adam Brufsky, Kevin M Kalinsky, Javier Cortes, Joyce O’Shaughnessy, Lisa A. Carey, Luca Gianni, Véronique Diéras, Ling Shi, Mahdi Gharaibeh, Luciana Preger, Lee Moore, See Phan, Martine Piccart. Assessment of health-related quality of life by clinical response from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P5-16-01
    RVK:
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    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
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  • 2
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    Abstract P5-16-15: Post-progression therapy outcomes in patients (pts) from the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC)
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-15-P5-16-15
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-15-P5-16-15
    Abstract: Background: SG is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG is FDA approved for pts with mTNBC who received ≥2 prior chemotherapies (≥1 in the metastatic setting). The confirmatory phase 3 ASCENT study (NCT02574455) in pts treated in second line or greater (2L+) mTNBC demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit of SG over single-agent chemotherapy treatment of physician’s choice (median PFS: 4.8 vs 1.7 months, HR 0.43, P & lt;0.001; median OS: 11.8 vs 6.9 months, HR 0.51) in the full trial population, with a manageable safety profile. However, outcomes and patterns of subsequent therapy for pts who discontinue SG following progressive disease (PD) are not well characterized. This post hoc subgroup analysis investigates post-progression treatment and OS of pts who discontinued SG due to PD during the ASCENT trial. Methods: In ASCENT, pts with mTNBC refractory/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or progression. Post-progression outcomes were assessed in pts who discontinued SG due to progressive disease (PD). Pts were followed every 4 weeks for OS, including documentation of further therapy for breast cancer. Time to post-progression therapy was defined as the number of months from time of randomization until the initiation of subsequent anticancer therapy. OS was analyzed in pts who received post-progression therapy vs those who did not and defined as the number of months from randomization or from end of SG treatment, using Kaplan Meier estimates and Cox regression. Results: 222/267 (83%) pts who were randomized to receive SG discontinued SG due to PD. In these patients median age was 53 years (range, 27-82), median number of prior anticancer regimens was 4, and 7% had known germline BRCA1/2 mutations. Pts received SG for a median duration of 4.2 months (range, 0.0-18.7). Following SG discontinuation, post-progression therapy was received by 73% (n=163) of pts; common post-SG therapies included eribulin (n=70; 32%), carboplatin (n=34; 15%), capecitabine (n=34; 15%), and atezolizumab, (n=15; 7%). The median time to receipt of post-progression therapy was 5.4 months (range, 1.0-19.8). Median OS in pts who received any post PD treatment vs those who did not receive post PD treatment following SG was 13.4 vs 7.3 months (HR, 0.46; 95% CI, 0.32-0.67; P & lt;0.0001) from time of randomization and 7.9 vs 2.0 months (HR, 0.14; 95% CI, 0.09-0.22; P & lt;0.0001) from end of SG treatment, respectively. In pts who received eribulin, carboplatin, atezolizumab, or capecitabine, median OS was 14.1 (95% CI, 10.9-14.9), 13.6 (95% CI, 10.6-15.9), 16.5 (95% CI, 8.7 to not evaluable), and 14.9 (95% CI, 10.9-16.8) months from time of randomization and 8.4 (95% CI, 6.8-9.2), 8.9 (95% CI, 6.7-10.8), 8.6 (95% CI, 4.3 to not evaluable), and 8.9 (95% CI, 6.6-10.3) months from end of SG treatment, respectively. Conclusions: In ASCENT, the majority of pts who discontinued SG due to PD were able to receive subsequent therapy post-progression. Pts who received post PD therapy following SG had significantly improved median OS over those who did not receive further therapy. Pts who received eribulin, carboplatin, atezolizumab, or capecitabine, as post PD therapy had similar median OS. These results indicate that treatment with SG does not prevent receipt of further systemic therapy. Citation Format: Javier Cortés, Aditya Bardia, Delphine Loirat, Sara M. Tolaney, Kevin Punie, Mafalda Oliveira, Sara A. Hurvitz, Adam Brufsky, Sagar Sardesai, Kevin M Kalinsky, Tiffany Traina, Erika Hamilton, Joyce O’Shaughnessy, Véronique Diéras, Lisa A. Carey, Martine Piccart, Sibylle Loibl, Hope S. Rugo, Yanni Zhu, See Phan, Luca Gianni. Post-progression therapy outcomes in patients (pts) from the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-15.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P5-16-15
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    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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    detail.hit.zdb_id: 1432-1
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  • 3
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    Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint
    Springer Science and Business Media LLC ; 2019
    In:  npj Breast Cancer Vol. 5, No. 1 ( 2019-01-02)
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    In: npj Breast Cancer, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2019-01-02)
    Abstract: In the original version of the published article, Constantine Godellas was mistakenly omitted from the Author list and Author Contributions statement. Constantine Godellas has been added as the 29th Author, and is affiliated with Loyola University Medical Center, Maywood, IL, United States. The author contributions statement has been updated as follows: “Author Contributions Statement: Judy C. Boughey conducted the review of current protocols, led the effort to establish new I-SPY standards and was the principal author of the manuscript. Laura Esserman co-led the review and standardization processes. Michael D. Alvarado, Rachael B. Lancaster, Fraser Symmans, W, Rita Mukhtar, Jasmine Wong, Cheryl Ewing, David Potter, Todd Tuttle, Tina Hieken, Jodi Carter, James Jakub, Henry Kaplan, Claire Buchanan, Nora Jaskowiak, Husain Sattar, Jeffrey Mueller, Rita Nanda, Claudine Isaacs, Paula Pohlmann, Filipa Lynce, Eleni Tousimis, Jay Zeck, M. Catherine Lee, Julie Lang, Paulette Mhawech-Fauceglia, Roshni Rao, Bret Taback, Margaret Chen, Kevin Kalinsky, Hanina Hibshoosh, Brigid Killelea, Constantine Godellas, and Tara Sanft provided medical and scientific expertise/opinion towards the development of I-SPY standards. Jane Perlmutter provided the patient advocate’s perspective in these discussions. All I-SPY2 trial investigators participated in the review of current standards, had the opportunity to participate in and comment on proposed standards and the final manuscript. Gill Hirst and Smita Asare provided expertise on, conducted and analyzed surveys of I-SPY trial sites. Jeffrey B. Matthews provided significant input and editing throughout the manuscript development process. All authors reviewed manuscript drafts and signed off on the final manuscript. This has been corrected in the HTML and PDF version of the article.
    Type of Medium: Online Resource
    ISSN: 2374-4677
    URL: Article
    DOI: 10.1038/s41523-018-0096-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 4
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    Durvalumab With Olaparib and Paclitaxel for High-Risk HER2-Negative Stage II/III Breast Cancer: Results From the Adaptively Randomized I-SPY2 Platform Trial
    Elsevier BV ; 2020
    In:  SSRN Electronic Journal
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    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    URL: Article
    DOI: 10.2139/ssrn.3751802
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 5
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    Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint
    Springer Science and Business Media LLC ; 2018
    In:  npj Breast Cancer Vol. 4, No. 1 ( 2018-08-17)
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    In: npj Breast Cancer, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2018-08-17)
    Abstract: Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease—the primary endpoint of many drug therapy trials in the neoadjuvant setting—is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.
    Type of Medium: Online Resource
    ISSN: 2374-4677
    URL: Article
    DOI: 10.1038/s41523-018-0074-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
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  • 6
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    Abstract GS2-07: Updated results from a phase 3 randomized clinical trial in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) ≤ 25 randomized to endocrine therapy (ET) +/- chemotherapy (CT): SWOG S1007 (RxPONDER)
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. GS2-07-GS2-07
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. GS2-07-GS2-07
    Abstract: Background: We previouslyreported that invasive disease-free survival (IDFS), the primary outcome, and distantdisease-free survival (DDFS), a secondary outcome, differed by menopausalstatus in a pre-specified analysis. Here,we report updates on IDFS and DDFS with additional follow-up, as well as distantrecurrence-free interval (DRFI) and post hoc analyses in premenopausal women.Methods: Eligibilitycriteria included women & gt; 18 years of age with HR+, HER2-BC and 1-3 +LN and no contraindications to taxane and/or anthracycline basedCT. DRFI was defined as time to distant recurrence or death from breast cancer.Analyses were intent-to-treat among eligible pts. We performed a post hocanalysis evaluating IDFS between treatment arms in premenopausal pts with pN1mi.In addition, we conducted a two-year landmarked IDFS analysis by ovarianfunction suppression (OFS) or not in the ET arm, as well as by regularmenstrual periods or not in both treatment arms.Results: Among the 4,984eligible pts, there were 553 IDFS events and median follow-up of 6.1 years.Postmenopausal women do not have any IDFS or DDFS benefit with CT; however, 5-yearabsolute benefits for IDFS and DDFS with CT for premenopausal pts were 5.9% and3.3%, respectively. In pre-menopausal pts, CT was associated with improved DRFIfor all RS values & lt; 25, with an absolute improvement of 2.3% for RS0-13 and of 2.8% for RS 14-25. Among premenopausal pts, 12.4% (n=206) had pNmi)disease. In a post hoc analysis, there was a trend for CT benefit for thosewith pNmi [hazard ratio (HR)=0.44, confidence interval (CI)=0.18-1.08]. Therewere only 22 IDFS events. Only 17.2% of premenopausal pts assigned to ETunderwent OFS in the first 24 months and in two-year landmarked analysis, therewas no IDFS difference in those who underwent OFS or not (HR=0.88,CI=0.47-1.63). In premenopausal women assigned to ET, 58.9% stopped havingperiods within the first 24 months, and have anumerically improved IDFS compared to those who continued regular periods (HR=1.48,CI: 0.92-2.40). Among premenopausal assigned to CT followed by ET, 80.8%stopped having periods within the first 24 months and have a numericallyimproved IDFS compared to those who continue to have regular periods (HR=1.56, CI:0.85-2.86).Discussion: In accordancewith the differential IDFS and DDFS benefit based upon menopausal status inS1007, premenopausal pts with 1-3+LN and RS & lt; 25 had a statisticallysignificant improvement in DRFI with the addition of CT. A small proportion of S1007premenopausal participants underwent OFS. The role of OFS as it relates to CTbenefit cannot be determined from this study. A future randomized trial should address the clinical question if OFScan replace CT in premenopausal pts with HR+/HER2-, node-positive breast cancer.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. Citation Format: Kevin M Kalinsky, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori A Goldstein, Stephen KL Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Miguel Martin, Catherine M Kelly, Manuel Ruiz-Borrego, Miguel Gil-Gil, Claudia H Arce-Salinas, Etienne GC Brain, Eun Sook Lee, Jean-Yves Pierga, Begoña Bermejo, Manuel Ramos-Vasquez, Kyung Hae Jung, Jean-Marc Ferrero, Anne Schott, Steven Shak, Priyanka Sharma, Danika Lew, Jieling Miao, Debasish Tripathy, Lajos Pusztai, Gabriel Hortobagyi. Updated results from a phase 3 randomized clinical trial in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) ≤ 25 randomized to endocrine therapy (ET) +/- chemotherapy (CT): SWOG S1007 (RxPONDER) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-07.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-GS2-07
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 7
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    Abstract P1-18-37: Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 and 6i for HR+, HER2- MBC in the real world
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-18-37-P1-18-37
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P1-18-37-P1-18-37
    Abstract: Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 & 6i) provide significant benefit for patients (pts) with HR+, HER2- MBC, however, clinical questions remain regarding the optimal sequence (seq) of treatments (tx). Prior analyses of real world (rw) abemaciclib indicate up to 50% of pts have had prior palbociclib or ribociclib for MBC and published studies regarding seq and non-seq tx outcomes have had limited sample sizes. To our knowledge, the current study represents the largest rw analysis of CDK4 & 6i tx seq to date. Methods: US electronic medical records were retrospectively analyzed from the ConcertAI Oncology Dataset. Pts received abemaciclib and ≥ 1 other systemic tx line for HR+, HER2- MBC; the study period was 11/1995 (date of first MBC dx in dataset) to 10/2020 (end of follow-up). Tx sequences were identified and grouped to enable outcomes analyses. Data for 4 select groups (grp) are presented: grp 1 (1L CDK4 & 6i to 2L CDK4 & 6i), grp 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), grp 3 (2L CDK4 & 6i to 3L CDK4 & 6i), grp 4 (2L CDK4 & 6i to 3L non- CDK4 & 6i). Progression-free survival (PFS) from regimen start date to disease progression or death was analyzed by line using Kaplan-Meier method; pts were censored on the start date of the subsequent tx or end of follow-up if a progression event was not reported. Pts were characterized as having primary or secondary endocrine resistance per ESMO guidelines, if applicable. Pt characteristics at initiation of 1st CDK4 & 6i and median PFS are summarized descriptively. Results: Of 690pts, the majority were white (n=555, 80%), had a median age of 61yrs (range 26-86) and were treated in community oncology practices (80%) in southern US (47%). Most pt characteristics between grp 1 vs grp 2 were not statistically different except for pts participating in clinical trials [grp 1 (n=3; 2%) vs grp 2 (n=12; 13%)]. Pts in grp 4 were younger than grp 3, with a median age of 60 and 67yrs, respectively (p & lt;0.05). In the overall cohort, the most prevalent tx seq grp was 1L CDK4 & 6i followed by 2L CDK4 & 6i (n=165). There was significant treatment regimen heterogeneity across all grps, with the most frequent being 1L palbociclib/AI followed by 2L abemaciclib/fulvestrant received by 26 (16%) pts. Abemaciclib was prevalent in 1L (n=92; 13%), 2L (n= 204; 30%), 3L (n=122; 18%), ≥4L (n=344; 50%). Pts receiving seq CDK4 & 6i experienced a substantial PFS benefit in the subsequent line (grp 1: 17mo; grp 3: 11mo), while pts in non-seq grps experienced a numerically lower PFS from the non-CDK4 & 6i tx in the subsequent line (grp 2: 8mo; grp 4: 8mo). Median PFS for each grp is described in Table 1. Results of cox proportional hazards models will be presented. Conclusions: Seq CDK4 & 6i appears to deliver substantial 2L PFS in pts who had a meaningful PFS on 1L CDK4 & 6i. These results appear consistent for pts receiving 3L CDK4 & 6i who had a meaningful PFS to 2L CDK4 & 6i. While most pts received 1L CDK4 & 6i to 2L CDK4 & 6i, there was marked tx heterogeneity across all seqs in this predominantly community oncology sample, reinforcing the continued lack of consensus on this topic. While these results are hypothesis generating, these data serve as further rationale for additional prospective and retrospective studies evaluating the potential utilization and outcomes of CDK4 & 6i, after progression on a previous CDK4 & 6i. Table 1.Grp 11L CDK4 & 6i to 2L CDK4 & 6i n=165Grp 21L CDK4 & 6ito 2L non-CDK4 & 6i n=94Grp 32L CDK4 & 6i to 3L CDK4 & 6i n=115Grp 42L CDK4 & 6i to 3L non-CDK4 & 6i n=121Line 1No. of Events/Pts78/16572/94Median (m)18.459.8095% CI[15.0, 23.2][6.4, 14.2] Line 2No. of Events/Pts55/16540/9455/11587/121Median (m)17.308.3917.308.2995% CI[9.8, 33.4][5.9, 10.5] [12.1, 21.0][6.2, 9.9] Line 3No. of Events/Pts46/11557/121Median (m)11.227.8695% CI[6.8, 14.0][5.5, 11.3] Citation Format: Kevin M Kalinsky, Megan Kruse, Emily Nash Smyth, Claudia M Guimaraes, Santosh Gautam, Alnecia R Nisbett, Maxine D Fisher, Zhanglin Lin Cui, Lee Bowman. Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 and 6i for HR+, HER2- MBC in the real world [abstract] . In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-37.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P1-18-37
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 8
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    Abstract PD2-03: Association between co-existing genomic alterations and abemaciclib benefit in patients with metastatic hormone receptor-positive breast cancer with ESR1 mutations following disease progression on prior endocrine therapy plus palbociclib or ribociclib
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD2-03-PD2-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD2-03-PD2-03
    Abstract: Background: For patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC) and progression on combination endocrine therapy plus palbociclib/ribociclib, abemaciclib can be effective and well-tolerated, conferring durable clinical benefit in a subset of patients (Wander SA et al. JNCCN 2021). We previously reported that, even in patients with ESR1-mutant (ESR1-MUT) HR+ MBC, some - but not all - still achieve long-term disease control with abemaciclib (Wander SA et al. SABCS 2020). How to identify which patients are likely to benefit from abemaciclib after progression on combination endocrine therapy and CDK4/6 inhibition is not known and, more generally, predicting tumor response to CDK4/6 inhibition has been an area of ongoing research. Because resistance to CDK4/6 inhibition can occur through multiple mechanisms, we hypothesized that a comprehensive resistance panel, rather than single genetic markers or immunohistochemical readouts, would provide an effective predictive tool. Methods: To determine which patients with ESR1-MUT MBC and progression on endocrine therapy plus palbociclib/ribociclib benefit from abemaciclib, we examined a multicenter cohort of such patients who had genomic profiling by standard commercially available assays, the majority of which were via plasma-based cell-free DNA (cfDNA) genotyping assays. We generated a curated list based upon prior literature of CDK4/6i resistance drivers that had been validated in tumor biopsy specimens and in laboratory models: these genes were involved in cell cycle regulation (CCNE1/2, RB1, AURKA) and growth factor signaling pathways (ERBB2, FGFR1/2, AKT1, PTEN, KRAS, FAT1). Progression-free survival (PFS) was defined as time from abemaciclib initiation to time of discontinuation due to disease progression or death; patients who discontinued due to toxicity were right-censored. To examine the cellular effects of different mutations, we also studied the impact of ESR1-MUT, RB1 loss, and KRAS activation on the growth and survival (using an ATP abundance-based assay) of patient-derived circulating tumor cell (CTC) lines treated with palbociclib and abemaciclib in vitro. Results: Among patients with ESR1-MUT MBC with disease progression on endocrine therapy plus palbociclib/ribociclib (n=28), absence of co-existing genomic alterations in our curated panel was associated with greater clinical benefit with subsequent abemaciclib. Patients lacking a mutation in this resistance panel (n=17) had a median PFS of 7.0 months (95% CI: 4.1-13.2); patients with at least one mutation in this panel (n=11) had a median PFS of 3.5 months (95% CI: 2.1-5.4). The difference in PFS was statistically significant (p=0.02, log-rank test). On univariable Cox regression the hazard ratio for patients with a mutation in the resistance panel was 2.8 (95% CI: 1.1-7.1, p=0.03). In vitro, two out of three patient-derived cell lines with ESR1-MUT remained sensitive to abemaciclib, while those with mutation in RB1 or KRAS were less sensitive to abemaciclib. Conclusions: In our study, absence of co-existing genomic alterations in a curated panel was associated with greater clinical benefit with subsequent abemaciclib among patients with ESR1-MUT MBC with prior disease progression on endocrine therapy plus palbociclib/ribociclib. While a small dataset, this is the first demonstration of a genomic panel associated with continued CDK4/6 inhibitor sensitivity. Future directions include testing this panel outside of ESR1-MUT MBC and refining the panel in additional datasets with increased sample size, to guide therapy selection for patients with HR+ MBC. Citation Format: Jamie O Brett, Taronish D Dubash, Andrzej Niemierko, Veronica Mariotti, Leslie SL Kim, Jing Xi, Apurva Pandey, Siobhan Dunne, Azadeh Nasrazadani, Maxwell R Lloyd, Laura M Spring, Douglas Micalizzi, Maristela Onozato, Dante Che, Adam Brufsky, Kevin M Kalinsky, Cynthia X Ma, Joyce O’Shaughnessy, Hyo S Han, A. John Iafrate, Shyamala Maheswaran, Daniel A Haber, Aditya Bardia, Seth A Wander. Association between co-existing genomic alterations and abemaciclib benefit in patients with metastatic hormone receptor-positive breast cancer with ESR1 mutations following disease progression on prior endocrine therapy plus palbociclib or ribociclib [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD2-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-PD2-03
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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    detail.hit.zdb_id: 410466-3
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  • 9
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    Tumor Immune Microenvironment and Response to Neoadjuvant Chemotherapy in Hormone Receptor/HER2+ Early Stage Breast Cancer
    Elsevier BV ; 2022
    In:  Clinical Breast Cancer Vol. 22, No. 6 ( 2022-08), p. 538-546
    Details
    In: Clinical Breast Cancer, Elsevier BV, Vol. 22, No. 6 ( 2022-08), p. 538-546
    Type of Medium: Online Resource
    ISSN: 1526-8209
    URL: Article
    DOI: 10.1016/j.clbc.2022.04.002
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2175989-3
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  • 10
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    Abstract OT1-10-02: I-SPY2 endocrine optimization protocol (EOP): A pilot neoadjuvant endocrine therapy study with amcenestrant as monotherapy or in combination with abemacicilib or letrozole in molecularly selected HR+/HER2- clinical stage 2/3 breast cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. OT1-10-02-OT1-10-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. OT1-10-02-OT1-10-02
    Abstract: Background: There is no clinical equipoise on the best upfront management of patients with early-stage hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer (BC) that is high-risk by clinicopathologic criteria, and low-risk based on molecular profiling. These patients are unlikely to respond to chemotherapy. However, these patients still have risk, often risk of late recurrence, despite standard adjuvant endocrine therapy. Novel endocrine-based strategies that are more effective and tolerable than current standard therapies are needed for this population. Next-generation orally-bioavailable selective estrogen receptor degraders (oSERDs) with improved pharmacokinetic (PK) properties are promising potential therapies for HR+ BC. The oSERD amcenestrant has demonstrated a favorable safety profile and encouraging efficacy in a phase I/II dose escalation and expansion trial for heavily pre-treated patients with HR+ metastatic BC and is an attractive agent for assessment in the neoadjuvant BC setting. The neoadjuvant setting offers a unique opportunity to study novel agents and to assess early biological endpoints. However, one of the challenges in studying endocrine-based strategies in the neoadjuvant setting is the lack of a robust surrogate endpoint to reliably predict response and benefit. The I-SPY2 Endocrine Optimization Protocol (EOP) is a pilot sub-study within the main I-SPY2 TRIAL that will test amcenestrant alone or in combination with abemaciclib or letrozole. EOP will test the feasibility of using the I-SPY2 platform to test novel endocrine-based strategies in the neoadjuvant setting in patients with clinical high-risk, molecular low-risk, HR+/HER2- tumors, and will generate a rich database of imaging, molecular, and pathologic correlative endpoints that may potentially inform the improved assessment of response to neoadjuvant endocrine therapy. Trial Design/Eligibility/Accrual: The I-SPY2 EOP is a prospective, randomized, open-label trial specifically for patients with HR+/HER2-negative MammaPrint (MP) low-risk tumors that are at least 2.5 cm in size. Eligible patients are identified during the screening process for the parent I-SPY2 trial. The planned total accrual for the EOP is 120 patients. Patients are randomized 1:1:1 to one of 3 oral treatment arms: 1) amcenestrant 200 mg daily; 2) amcenestrant 200 mg daily + abemaciclib 150 mg bid; 3) amcenestrant 200 mg daily + letrozole 2.5 mg daily. Patients are treated for 6 months prior to surgery. Premenopausal women must receive concomitant monthly ovarian suppression. Serial breast MRIs, breast biopsies, blood, and patient reported outcomes (PROs) are being collected, and patients will be followed for 10 years for recurrence and survival. Serial dedicated breast PET (dbPET) scans and PKs will be assessed in a subset of patients. Objectives/Statistics: The primary objective of the EOP is to investigate the feasibility of enrolling and treating molecularly-selected patients with early stage HR+/HER2- MP low-risk BC in a randomized neoadjuvant trial using an oral-SERD backbone. Treatment will be determined to be feasible if ≥75% of enrolled patients complete ≥75% of assigned study therapy. Secondary objectives include the safety, tolerability, PROs, and PKs related to amcenestrant +/- abemacilcib and letrozole, as well as the assessment of imaging, pathologic, and molecular correlative endpoints as potential biomarkers of response to neoadjuvant endocrine therapy. Status: This study opened in May 2021. Accrual is ongoing. Citation Format: A. Jo Chien, Kevin M Kalinsky, Julissa Molina-Vega, Rita Mukhtar, Karthik Giridhar, Olufunmilayo I Olopade, Amrita Basu, Smita M Asare, Paul Henderson, Gillian Hirst, Ruixiao Lu, Ella Jones, Nola Hylton, Lamorna Brown-Swigart, Laura J van 't Veer, Douglas Yee, Ingrid Mayer, Laura J Esserman. I-SPY2 endocrine optimization protocol (EOP): A pilot neoadjuvant endocrine therapy study with amcenestrant as monotherapy or in combination with abemacicilib or letrozole in molecularly selected HR+/HER2- clinical stage 2/3 breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-10-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-OT1-10-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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