Kooperativer Bibliotheksverbund

In: Cancers, MDPI AG, Vol. 14, No. 10 ( 2022-05-17), p. 2468-

Abstract: Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnosis to T-DM1 initiation increased from 10 to 14 months (2013–2019), and median TTNT increased from 4.4 to 10.2 months (2013–2018). Over time, prior H + P prevalence significantly increased with no observable impact on T-DM1 effectiveness. Drug approval timing should be considered when assessing treatment effectiveness within a sequence.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers14102468

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2527080-1

In: The Breast, Elsevier BV, Vol. 66 ( 2022-12), p. 262-271

Type of Medium: Online Resource

ISSN: 0960-9776

URL: Article

DOI: 10.1016/j.breast.2022.10.008

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2009043-2

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 6520-6520

Abstract: 6520 Background: Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. Methods: We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 to Feb 30, 2021. rwPFS was defined as the time from start of first-line systemic therapy for MBC to disease progression or death. TTNT was defined as the time from start of first-line systemic therapy until start of next line of therapy. The nonparametric Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model in the Weibull margin distribution. Kendall’s tau (τ) with its 95%CI was calculated across the entire dataset, and within each disease subgroup defined by receptor (ER and/or PR status defined as hormone receptor [HR], and HER2) status. This work was conducted on behalf of the imCORE network and the Dana-Farber Cancer Institute. Results: Overall, 9,770 patients with MBC were included. Median age was 63 years (IQR: 54-72 years). HR+/HER2- disease represented the most frequent MBC subtype (n=6,287; 64.4%), followed by HER2+ (n=2,096; 21.5%) and triple negative (n=1,387; 14.2%) disease. Median f/u was 41.5 months (95%CI: 40.4 to 42.8). Median OS in the overall population was 32.4 months (95%CI: 31.2 to 33.3). Median rwPFS was 11.5 months (95%CI: 11.1 to 11.9), and median TTNT was 11.1 months (95%CI: 10.7 to 11.5). Across the entire population, the correlation of rwPFS with OS was 0.54 (95%CI: 0.53-0.56), while the correlation of TTNT with OS was 0.47 (95%CI: 0.46-0.48) (Table). Conclusions: rwPFS and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within the different disease subgroups. [Table: see text]

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2022.40.16_suppl.6520

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2022

detail.hit.zdb_id: 2005181-5

In: Reproductive BioMedicine Online, Elsevier BV, Vol. 28, No. 4 ( 2014-04), p. 522-529

Type of Medium: Online Resource

ISSN: 1472-6483

URL: Article

DOI: 10.1016/j.rbmo.2013.12.007

Language: English

Publisher: Elsevier BV

Publication Date: 2014

detail.hit.zdb_id: 2057455-1

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e13028-e13028

Abstract: e13028 Background: Dual HER2 blockade with pertuzumab (P) + trastuzumab (H), combined with taxane induction therapy, is the standard of care for the first-line treatment of patients with HER2-positive MBC. In clinical practice, after achieving clinical benefit with approximately 4–6 cycles of PH + taxane induction, maintenance therapy is continued with PH only until disease progression or unmanageable toxicity. Approximately 50–60% of patients with HER2-positive MBC also have concurrent HR expression and may receive ET in combination with PH. This study investigated the clinical characteristics and outcomes of patients initiating ET combined with PH as maintenance therapy after completion of PH + taxane induction. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Patients with HER2-positive and HR-positive MBC who initiated an ET between Jan 1, 2012 and Feb 28, 2021 with concomitant PH after receiving at least four cycles of first-line PH + taxane induction were included. The index date was the date of ET initiation. Progression data were abstracted from the medical charts. Mortality data were abstracted and combined with patient-level structured data (obituaries and Social Security Death Index). rwPFS was defined as the time from index date until first progression event 〉 14 days after the index date, or date of death; otherwise, patients were censored on the date of last clinical note abstraction. Baseline characteristics were described using summary statistics, and rwPFS in the maintenance setting was described using a Kaplan–Meier estimator from the index date. Results: Of 24,690 patients diagnosed with MBC in the database, 252 (1%) met the eligibility criteria. All patients were female. The median age was 56.6 years; 149 patients (59%) were diagnosed with de novo MBC; 248 (98%), with estrogen receptor-positive disease; and 182 (72%), with progesterone receptor-positive disease. One hundred ninety-three patients (77%) received an aromatase inhibitor as ET. The median number of taxane cycles received prior to the index date was six. Median maintenance rwPFS was 21.4 months (95% confidence interval = 16.1, 25.3). Conclusions: Given the therapeutic opportunity presented by HER2/HR co-expression and the favorable maintenance rwPFS shown here with PH + ET following taxane induction, the investigation of more potent ETs combined with PH is justified in order to further improve outcomes in first-line HER2-positive/HR-positive MBC.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2022.40.16_suppl.e13028

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2022

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 1037-1037

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2018.36.15_suppl.1037

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2018

detail.hit.zdb_id: 2005181-5

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 7 ( 2011-07), p. 1703-1709

Abstract: The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). Methods and Results— We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤70% or antigen ≤592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123] , respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤57%) were significantly associated with early-onset preeclampsia (OR=2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin ( 〉 57 ng/mL) (OR=3.4 [1.2 to 9.7]). Conclusion— Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.

Type of Medium: Online Resource

ISSN: 1079-5642 , 1524-4636

URL: Article

DOI: 10.1161/ATVBAHA.111.223610

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2011

detail.hit.zdb_id: 1494427-3

In: The Breast, Elsevier BV, Vol. 69 ( 2023-06), p. 441-450

Type of Medium: Online Resource

ISSN: 0960-9776

URL: Article

DOI: 10.1016/j.breast.2023.01.007

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2009043-2

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS10-20-PS10-20

Abstract: OBJECTIVES Over the last decade, new treatment options have transformed the standard of care for patients (pts) with HER2-positive EBC and the treatment landscape continues to evolve. The primary objectives of our study were (1) to describe and compare the demographic and clinical characteristics of pts with HER2-positive EBC who received neoadj or adj treatment, (2) to describe the common neoadj and adj regimens according to hormone receptor (HR) status, and (3) to describe trends in neoadj treatment use from 2011 to 2019 in a US real-world setting. METHODS Unstructured and structured electronic health record-derived data were analyzed from the US Flatiron Health de-identified database (2011-2020), a longitudinal database of & gt;2.4 million pts with cancer in & gt;280 clinics, largely from community-based practices. Eligible pts had HER2-positive EBC (diagnosis: Jan 1, 2011-Jul 31, 2019; follow-up: until Feb 29, 2020). Systemic or oral anti-neoplastic treatments with initiation either prior to (neoadj) or within 6 months (adj) of the first primary surgery date were included. Adj treatment also required at least 6 months of follow-up and was captured for up to 1 year after initiation of adj therapy. RESULTS Pts with HER2-positive EBC treated in the neoadj setting, versus those in the adj setting alone, were more likely to be younger, pre-menopausal, have HR-negative disease, clinical stage II or III stage disease (refer to footnote in Table 1), have received treatment at an academic center, and were ~2 times as likely to have bilateral mastectomies (Table 1). Conversely, race/ethnicity as well as tumor grade, histology and laterality did not differ by neoadj versus adj treatment. The most common therapies are presented in Table 1. There was an upward trend in the annual percentage of pts diagnosed with HER2-positive EBC who initiated neoadj treatment starting in 2011 ( & lt;20% of pts) and peaking in 2017 (~50% of pts). Most pts (78%) who received neoadj therapy were treated with a taxane-based chemotherapy regimen and a dual blockade of HER2 with trastuzumab plus pertuzumab (HP). A minority of neoadj pts (11%) received an anthracycline-based regimen plus HER2-targeted therapy. As expected, most pts received HER2-targeted therapy alone with HP post-surgery. The most common chemotherapy for adj-only pts included a taxane-based regimen combined with H (+/- P). Hormonal therapy was mostly administered post-surgery (adj-continuation: 61%; adj-only: 78%) with low use in the neoadj setting (9%). When evaluating pts by HR status, pts with HR-positive EBC more commonly received hormonal and ‘other’ therapy; adj-only pts with HR-negative disease more commonly received HER2-targeted therapies with taxanes (83% v 54%), irrespective of the additional use of platinum-based chemotherapy (64% v 38%) or anthracyclines (15% v 8%). CONCLUSIONS Neoadj therapy use has increased, which is in line with changes in the standard anti-HER2 therapies that have occurred since 2013. Despite considerable variation, neoadj pts are mostly treated with dual HER2 blockade and chemotherapy, with a preference for taxane-based regimens. Table 1. Summary of key demographics and clinical characteristicsCharacteristic*Neoadj (n = 394)Adj (n = 696)Age at diagnosis, mean (IQR)55 (46, 64)61 (51, 69)Race / ethnicity- Non-Hispanic white237 (60)433 (62)- Other134 (34)218 (31)- Unknown23 (6)45 (7)Menopausal status- Postmenopausal219 (56)495 (71)ECOG PS- 0203 (52)277 (40)- 152 (13)86 (12)- 2+7 (2)13 (2)- Unknown132 (34)320 (46)Combined clinical stage†- Clinical stage I30 (8)364 (52)- Clinical stage II167 (42)216 (31)- Clinical stage III104 (26)57 (8)- Unknown93 (24)59 (9)Type of surgery- Lumpectomy155 (41)435 (63)- Mastectomy225 (59)261 (37)- Unknown14 (4)0Year of Diagnosis- 2011-1245 (11)180 (26)- 2013-14109 (28)209 (30)- 2015-1698 (25)170 (24)- 2017-19142 (36)137 (20)Practice type (EHR format)- Community348 (88)659 (95)- Academic46 (12)37 (5)ER-positive and/or PR-positive280 (71)557 (80)Most common treatment regimens, n (%)‡Pts with HER2-positive EBC, with available treatment dataNeoadjn = 280- TCH / TCHP43 (15) / 176 (63)- ACT + H/HP§14 (5) / 18 (6)- Any hormonal therapy25 (9)Adj continuationn = 266- H / HP only171 (64) / 38 (14)- Any hormonal therapy163 (61)- T (H / HP) + other¶35 (13)Adj-onlyn = 642- Any hormonal therapy500 (78)- TCH / TCHP223 (35) / 43 (7)- T (H / HP) + other¶106 (17)*P & lt;0.05 (t-test) when comparing pts in the neoadj and adj treatment groups for the clinical characteristics listed (with the exception of race / ethnicity where no major differences were noted). †Clinical stage prior to the start of systemic treatment, which is close to the time of diagnosis for neoadj pts and after the time of surgery for adj pts. ‡‘Other’ therapies accounted for 5% of regimens. §The majority of anthracycline use was a TCH / HP regimen. ¶‘Other’ treatments include CD20 monoclonal antibody, CDK 4/6 inhibitors, antimetabolites (e.g., gemcitabine) and clinical trial study drugs (not specifically listed/known). A, anthracycline; adj, adjuvant; C, a platinum-based compound; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EHR, electronic health record; ER, estrogen receptor; H, trastuzumab; IQR, interquartile range; neoadj, neoadjuvant; P, pertuzumab; PR, progesterone receptor; pts, patients, T, taxane. Citation Format: Preet K. Dhillon, Carlos Flores, Thibaut Sanglier, Vincent Antao, David Tesarowski, Anita Fung, Devin Incerti, Eleonora Restuccia, Patricia Luhn. Neoadjuvant (neoadj) and adjuvant (adj) treatment patterns in HER2-positive early breast cancer (EBC): Analysis of US real-world oncology data [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 PS10-20.

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/1538-7445.SABCS20-PS10-20

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2021

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-13-22-P2-13-22

Abstract: Background: Continuing trastuzumab beyond disease progression was one of the most important paradigm changes in Oncology and is recommended by all guidelines. The reason behind it is that metastatic breast cancer (MBC) progresses much faster when the HER2 pathway is not blocked. However, the amount and robustness of data supporting this recommendation is limited, leading to lack of approval and/or access to this therapeutic strategy in many countries. The present study aims to provide additional data supporting that continuing trastuzumab (Tras) + chemotherapy (CT) may substantially improve outcomes of patients with MBC. Methods: We conducted a retrospective cohort study, using an U.S Electronic Health Record-derived de-identified database (Flatiron Health). Patients with MBC who were previously treated with anti-HER2 therapies and initiated as third line treatment CT combined with trastuzumab-based therapy (Tras+CT) or CT alone (index date) from 01/01/12-31/12/20 were included. An intention-to-treat approach was used to estimate the direct average treatment effects (ATEs) of initiating Tras+CT versus CT only on the Hazard Ratios for overall survival (OS) and real world progression free survival (rwPFS). Potential sources of confounding were identified using directed acyclic graphs and included clinical characteristics at index date as well as prior duration of similar treatments. Propensity score of received Tras+Ct vs CT was estimated using covariate balancing propensity score methodology. ATE was estimated using inverse probability of treatment weighting (IPTW) for Cox-proportional hazard models. Hazard ratios 95% confidence intervals were estimated using empirical bootstrap. Results: Three hundred and thirty seven patients initiated either treatment strategy (median age 60 years old), of these 288 patients initiated Tras+CT (49% trastuzumab based regimens, 43% T-DM1 based regimens and 8% including newer agents) and 49 received CT only. The median OS and median rwPFS were 23 months and 6 months for Tras+CT treated patients and 11 months and 5 months for CT treated patients. In the weighted population the median OS and median rwPFS were 19 months and 6 months for Tras+CT treated patients and 10 months and 5 months for CT treated patients resulting in hazard ratios of 0.29 [0.15-0.54] and 0.69 [0.45-1.06] for OS and rwPFS respectively. Conclusion: Including trastuzumab-based therapy in addition to CT in the third line treatment (Trast+CT) was associated with markedly improved survival outcomes compared with CT only. This study represents how HER2 blockade is maintained in third line in the U.S. over the period of time covered by the study. Limitations of the study could be unmeasured confounding factors, and the potential channeling of patients with lower socio-economic status towards CT treatment only. The latter could be similar to what is happening to patients treated in countries where continuing trastuzumab beyond progression is not accessible. This study provides further and strong support for this treatment strategy that should be accessible to all MBC patients across the world. As next steps, these results will be confirmed using other real-world datasets from different countries, including countries without current access to trastuzumab beyond progression. Citation Format: Thibaut Sanglier, Ryan Ross, Tianlai Shi, Joao Mouta, Fatima Cardoso. Comparative effectiveness of initiating chemotherapy with or without trastuzumab based regimens as third line treatment for metastatic 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 P2-13-22.

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/1538-7445.SABCS21-P2-13-22

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