tbuckley/cabot-search huggingface dataset:
Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.
Authors: Nicole Odzer, Lajos Pusztai, Mariya Rozenblit
Journal: Journal of Clinical Oncology (2024)

1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as &lt; 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]
Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study.
Authors: Manali A. Bhave, Komal L. Jhaveri, Peter A. Kaufman, Philippe Georges Aftimos, Janine Margaret Lombard, Kostandinos Sideras, Seock-Ah Im, Cynthia X. Ma, Kuo-Ting Lee, Sung-Bae Kim, Yujia Li, Eunice Yuen, Shawn T. Estrem, Bastien Nguyen, Francesca Bacchion, Roohi Ismail-Khan, Muralidhar Beeram, Joohyuk Sohn
Journal: Journal of Clinical Oncology (2024)

1027 Background: Imlunestrant is a next-generation, oral SERD designed to deliver continuous ER-target inhibition. In the first-in-human Phase 1a/b EMBER study (NCT04188548), imlunestrant demonstrated favourable safety, PK, and clinical benefit when administered as monotherapy or with targeted therapy in ER+, HER2 - aBC. Here we present clinical data of imlunestrant with HER2 targeted therapy, in patients (pts) with ER+, HER2+ aBC enrolled in EMBER. Methods: Pts were randomized to imlunestrant (400mg po daily) + trastuzumab (H), with or without (±) abemaciclib (Part C) or received maintenance treatment with imlunestrant + H + pertuzumab (P) (Part E), at standard doses in 21-day cycles. Key eligibility (Part C): ≥ 2 prior HER2 directed regimens, no prior CDK4/6i or fulvestrant; (Part E): received 1 st line induction taxane chemotherapy (any duration) + H + P, without disease progression and ≤1 prior therapy for aBC. Key endpoints included safety, PK, ORR, CBR and PFS. Results: Overall, 45 pts with ER+/HER2+ aBC received the following combinations: imlunestrant + H (n=18), imlunestrant + H + abemaciclib (n=21; 1 pt received 800 mg imlunestrant), and imlunestrant + H + P (n=6). Baseline characteristics, safety, and preliminary efficacy are presented below (Table). Most TEAEs were grade 1-2. Common TEAEs with imlunestrant + H were fatigue (33%) and nausea (28%); with imlunestrant + H + abemaciclib were diarrhea (100%), neutropenia (57%), fatigue (52%) and nausea (48%); and with imlunestrant + H + P were diarrhea (50%) and arthralgia (50%). Imlunestrant PK was consistent with those previously reported with no drug-drug interactions observed with the combinations. From Part C, sequencing of baseline plasma ctDNA samples (n=37) identified prevalent mutations in TP53 (49%), PIK3CA (30%), ESR1 (24%), and GATA3 (14%). Clinical activity of imlunestrant in this ER+/HER2+ population, while based on small numbers, is promising. Conclusions: Imlunestrant in combination with trastuzumab ± abemaciclib or pertuzumab was well tolerated, showed no drug-drug interactions, and demonstrated preliminary antitumor activity in pts with ER+/HER2+ aBC. Clinical trial information: NCT04188548 . [Table: see text]
Clinical utility of an ultra-sensitive ctDNA NGS assay for the detection and monitoring in HR-positive, HER2-negative breast cancer.
Authors: Hao Liao, Jianxin Zhong, Xiao-ran Liu, Shao Bin, Haoran Tang, Cancan Jia, Feng Xie, Yue Zhang, Shidong Jia, Huiping Li
Journal: Journal of Clinical Oncology (2024)

e13076 Background: Breast cancer is the most diagnosed cancer in women globally, mainly as hormone receptor HR-positive, HER2-negative. While endocrine therapies have markedly improved clinical outcomes, the threat of disease progression persists. This study introduces an ultra-sensitive circulating tumor DNA (ctDNA) Next-Generation Sequencing (NGS) assay that was designed for in-depth genomic profiling of breast cancer patients undergoing endocrine therapy, aimed at detecting treatment resistance and monitoring disease progression. Methods: In this ongoing investigation, 46 patients with advanced HR-positive, HER2-negative breast cancer were enrolled, and plasma samples were collected subsequent to first-line aromatase inhibitor (AI) treatment and before the initiation of second-line treatment with fulvestrant. The study employed the PredicineCARE ULTRA, an ultra-sensitive liquid biopsy assay with a proprietary NGS panel and exceeds 100,000x coverage, allowing for the ultra-sensitive identification of genomic alterations, surpassing the detection capabilities of standard ctDNA NGS assays with approximately 20,000x coverage. Results: Within the cohort of 46 patients, the ultra-sensitive assay detected 193 somatic mutations, 95 gene copy number variants (CNVs), and a gene fusion involving FGFR3. The most commonly mutated genes, with a prevalence of 20% or more, were TP53 (33%), PIK3CA (26%), ATM (24%), ESR1 (22%), and BRCA2 (20%). These findings were benchmarked against results from a down-sampling algorithm designed to emulate ctDNA assays with 20,000x coverage. The ultra-sensitive assay revealed 31.3% more mutations (193 vs. 147) and 30.1% more CNVs. It was especially proficient in detecting mutations with allele frequencies (MAF) below 0.1%, identifying 10 additional mutations not observed at the standard ctDNA assay sensitivity, with the lowest MAF detected being 0.03% compared to the 0.1% threshold of the standard assay. This heightened sensitivity was evident in genes associated with targeted therapies and drug resistance, identifying 30.7% more variations in PIK3CA and 11.1% more in ESR1, with the lowest MAFs of 0.08% and 0.06%, respectively. The FGFR3-BAIAP2L1 gene fusion was also uniquely detected by the ultra-sensitive assay, with a MAF of 0.09%. Conclusions: The ultra-sensitive ctDNA NGS assay demonstrated superior detection of low-frequency mutations in HR-positive, HER2-negative breast cancer, significantly outperforming standard liquid biopsy assays. This enhanced sensitivity may offer profound implications for identifying more diagnostically positive patients who may benefit from targeted therapy such as PIK3CA and ESR1 inhibitors. This ultra-sensitive ctDNA assay will also enable early detection of treatment resistance and refined disease monitoring, potentially guiding more effective personalized therapies.
Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03.
Authors: Erika P. Hamilton, Sara A. Hurvitz, Seock-Ah Im, Hiroji Iwata, Giuseppe Curigliano, Sung-Bae Kim, Joanne Wing-Yan Chiu, Jose Luiz Pedrini, Wei Li, Kan Yonemori, Giampaolo Bianchini, Sherene Loi, Giuliano Santos Borges, Xian Wang, Thomas Bachelot, Shunsuke Nakatani, Shahid Ashfaque, Zhengkang Liang, Anton Egorov, Javier Cortes
Journal: Journal of Clinical Oncology (2024)

1025 Background: DESTINY-Breast03 (NCT03529110), a randomized, multicenter, open-label, phase 3 study, assessed the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC treated with ≥1 prior anti-HER2 regimen. Median (m) overall survival (OS) was not reached in either arm at the prior data cutoff (DCO; Jul 25, 2022). We report updated survival results, including efficacy and safety, after median duration of follow-up of 41 mo. Methods: Pts were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks. Primary endpoint was progression-free survival (PFS) by blinded independent central review (assessed at prior DCO); key secondary endpoint was OS. Other secondary endpoints included objective response rate (ORR), PFS, duration of response (DoR), PFS from time of randomization to progression on next line of therapy or death (PFS2), and safety. All secondary endpoints were based on investigator assessment. Results: 524 pts were randomized (T-DXd, n = 261; T-DM1, n = 263). As of Nov 20, 2023, median duration of follow-up was 43.0 mo (range, 0.0-62.9) for T-DXd and 35.4 mo (range, 0.0-60.9) for T-DM1. mOS (95% CI) was 52.6 mo (48.7-not evaluable [NE]) for T-DXd and 42.7 mo (35.4-NE) for T-DM1 (hazard ratio [HR], 0.73), with 110 (42.1%) and 126 (47.9%) OS events, respectively. OS rate (95% CI) at 36 mo was 67.6% (61.3-73.0%; T-DXd) vs 55.7% (49.2-61.7%; T-DM1). mPFS was 29.0 mo for T-DXd and 7.2 mo for T-DM1; PFS rate (95% CI) at 24 mo was 55.8% (49.1-62.0%; T-DXd) vs 20.6% (15.4-26.4%; T-DM1). mPFS2 was 45.2 mo (T-DXd) vs 23.1 mo (T-DM1). Median treatment duration was 18.2 mo (range, 0.7-56.6) with T-DXd vs 6.9 mo (range, 0.7-55.2) with T-DM1; rates of treatment-emergent adverse events (TEAEs) were consistent with prior DCO. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 16.7% of pts with T-DXd (4 new events [all grade 2] since prior DCO) vs 3.4% with T-DM1 (1 new event [grade 1]); neither arm had grade 4 or 5 events. Key efficacy and safety results are shown in the table. Conclusions: The superiority of T-DXd over T-DM1 was reinforced in this long-term analysis, as observed by clinically meaningful improvement in OS, PFS, and PFS2, consistent with prior DCO. The safety profile of T-DXd continues to be manageable with no cumulative toxicities observed with longer follow-up. Clinical trial information: NCT03529110 . [Table: see text]
Use of Oncotype vs. Breast Cancer Index (BCI) for extended endocrine therapy decisions: A single center analysis in stage IA hormone receptor positive breast cancer.
Authors: Iuliia Kovalenko, Faith Seltun, Alice He, Chandi Garg, Maha Azhar, Ekaterina Proskuriakova, Yijin Wert, Kit Yu Lu
Journal: Journal of Clinical Oncology (2024)

e13083 Background: Extended Endocrine Therapy (EET) for hormone receptor positive HER-2 negative early-stage breast cancer reduces late recurrence risks but raises concerns about toxicity. Biomarker tests like the Breast Cancer Index (BCI) are vital for identifying patients who could benefit from continued ET, reassuring others against unnecessary extension. This study evaluates prognostic implications for both Oncotype Dx (Recurrence score, RS) and BCI amidst concerns about added testing costs in patients with early stage, estrogen receptor (ER) positive breast cancer. Methods: This is a single institution retrospective review of Stage IA ER positive HER-2 negative breast cancer patients who underwent both Oncotype Dx and BCI testing from January 2021 to December 2023. Pearson's correlation coefficient (r) was used to assess the linear relationship between the assays (p&lt;0.05 for significance), analysis was performed with SAS software, version 9.4. Results: Fifty-eight patients with Stage IA ER positive HER-2 negative breast cancer who had both Oncotype and BCI results were identified (100% female; mean age 72.2 years [54-87]). After a median followed up of 72 months (63-75), no systemic or locoregional recurrences were reported. A low positive correlation between Oncotype and BCI was observed across the entire cohort (r=0.4058; p=0.0016). However, subgroup analysis showed no significant correlations: Oncotype &lt;11 (n=17; r=0.2415; p=0.3504), Oncotype ≤18 (n=43; r=0.0914; p=0.5600), Oncotype &lt;26 (n=51; r=0.2530; p=0.0733); Oncotype ≥26 (n=7; r=-0.5634; p=0.1878). Correlation was also not found in patients with Grade 1 tumor (n=16; r=0.3138; p=0.2365). Thirty-nine patients (67.24%) had their treatment recommendation changed based on BCI results. Side effects from ET affected 15 patients (25.86%) and included arthralgias (60%, n=9), hot flashes (26.67%, n=4), depression (13.33%, n=2), insomnia (6.67%, n=1), and others (53.3%, n=8). Twenty-two patients (37.93%) developed new osteopenia, and 6 (10.34%) new osteoporosis while on EET. Eight patients (13.79%) had ET interruption during their treatment course. Conclusions: Despite inclination towards cost-saving measures, Oncotype DX may be more useful to give prognosis in the early adjuvant period whereas BCI is more useful to evaluate late recurrence risk. Low or high Oncotype scores and tumor grade may not align with BCI findings. Considering the importance of managing toxicity against the risk of late recurrence, incorporating BCI testing can enhance EET recommendations, even for Stage I, node-negative, ER positive patients.
H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive (ER+), HER2 negative (–) breast cancer (BC).
Authors: Erika P. Hamilton, Timothy J. Pluard, Judy S. Wang, Aki Morikawa, Stephen R. D. Johnston, Elizabeth Claire Dees, Christos Vaklavas, Anne C. Armstrong, Pamela N. Munster, Nisha Unni, Gail Lynn Shaw Wright, Fadi Kayali, Tingting Song, Yuanxin Rong, Kohei Yamaguchi, Dejan Juric
Journal: Journal of Clinical Oncology (2024)

1015 Background: H3B-6545 is a novel selective ER covalent antagonist (SERCA) that inactivates wild-type and mutant ERα. This phase 1/2 study aimed to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), and characterize safety and efficacy of H3B-6545 in women with advanced/metastatic ER+, HER2– BC. Methods: This multicenter, open-label study included dose-escalation [ph1] and -expansion [ph2] phases. Females (postmenopausal or concurrently receiving a luteinizing hormone-releasing hormone agonist) with ER+, HER2–BC who had disease progression on standard therapy were eligible. Prior therapy must have included a minimum of 2 hormonal therapies (HTs), or 1 HT + 1 chemotherapy, or 1 HT + a CDK4/6 inhibitor. H3B-6545 was administered orally QD at doses of 100-600 mg. The MTD was the highest dose at which ≤1 of 6 patients (pts) had a dose-limiting toxicity (DLT). In ph2, efficacy of the RP2D was examined. The primary endpoints were determination of RP2D (ph1) and efficacy (ph2; including objective response rate [ORR], duration of response [DOR], and progression-free survival [PFS] per RECIST v1.1 by investigator, and overall survival [OS]). Safety and PK were secondary endpoints. Results: At data cutoff (30 Nov 22), 151 pts received ≥1 dose of H3B-6545 during ph1 or ph2. Pts had a median (m [range]) of 2 (1-7) prior endocrine- and 1 (1-6) non-endocrine–containing therapies; 90.1% of pts received prior CDK4/6 inhibitors. During ph1, DLTs of grade (G) 3 rash (n=1) and G 3 fatigue (n=1) were observed at 600 mg; thus, 450 mg was determined to be the MTD/RP2D. In the full analysis set (N=151), 100% and 50.3% of pts had any grade and G ≥3 treatment-emergent adverse events (TEAEs), respectively. TEAEs leading to drug interruption, dose reduction, and withdrawal occurred in 38.4%, 20.5%, and 8.6% of pts, respectively. Nausea (45.7% [2.0% G ≥3]), sinus bradycardia (44.4% [0% G ≥3]), and diarrhea (41.1% [1.3% G ≥3]) were the most common TEAEs. QT prolongation occurred in 9.9% [3.3% G ≥3] of pts. Among 94 response-evaluable pts treated at 450 mg, ORR was 20.2% (95% CI 12.6–29.8) and clinical benefit rate (CBR) was 41.5% (95% CI 31.4–52.1); mPFS (95% CI) was 5.06 (3.15–7.26) months. Among all pts treated at 450 mg (n=115), mOS (95% CI) was 21.52 (16.56–25.46) months. Plasma concentration of H3B-6545 increased as dose increased. Additional results are shown (Table). Conclusions: H3B-6545 had a low rate of G ≥3 TEAEs and showed clinically meaningful antitumor activity in heavily pretreated female patients with ER+, HER2– BC. Clinical trial information: NCT03250676 . [Table: see text]
Evaluating the impact of GLP-1 receptor agonists on weight management in patients with breast cancer undergoing endocrine therapy: A comparative analysis.
Authors: Daniela Urueta Portillo, Marcela Mazo- Canola, Sara Alhaj
Journal: Journal of Clinical Oncology (2024)

e13063 Background: Obesity has been linked to increased risk of recurrence in postmenopausal patients with history of Hormone Receptor positive + (HR) breast cancer. making weight management very important in this patient population. The use of endocrine therapy with aromatase inhibitor (AI) or selective estrogen modulators (SERM) in this population has been linked to weight gain (PMID: 37831449). This study evaluates the effectiveness of GLP-1 medications (Semaglutide, Liraglutide, Dulaglutide, Tirzepatide) in these patients, comparing weight loss outcomes to those in non-cancer populations. Methods: A retrospective analysis was conducted on breast cancer patients who were receiving endocrine therapy (AI or SERM) in combination with GLP-1 medications. The study primarily focused on evaluating mean baseline Body Mass Index (BMI), the proportion of patients with a BMI ≥30, and the mean percentage change in BMI at the 12-month mark, including 95% confidence intervals (CIs) for these changes. Results: The study found that the mean percentage changes in BMI at 12 months for the GLP-1 medications were as follows: Semaglutide resulted in a -4.34% change (95% CI [-7.66%, -1.02%]), in stark contrast to a -14% change reported in the general population (PMID: 33567185); Liraglutide showed a -3.51% change (95% CI [-8.48%, 1.45%]), compared to -8.4% (PMID: 26132939); Dulaglutide led to a -2.33% change (95% CI [-6.80%, 2.13%]), against -10.0% (PMID: 34189841); and Tirzepatide recorded a 2.31% change (CI [-11.47; 20.54]) relative to -15.0% (PMID: 35658024). These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population. Conclusions: The study concludes that breast cancer patients on endocrine therapy exhibit less significant weight loss with GLP-1 medication treatment than what has been observed in the general population. This suggests that endocrine therapy may reduce the weight-loss efficacy of GLP-1 medications in this particular patient group. Further prospective research is essential to elucidate the mechanisms behind this attenuated response and to develop effective weight management strategies tailored for breast cancer patients undergoing endocrine therapy.
Effect and acceptability of jasmine compound essential oil for premenopausal breast cancer survivors suffering from genitourinary syndrome of menopause: A prospective interventional study.
Authors: Mo Zou, Xiaorui Li, Tao Sun
Journal: Journal of Clinical Oncology (2024)

1063 Background: Genitourinary syndrome of menopause (GSM) includes dyspareunia, vaginal dryness, vaginal burning, urinary urgency, and recurrent urinary tract infections. Breast cancer survivors (BCSs) exhibit more severe symptoms of GSM than healthy aging women, especially premenopausal BCSs in sexually active lifetime. GSM detrimentally impacts their quality of life and contributes to the premature cessation of endocrine therapy for breast disease. This study aims to explore the efficacy and safety of Jasmine compound essential oil in the treatment of GSM in premenopausal breast cancer women. Methods: Premenopausal sextually-active women with hormone receptor (HR) positive stage I to III BC taking ovarian function suppression (OFS) treatment and endocrine therapy with self-reported vaginal dryness, dyspareunia, or decreased libido were enrolled to the 12 weeks topically applied Jasmine compound essential oil trial. E2 and FSH was measured at baseline and weeks 12. A series of validated sexual quality-of-life questionnaires were completed at baseline, and subsequently at weeks 4, 8, and 12. The primary endpoint is the improvement in sexual pain evaluated based on the Female Sexual Function Index scale (FSFI). Acceptability was measured by patient preference and reported intention to continue using the products. Gynecologic examinations and metagenomic profiling of the vaginal microbiota were conducted at baseline and post-treatment for patients in an exploratory cohort. Results: Overall, 96 BCSs signed consent (mean [range] age, 45 [32-55] years) and 89 completed 12 weeks of treatment. E2 and FSH were maintained within the postmenopausal range without significant fluctuations during the treatment. Topically applied Jasmine compound essential oil resulted in significant improvements in dyspareunia, vaginal dryness, irritation and quality of life over time (all P&lt; 0.001). Both BCSs and their sexual partners reported being satisfied with the essential oil treatment and the adherence rate reached 95% (SD 10). In the 20-patient exploratory cohort, there were improvements in vaginal pH (baseline mean 6.07 compared with 12-week mean 4.68[ P&lt;.001]), and vaginal maturation index (45.3 compared with 52.1[ P&lt;.001]). We also observed a positive influence on the vaginal microbiota after intervention. In patients with elevated baseline abundance of Lactobacillus in the vaginal microbiome, there was a more pronounced improvement in scale scores following essential oil access. Conversely, a high baseline abundance of Escherichia coli may be considered a detrimental factor associated with less benefit from essential oil. Conclusions: Jasmine compound essential oil could relieve vaginal symptoms and improve vaginal health in breast cancer survivors who have experienced menopause after cancer treatment.