BACKGROUND:Adjuvant endocrine therapy reduces breast cancer recurrence, but symptom burden contributes to nonadherence, particularly among Black women. We examined how patient sociodemographic factors and perceived discrimination are associated with symptoms and Black-White differences in symptoms during early treatment course of adjuvant endocrine therapy. METHODS:We conducted a post hoc analysis using survey data collected at study enrollment in the THRIVE trial from November 15, 2018, to June 11, 2021, among women with early-stage breast cancer. Symptom burden was assessed by the Functional Assessment of Cancer Therapy-Endocrine Subscale within 8 weeks of adjuvant endocrine therapy initiation. Covariates included sociodemographic and clinical information and perceived discrimination. Multivariable regressions and Kitagawa-Oaxaca-Blinder decomposition evaluated how these patient characteristics are associated with Black-White differences in symptoms. RESULTS:Among 272 participants, 35.7% self-identified as Black and 64.3% as White. Black women reported more symptoms (lower Functional Assessment of Cancer Therapy-Endocrine Subscale scores) than White women (60.7 vs 64.3, P = .004) and similar discrimination scores (5.44 vs 5.54, P = .17). Experiencing less discrimination (ie, each unit increase in discrimination score, 1.93, 95% confidence interval [CI] = 0.08 to 3.78), older age groups (65-83 vs 30-49 years: 4.84, 95% CI = 1.15 to 8.54), and higher income (≥400% vs <200% federal poverty level = 5.72, 95% CI = 2.12 to 9.33) was associated with lower symptom burden. Decomposition analyses attributed 84.6% of Black-White symptom differences to patient characteristics, with income explaining the largest proportion, while perceived discrimination did not explain symptom burden differences. CONCLUSIONS:Black women experienced higher early symptoms during adjuvant endocrine therapy. Although perceived discrimination was associated with greater symptom burden, it did not clinically or statistically significantly explain Black-White differences in symptoms. Income explained the largest portion of Black-White symptom differences. Addressing income inequality is essential for equitable symptom management.

Nausea and vomiting beyond 5 days after emetogenic chemotherapy or antibody–drug conjugate (ADC) therapy are common, yet the role of neurokinin-1 (NK1) receptor antagonists in this setting remains underrecognized. We used pharmacokinetic/pharmacodynamic (PK/PD) modeling to estimate the NK1 receptor occupancy (RO), a proxy for clinical efficacy, for up to 20 days after a single 300 mg dose of oral netupitant, 3-day oral aprepitant (125 mg on day 1; 80 mg on days 2–3), or a single 165 mg dose of oral aprepitant. Data from previous PK studies were analyzed by compartmental modeling. Positron emission tomography studies assessing striatal NK1 RO were used to develop maximum drug effect PD models, which were fitted to NK1 RO data as a function of plasma concentrations. Model predicted NK1 RO exceeded 90

Nausea and vomiting are common, distressing side effects associated with chemotherapeutic regimens, resulting in reduced quality of life and treatment adherence. Appropriate antiemetic prophylaxis strategies may reduce/prevent chemotherapy-induced nausea and vomiting (CINV). Historically, investigators assessed antiemetics up to 120 hours after chemotherapy. However, CINV can extend beyond this time. Thus, the effect of antiemetics during the long-delayed period (>120 hours) requires investigation. Emerging treatment options, including certain antibody-drug conjugates (ADCs), are associated with high rates of acute and late-onset nausea and vomiting that can last for extended duration. With the increasing number of ADCs approved and in development, there is urgency to control nausea and vomiting in patients receiving these new therapies. In this narrative review, we present the emetogenic potential of ADCs and CINV in the long-delayed period along with antiemetic prophylaxis strategies used to date. We also discuss the promising role of the fixed-combination antiemetic NEPA ([fos]netupitant plus palonosetron) in controlling long-delayed nausea and vomiting, addressing characteristics that may contribute to its longer efficacy duration compared to other antiemetics. Finally, we highlight encouraging results with NEPA in patients receiving the ADCs trastuzumab deruxtecan or sacituzumab govitecan, which suggest NEPA may be an effective antiemetic prophylaxis in these settings.

Supplementary Figure S1) To assess the robustness and reproducibility of the CRC prediction models, we evaluated their performance on samples processed under varying conditions. This figure shows the performance of the final CRC model, after retraining on the full training dataset, across the robustness and reproducibility studies. Specifically, we analyzed the precision of model scores using a set of precision study samples processed by two different operators, instruments, and, when available, reagent lots. Two separate precision studies were performed: One that started from separate plasma aliquots and tested variability derived from extraction. For this study, once RNA was extracted, it was included in the same batch for processing through the rest of the assay (left panel). Across the replicates, the scores remained consistent, with no instances where changes in scores were significant enough to cross the cutoff threshold into the opposite category. The second study used pools of RNA that were diluted 2-fold to generate more input material and then distributed in replicates across different batches starting from library preparation and through the rest of the assay (middle panel). These experiments ensured that normal laboratory variability did not significantly impact the model’s predictive outputs. Finally, we compared the scores of 40 samples where 2 separate plasma aliquots were processed at different times through the assay ( Right panel). The high correlation of model scores across these conditions demonstrates the model’s robustness to technical variability and underscores its reliability for real-world applications

BACKGROUND:Despite adjuvant endocrine therapy (ET), recurrence is still a concern for patients with HR+/HER2- early breast cancer (EBC). We assessed recurrence risk in real-world patients with stage II/III HR+/HER2- EBC treated with adjuvant ET. METHODS:A retrospective analysis was conducted using the ConcertAI Patient360 database (January 1995 to April 2021) of patients with stage II/III HR+/HER2- EBC ≥18 years who underwent surgery and received adjuvant ET. Risk of recurrence was assessed using invasive disease-free survival (iDFS) with adapted STEEP criteria. An ET subanalysis evaluated iDFS, distant disease-free survival, and overall survival in patients receiving adjuvant non-steroidal aromatase inhibitors (NSAI) vs tamoxifen. RESULTS:In the full analysis cohort (N = 3133), the risk of an iDFS event was 26.1 % at 5 years, rising to 45.0 % at 10 years. Among patients with stage II disease, the risk of an iDFS event at 5 and 10 years was 22.7 % and 40.5 %, respectively; stage III 5- and 10-year risk was 40.4 % and 62.9 %. Patients with node-negative disease had 5- and 10-year risks of 22.1 % and 36.9 %, respectively; node-positive 5- and 10-year risk was 28.9 % and 49.4 %. ET subanalysis showed improved iDFS with NSAI ± ovarian function suppression vs tamoxifen ± ovarian function suppression (HR, 0.83; 95 % CI, 0.69-0.98; p = 0.031); this trend was observed regardless of menopausal status. CONCLUSIONS:This real-world study highlights the considerable risk of recurrence with adjuvant ET in patients with stage II or III HR+/HER2- EBC (including node-negative disease) and confirms the need for improved treatment options.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Early detection offers the best opportunity for effective treatment. Although CRC screening methods exist, there remains a need for a high performing blood test to both improve adherence and detect early stage disease. We have previously identified and developed a novel category of cancer-associated, small orphan non-coding RNAs (oncRNAs), and combined them with generative AI modeling to develop a liquid biopsy platform. This platform has demonstrated high sensitivity and specificity for detection of early stage disease across several types of cancer. In this study, we developed an oncRNA- and AI-based assay and analyzed it in a separate, independent test set to evaluate its generalizability and its ability to detect CRC across different cancer stages. We utilized The Cancer Genome Atlas (TCGA) small RNA profiles to discover a library of pan-cancer oncRNAs that were significantly enriched among tumors compared to adjacent normal tissues spanning multiple tissue sites. The diagnostic performance of these oncRNAs was evaluated in plasma using a training and independent test cohort. Our training cohort included 613 samples (388 CRC and 225 asymptomatic controls) from six different sources (mean age: 63.7 years, 35.9% female). 37.6% of the cases were classified as stage I/II and 60.8% as stage III/IV. Further, we acquired 192 samples (113 CRC and 79 asymptomatic controls) from a separate cohort for testing (average age: 62.6 years ; 51.6% female). In the test set, 52.2% of cases were classified as stage I/II and 47.8% as stage III/IV. We processed 1 ml of plasma for each sample through our universal, automated cell-free RNA workflow and sequenced at an average depth of 58 million 100-bp single-end reads. A generative AI model was trained using 5-fold cross-validation (CV) to predict CRC, and then applied on the separate, independent test set. Our oncRNA-based generative AI model achieved an overall AUC of 0.93 (95% CI: 0.91-0.95) for prediction of CRC versus cancer-free controls in CV, and an overall AUC of 0.95 (0.93-0.98) in the independent test set. At 90% specificity, overall model sensitivity was 81.7% (77.5%-85.4%) by CV in the training data, and 88.5% (81.1%-93.7%) in the test set. For stage I CRC, the model has a sensitivity of 72.1% (59.9%-82.3%, N=68) by CV in the training data, and 80.0% (51.9%-95.7%, N=15) in the test set, both at 90% specificity. We demonstrate that blood-based cell- free RNA can be used for accurate and generalizable early stage detection of CRC. This approach, leveraging a distinct RNA biomarker, has the potential to overcome performance plateaus seen with conventional DNA-based methods in early-stage CRC detection. It offers a promising alternative for blood-based CRC screening in patients and could complement existing DNA- and methylation-based platforms. Amir Momen-Roknabadi, Mehran Karimzadeh, Nae-Chyun Chen, Taylor B. Cavazos, Jieyang Wang, Jeremy Ku, Alex Degtiar, Akshaya Krishnan, Martha Hernandez, Alice Huang, Selina Chen, Dang Nguyen, Ti Lam, Rose Hanna, Lisa Fish, Magdalena Gebala, Alexx J. Smith, Sukh Sekhon, Jennifer Yen, Jeff Gregg, Hani Goodarzi, Helen Li, Fereydoun Hormozdiari, Babak Behsaz, Anna Hartwig, Lee Schwartzberg, Babak Alipanahi. Detection of early stage colorectal cancer using cell-free oncRNA biomarkers and AI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7133.

Breast cancer is common among women in the US and can impact survivors’ quality of life (QoL). Perceived discrimination, defined as unfair treatment based on group membership, is often associated with poorer QoL, while effective patient-provider communication is often linked to better QoL. However, whether communication can mitigate the negative effects of discrimination remains unclear. This study investigates the relationship between perceived discrimination and QoL among women with early-stage breast cancer, and the potential mediating role of patient-provider communication. We analyzed baseline survey data from women with early-stage breast cancer enrolled in a randomized control trial. Validated instruments were used to measure perceived discrimination, patient-provider communication, and mental and physical QoL. We used linear regression to assess the association between discrimination and outcomes (QoL and patient-provider communication), and mediation analysis to evaluate if patient-provider communication mediated the relationship between discrimination and QoL. Among 303 women surveyed, 35.6

BACKGROUND:Febrile neutropenia (FN) is a common complication with myelosuppressive chemotherapy regimens, significantly affecting patients with breast cancer (BC) receiving docetaxel and cyclophosphamide (TC). Treatment with granulocyte colony-stimulating factor (G-CSF) is established for prophylactic and therapeutic use to reduce risk of FN. Eflapegrastim-xnst, a novel long-acting G-CSF, has a favorable safety profile and is effective in reducing neutropenia risk in patients with early-stage BC receiving TC, when administered 24 h after chemotherapy. The benefits of eflapegrastim-xnst given same day as TC have not been evaluated in a randomized controlled trial. PATIENTS AND METHODS:This phase 1, multicenter, open-label trial evaluated efficacy and safety of eflapegrastim-xnst administered 0.5 h post-TC chemotherapy for four cycles in patients with early-stage BC. The primary end point was time to recovery of absolute neutrophil count (ANC) from nadir to ≥1.5 × 109/L in cycle 1. Secondary end points included safety, duration of severe neutropenia, incidence of FN, and neutropenic complications. RESULTS:Of 53 patients enrolled, 49 completed the study. Mean time to ANC recovery in cycle 1, the primary end point, was 1.8 days. Only 1 patient (2%) experienced an FN episode in cycle 1 (1 episode/228 cycles received [0.4%]). Incidence of severe neutropenia decreased from 42.9% (cycle 1) to 27.3% (cycle 4). Eflapegrastim-xnst was well tolerated; common treatment-emergent adverse events included fatigue, nausea, alopecia, and bone pain. CONCLUSIONS:Eflapegrastim-xnst, administered same day as TC chemotherapy was effective and well tolerated evidenced by short time to neutrophil recovery and low incidence of FN, with an adverse event profile similar to that of next-day dosing.

PURPOSE:Colorectal cancer is the second leading cause of cancer-related deaths worldwide, and early detection significantly improves treatment outcomes, but existing blood-based tests often have limited sensitivity in early-stage disease. We developed a blood-based test combining orphan noncoding RNAs (oncRNA), a group of small cell-free RNAs, with generative artificial intelligence to detect colorectal cancer. EXPERIMENTAL DESIGN:We leveraged a cohort of 613 colorectal cancer cases and controls to train a model that demonstrated both high clinical performance and minimal technical variability in robustness testing. We further validated our model in an independent, single-source cohort of 192 colorectal cancer cases and controls. Model performance was assessed by sensitivity, specificity, and area under the ROC curve, with attention to early-stage detection. RESULTS:In our independent validation set, we achieved an overall sensitivity of 89% at 90% specificity, with an 80% sensitivity for stage I-an important milestone, as early-stage colorectal cancer detection remains a challenge for other blood-based technologies. Performance was consistent across demographic subgroups. CONCLUSIONS:Our oncRNA-based blood test, powered by artificial intelligence, offers strong performance for early colorectal cancer detection, including in stage I disease for which existing blood-based assays are limited. These findings support further development toward a minimally invasive colorectal cancer screening tool.

Introduction: Patients (pts) with early-stage breast cancer (ESBC) receiving docetaxel and cyclophosphamide (TC) chemotherapy have a high risk of severe neutropenia (SN) and febrile neutropenia (FN) that can increase the risk of life-threatening infections and lead to chemotherapy dose reductions or treatment delays. The National Comprehensive Cancer Network recommends prophylactic treatment with granulocyte colony stimulating factor (GCSF) to reduce the risk of FN. Eflapegrastim is a novel long-acting GCSF consisting of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a short polyethylene glycol linker. Eflapegrastim, via transcytosis and recycling, demonstrates increased bone marrow residence compared with pegfilgrastim, potentially improving its bioavailability following chemotherapy and allowing same-day dosing. Same day dosing has the potential to improve pt convenience by reducing multiple office visits. In the phase 3 pivotal trials ADVANCE (NCT02643420) and RECOVER (NCT02953340), eflapegrastim was administered ∼24 hours post TC administration. Both studies showed non-inferiority of eflapegrastim to pegfilgrastim in reducing the duration and incidence of neutropenia in pts with ESBC receiving TC. In this study, we evaluated the safety of same-day dosing of eflapegrastim in the same disease setting. Methods: This multicenter, open-label study (NCT04187898) enrolled pts with confirmed ESBC (stage I to IIIA), aged ≥ 18 years who were candidates for neoadjuvant or adjuvant TC. Pts received subcutaneous eflapegrastim (single, fixed dose of 13.2 mg [3.6 mg GCSF]) 0.5 h ± 5 min post TC (intravenous docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2) The primary endpoint was the time to recovery of absolute neutrophil counts (ANC) from nadir to ≥ 1.5×109/L in C1. Secondary endpoints included incidence of SN (ANC < 0.5×109/L) and FN (ANC < 1.0×109/L and temperature of > 38.3 oC or 2 consecutive readings ≥ 38.0 oC over 2 hours), duration of SN (DSN), and incidence of neutropenic complications, including use of antibiotics and/or hospitalizations. Blood samples for complete blood counts with differential were collected pretreatment and on day 1 and daily on days 4–10 of C1. Safety assessments began with the first dose of TC and lasted until 35 ± 5 days after the last dose of eflapegrastim. Here, we report the treatment-emergent adverse events (TEAEs) of interest. All results reported are descriptive. Results: A total of 53 pts (mean [SD] age: 62.7 [11.9] years; female: 100%) from 13 sites across the US, were enrolled (White: 62.3%; Black or African American: 9.4%; others: 28.3%). Pts were relatively healthy (ECOG 0, 52.8% [n = 28] patients; ECOG 1, 47.2% [n = 25] patients). Efficacy in C1 was evaluable in 49 patients. Mean (SD) time to ANC recovery was 1.8 (1.1) days. Incidence of SN was 46.9% (n = 23) and mean (SD) DSN was 0.8 (1.0) days. Incidence of FN was 2% (n = 1). No neutropenic complications were observed during the study. Safety was assessed in all 53 patients who received at least 1 dose of eflapegrastim. Overall, 43 patients (81.1%) experienced any TEAE of musculoskeletal pain. Common musculoskeletal-related TEAEs experienced by ≥ 10% of patients were bone pain (52.8%; n = 28); back pain (26.4%; n = 14), arthralgia or pain in extremity (17.0%; n = 9 for each); and myalgia (13.2%; n = 7). No deaths were reported during the study. Conclusions: These findings suggest that administration of eflapegrastim on the same day as TC chemotherapy may be advantageous in reducing the time to ANC recovery and related complications in pts with ESBC. The AEs observed in this study were consistent with those generally observed in pts receiving TC and other GCSF products. Funding: This study was funded by Assertio Pharmaceuticals, Inc. Disclosures: MM and JLV have no conflicts to disclose. OM has received personal fees for consulting and research funding from OnQuality Pharmaceuticals. SC was an employee of Spectrum Pharmaceuticals, Inc. and still holds shares in Assertio Holdings, Inc. as a result of Assertio’s acquisition of Spectrum. KC and HF are employees of Assertio Holdings, Inc. LS has received personal fees for consulting from Assertio Holdings, Inc., and Coherus Biosciences. Citation Format: Manuel Modiano, Omkar Marathe, Shanta Chawla, Jeffrey L. Vacirca, Kenneth Crist, Howard Franklin, Lee Schwartzberg. Eflapegrastim, a long-acting GCSF, administered the same day as chemotherapy in patients with early-stage breast cancer: Results from a multicenter, open-label, study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-10-22.

Adjuvant endocrine therapy (AET) improves survival in hormone receptor-positive breast cancer, yet adherence is often lower among individuals with limited health literacy. This post hoc analysis of the THRIVE trial examined whether health literacy modified the effectiveness of two remote monitoring interventions (App-only and App + Feedback) versus enhanced usual care (EUC) on 12-month AET adherence (≥80 % of prescribed doses via connected pillbox). Among participants with lower health literacy, adherence was higher with App + Feedback than EUC (80.0 % vs. 42.1 %, p = 0.03), with no significant differences among those with higher health literacy. Tailored digital interventions may support adherence among patients with limited health literacy. TRIAL: ClinicalTrial.gov identifier NCT03592771.

BACKGROUND:Adjuvant endocrine therapy (AET) reduces the risk of breast cancer recurrence, but racial differences in nonadherence persist, potentially reflecting variations in symptom burden. We conducted a post hoc analysis of the THRIVE trial to investigate symptom burden and AET adherence by race among women with early-stage breast cancer. PATIENTS AND METHODS:We included Black and White women who enrolled in the THRIVE trial, a remote monitoring intervention, from November 2018 to June 2021. Participants completed surveys at baseline and at months 6 and 12, including symptom burden measured using the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) instrument. Adherence was defined as the proportion of days covered >80% using an electronically monitored pillbox. Multivariable regression analyses were performed to examine factors associated with adherence, and Kitagawa-Oaxaca-Blinder decomposition was used to quantify the proportion of adherence differences explained by symptom and patient characteristics. RESULTS:Among 102 (34.7%) Black and 192 (65.3%) White women randomized to 3 study arms evaluating the efficacy of the remote monitoring intervention, 84% completed the 6-month survey, and 87% completed the 12-month survey. Black participants were younger and had lower income and health literacy (P<.01). Black women reported worse symptoms at baseline (60.9 vs 64.4; P=.003) and month 12 (57.0 vs 61.9; P<.001), yet a similar proportion experienced 5-point decreases (the minimally important difference) over the 12-month period (34.9% vs 32.4%; P=.69), compared with White women. At month 12, fewer Black participants were adherent to AET than White participants (43.0% vs 60%; difference=17.0 percentage points [ppts]; P=.009). This difference was attenuated after adjusting for symptoms and patient characteristics (-7.75 ppts; P=.34). Baseline symptoms (0.77 ppts; P=.021) were significantly associated with adherence over 12 months, whereas changes in symptoms were not (0.14 ppts; P=.69). Symptom and patient characteristics together accounted for 58% of the 1-year adherence difference between racial groups. CONCLUSIONS:Black women had lower 1-year AET adherence compared with White women, largely attributed to baseline symptoms and sociodemographic characteristics. More proactive symptom management and addressing social determinants of health among Black women may alleviate disparities in AET adherence. CLINICALTRIALS:gov Identifier: NCT03592771.

Background: Cancer therapy-related diarrhea (CTD) is a common adverse effect of targeted therapies (e.g., TKIs, CDK4/6 inhibitors), resulting in treatment modifications and poor clinical outcomes. Yet, longitudinal patterns of CTD’s impacts on cancer therapy (e.g., dose reductions, delays, and/or discontinuation) remains poorly characterized. Here we present patient reported outcomes (PRO) data on the incidence and severity of diarrhea in adult patients with breast cancer receiving abemaciclib and pertuzumab-based therapies in the placebo arm of the OnTarget study (NCT04538625). Methods: OnTarget was a randomized, multicenter, double-blind, placebo-controlled prophylactic trial evaluating crofelemer versus placebo in adults with solid tumors receiving targeted therapies with or without standard chemotherapy. Patients were randomized to crofelemer or placebo given orally twice daily for 12 weeks. PRO-based diarrhea events were captured real-time using a mobile device. Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and antidiarrheal or antibiotic use ≤7 days. PRO grading used The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for the number of loose/watery stools (LWS)/day using the Briston Stool Form Scale (6 or 7) for grades 1-4 of diarrhea. The incidence of diarrhea was evaluated as the proportion of days with LWS for each 21-day period of the 84-day treatment period. The proportion of patients requiring targeted therapy or chemotherapy dose modifications, including reductions, interruptions or discontinuations, were evaluated over each 21-day period. The proportion of patients using antimotility drugs as rescue medications for each cycle were also evaluated. Results: The OnTarget study enrolled 287 adults with 10 solid tumor types and 24 unique targeted therapies. Patients were randomized 1:1 to placebo (n=142) or crofelemer (n=145) to prevent diarrhea. The safety population of patients with solid tumors randomized to the placebo arm was 135. The median age was 59 yrs [IQR: 51-57 yrs], 18.5% non-White). PRO data on diarrhea were available for 126 patients with different solid tumors over the 12-week period. Specifically, 81 (57%) were patients with breast, 18 (12.7%) lung, 14 (9.9%) renal, 9 (6.3%) liver, and 4 (2.8%) gastrointestinal cancers in the placebo group. Kinase inhibitors were administered to 49 (38.9%) patients with lung, renal, liver, breast and gastrointestinal cancers; two cohorts of patients with breast cancer received abemaciclib [n=44; 34.9%] and pertuzumab-based therapies with chemotherapy [n=29; 23%]. Abemaciclib patients experienced their maximum grade diarrhea during days 22-42 of their treatment, with a median of 7.1 LWS/week (IQR: 3.1-10.4). Over the 12-week, abemaciclib treatment period, a total of 18 (43.9%) patients with breast cancer required a dose modification due to diarrhea, and 24 (58.5%) reported rescue loperamide use. In contrast, those receiving pertuzumab/trastuzumab/docetaxel and carboplatin [n=17] had maximum median grade diarrhea during cycle 1 with 7.1 LWS/week (IQR: 4.6-12.3), and 75% of these patients reported rescue loperamide use. For the 4-cycle period for this pertuzumab cohort, the median LWS/week was 6.19 (IQR: 3.3-8.4), with all patients requiring a dose modification and 88.2% reporting rescue loperamide use. Conclusion: This PRO-based prophylactic study on the incidence of diarrhea in patients with breast cancer receiving abemaciclib or pertuzumab-based therapies with standard chemotherapy over a 12-week period showed that most patients with breast cancer required dose modifications due to diarrhea and/or used rescue medications to remain on their cancer therapy. The use of real-time PRO data on CTD in adult patients with breast cancer shows that diarrhea remains a neglected and under-reported comorbidity of cancer treatment. Citation Format: Pablo C. Okhuysen, Eric Roeland, Lee Schwartzberg, Hope Rugo, Stacy Tinianov, Kelly Shanahan, Enoch Bortey, Jim Bolognese, Pravin Chaturvedi. Natural history including the incidence, severity and management of diarrhea in patients with breast cancer receiving abemaciclib and pertuzumab-based therapies with or without standard chemotherapy: Data from placebo arm of the OnTarget study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-02-15.

BACKGROUND:Overall survival (OS) is the gold standard for assessing clinical benefit in oncology but requires extended follow-up to detect sufficient events. Invasive disease-free survival (iDFS) requires shorter follow-up times and is considered an objective and clinically meaningful end point in early breast cancer (EBC) trials. The authors assessed iDFS as a surrogate end point for OS in adjuvant HR+/HER2- EBC using real-world patient-level data. METHODS:A retrospective analysis was conducted on patient data from the ConcertAI Patient360 database (January 1995-April 2021). Key inclusion criteria: age ≥18 years, stage II or III (AJCC 8th Edition) HR+/HER2- EBC, prior surgery, adjuvant endocrine therapy (ET). Spearman ρ, iterative multiple imputation ρ (IMI; 0.8-1 considered "very strong"), and R2 (clinical relevance R2 ≥ 0.70) were used to assess iDFS-OS relationship. Subgroup analyses included ET (nonsteroidal aromatase inhibitor or tamoxifen), stage, menopausal status, nodal status, prior (neo)adjuvant chemotherapy, and prior radiotherapy. RESULTS:A total of 3133 patients were included (1103 [35.2%] iDFS events; 554 [17.7%] OS events); mean age was 58.4 years, 98.8% were female, 29.9% were premenopausal, and 80.9% had stage II disease. Median follow-up time was 55.1 months. iDFS and OS exhibited a positive, very strong, clinically relevant correlation (Spearman ρ: 0.88 [0.87-0.89]; IMI ρ: 0.83 [0.79-0.86]; both p < .0001). iDFS accounted for 82% of variation in OS (R2 = 0.82). Results of all subgroup analyses were consistent with overall population. CONCLUSIONS:This patient-level real-world analysis demonstrated very strong, positive correlations between iDFS and OS, supporting the use of iDFS as a reliable primary end point in adjuvant HR+/HER2- EBC.

Background: Cancer therapy-related diarrhea (CTD) is a common adverse effect of targeted therapies (e.g., TKIs, CDK4/6 inhibitors), resulting in treatment modifications and poor clinical outcomes. Crofelemer is a chloride ion channel modulator of cystic fibrosis transmembrane conductance regulator. It is FDA-approved for HIV-associated diarrhea based on a responder analysis of the proportion of patients with improved diarrhea. Here, we present the prespecified responder analysis of the OnTarget study (NCT04538625) in the breast cancer subgroup receiving targeted therapies. Methods: OnTarget was a randomized, multicenter, double-blind, placebo-controlled prophylactic trial evaluating crofelemer versus placebo in adults with solid tumors receiving targeted therapies. Patients were randomized to 125 mg of crofelemer twice daily or placebo for 12 weeks to prevent CTD. Diarrhea outcomes were captured using patient-reported outcomes (PROs). Key exclusions included immunotherapy, neratinib, irinotecan, colitis/ostomy/abdominal surgery ≤3 months, and any antidiarrheal or antibiotic use ≤7 days. The primary outcome was the mean weekly number of loose/watery stools (LWS) over 12 weeks. Secondary endpoints included the Patient Global Impression of Severity (PGIS) for gastrointestinal symptoms, and time to onset of durable response. Subgroup analyses for tumor types and targeted therapies were prespecified; anchor-based methods using PGIS determined optimal thresholds for the average number of weekly LWS for responders. The optimal cut-off values of the mean LWS per week to define responders were derived via receiver operating characteristics (ROC) curve analyses of PGIS anchors. Further, monthly responders met the cutoff for mean weekly LWS for at least 2 of 4 weeks per month. Since the time to onset of responder status does not address sustainable effects, continuous efficacy over the entire 3-month period was assessed per ordered categories (none, 1/3, 2/3, or 3/3 months) via ordered logistic regression. We analyzed the onset and sustained effect of treatment using response patterns that prioritized an early and durable response for each month. The patterns of the number of responding months were ranked from 0-8, with a rank of 8 designating a full responder for all 3-months. All p values are 1-sided. Results: The OnTarget study enrolled 287 adults with 10 solid tumor types and 24 unique targeted therapies. The prespecified primary endpoint of the mean weekly LWS over 12 weeks was not met. Adverse events were similar in both arms. A total of 184 (64.1%) patients with breast cancer participated; median age 57 yrs [IQR: 48-65 yrs], 16.5% non-White); 96 (54.6%) received abemaciclib, 67 (38.1%) pertuzumab/trastuzumab, and 13 (7.4%) kinase inhibitors. PRO data was available for 176 patients with breast cancer. ROC analysis showed that weekly responders have ≤9 LWS/week in each week. Continuous responder efficacy analysis in patients with breast cancer having ≤9 LWS/week showed significant improvement with crofelemer over placebo (OR 1.77 [CI: 1.01-3.12]; p=0.0245). Patients with an ECOG performance status of 0-1 (n=170) showed improved response with crofelemer compared to placebo (OR 1.99 [95% CI: 1.11-3.56]; p=0.0104). Additionally, more patients with breast cancer receiving crofelemer (41/87; 47.1%) were responders for all 3 months compared to placebo (30/89; 33.7%) (OR 2.14 [95% CI: 1.10-4.14]; p=0.0123). Crofelemer had significantly faster onset and sustained efficacy compared to placebo (OR 1.80 [95% CI: 1.02-3.16]; p=0.021), including patients with ECOG status of 0-1 (n=170, OR 2.00 [95% CI: 1.12-3.56]; p=0.0095). Conclusion: In this responder analysis of patients with breast cancer on targeted therapies, crofelemer CTD prophylaxis resulted in a greater proportion of monthly responders of diarrhea improvement compared to placebo, with better-sustained response in those with preserved functional status (ECOG 0-1). Citation Format: Pablo C. Okhuysen, Eric Roeland, Lee Schwartzberg, Hope Rugo, Enoch Bortey, James Bolognese, Stacey Tinianov, Kelly Shanahan, Pravin Chaturvedi. OnTarget crofelemer diarrhea prophylaxis trial: responder analysis of patients with breast cancer receiving targeted therapy with or without chemotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-05-14.

e13108 Background: Antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) have revolutionized breast cancer (BC) treatment, delivering superior efficacy that allows for extended treatment durations. Nausea and vomiting (NV) are among the most frequent adverse effects associated with T-DXd and SG. Persistent nausea can significantly impact patients, negatively affecting their quality of life leading to treatment interruptions, delays, or dose adjustments with potential impact on treatment outcomes. With limited real-world data on ADC dose-intensity adjustments due to NV, surveys of healthcare providers (HCPs) were conducted to assess their experience. Methods: At the 2024 SABCS and 2024 ESMO Congress, HCPs were recruited to complete a short web-based survey in the exhibit hall. Eligible participants included HCPs who used ADCs in clinical practice or clinical trials and were caring for patients with solid tumors. Participants were asked, “How often have you implemented an adjustment (see Table) to ADC treatment due to NV?” Responses included “never,” “rarely,” “sometimes,” “often,” and “always.” Results: A total of 288 HCPs were eligible and participated (90 at SABCS and 198 at ESMO). Most (77%) were oncologists who treated patients with BC. Participants had the most experience with T-DXd and SG. Approximately a third of HCPs had at least sometimes implemented an ADC dose reduction or delay due to NV, while a quarter reported interrupting or discontinuing ADC treatment (Table). Over half of HCPs at least sometimes use rescue medication for NV. Conclusions: Given the increased prominence of ADCs for the treatment of advanced BC, these real-world findings underscore the critical need to optimize NV prevention to reduce dose adjustments or discontinuation. Guideline-recommended NK1 receptor antagonist-based antiemetic prophylaxis may optimize ADCs’ uninterrupted dosing and therapeutic potential. Prospective studies assessing maintenance of dose intensity with optimal antiemetics are needed. SABCS + ESMON = 288 SABCS + ESMON = 288 SABCS only*N = 90 SABCS only*N = 90 SABCS only*N = 90 Implemented Due to Nausea/Vomiting ADC Dose Reduction ADC Dose Delay ADC Dose Interruption ADC Discontinuation Use of Rescue Medication Always 1% 1% 0% 0% 1% Often 6% 5% 8% 6% 16% Sometimes 33% 26% 18% 18% 40% Rarely 35% 36% 42% 31% 34% Never 25% 33% 32% 46% 9% *not asked in the ESMO survey.

OBJECTIVE:To examine the association between COVID-19-related hardship and 1-year adjuvant endocrine therapy (AET) adherence among women with early-stage hormone-receptor-positive breast cancer. STUDY SETTING AND DESIGN:This post hoc analysis utilized data from the THRIVE trial, which tested a 6-month remote monitoring intervention on 1-year AET adherence, measured using an electronic pillbox. The 1-year follow-up survey included questions about pandemic-related hardship, including financial loss, changes/gaps in health insurance, and difficulty accessing basic needs. Participants reporting any of these were categorized as experiencing pandemic-related hardship. Logistic regressions estimated the association between patient characteristics and pandemic-related hardship, and between hardship and AET adherence (≥ 80% proportion of days covered), controlling for patient characteristics and randomization group. DATA SOURCES AND ANALYTIC SAMPLE:We included 217 women diagnosed with early-stage breast cancer prescribed AET at a large cancer center who enrolled in THRIVE between April 2019 and June 2021. PRINCIPAL FINDINGS:Overall, 39.6% of participants reported any pandemic-related hardship: 34.6% reported financial loss, 10.6% reported changes/gaps in insurance, and 11.1% reported difficulty accessing basic needs. In adjusted analyses, having an income ≤ 100% of federal poverty level or prior chemotherapy or radiation was associated with a 41.4 (95% CI: 9.8-73.0) and 13.8 (95% CI: 0.3-27.2) percentage-point higher likelihood, respectively, of having any pandemic-related hardship. Over half (52%) of participants were AET adherent. In adjusted analyses, 40.1% of those with any pandemic-related hardship were AET adherent, compared with 59.5% of those without hardship, a 19.3 percentage-point lower likelihood (95% CI: -33.0 to -5.7). CONCLUSIONS:Pandemic-related hardship was more common among individuals with lower income or prior radiation or chemotherapy, and was associated with lower AET adherence, with possible impacts on cancer progression and survival. These findings highlight the need for routine financial screening and targeted support, particularly among lower-income patients on long-term AET. TRIAL REGISTRATION:NCT03592771.

e13679 Background: Clinical trial populations are not typically ethnically diverse, restricting healthcare equity and the generalizability of clinical trial data to real-world populations. Moreover, mostpatients (pts) with cancer in the US receive treatment in the more diverse community setting, where minority groups are usually better represented but with lower trial enrollment rates than academic centers. MyTACTIC (NCT04632992) is a phase II, non-randomized basket trial evaluating targeted therapies in pts with advanced solid tumors with specific biomarkers. Inclusive research practices, including mostly community recruitment, were implemented in MyTACTIC to improve access for patients who may otherwise not have been able to enroll. This retrospective analysis presents their impact on the diversity of the trial population. Methods: Adult pts with advanced solid tumors were enrolled from community cancer clinics (private practices and community hospitals) or large academic centers, into 1 of 15 arms based on biomarker alterations. Inclusive research practices implemented to diversify pt recruitment included: revision of eligibility requirements to be more inclusive for minorities; language simplification and streamlining of study protocol; training activities; free transportation. We compared race and ethnicity data between the study population and trial sites’ catchment area (geographical area of pts around the clinical site). Results: Forty pts, all of White race, were initially enrolled across 14 sites, which prompted additional focus on diversity efforts. The trial was expanded to 45 sites across 21 states: 252 pts were enrolled (83% of White race) (Table). Most (96%) selected sites (n=249 pts) were community clinics. The proportion of pts from racial minorities was generally higher in study centers from ethnically diverse catchment areas. Protocol streamlining and staff training were also beneficial to pt recruitment. Free-ride transportation removed the barrier of access to clinical trial sites. The impact of other initiatives will be presented. Conclusions: Running clinical trials at community oncology sites does not, in itself, equal increased diversity of study populations: other efforts, including but not limited to free transportation and community site selection, are also needed. Here we share some learnings from the MyTACTIC study, based on outcomes from the various inclusive research practices implemented in this trial. Clinical trial information: NCT04632992 . [Table: see text]

Abstract Background: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence, but racial differences in nonadherence remains a concern. Differential symptom burden may contribute to disparities in AET adherence. Method: We conducted a post hoc analysis by race among women with breast cancer starting AET who were randomized in THRIVE Study (NCT03592771) to investigate remote symptom monitoring intervention vs. usual care from 11/2018 to 06/2021. Participants completed surveys at baseline, 6- and 12-month. Outcomes were symptom burden measured by FACT-Endocrine Subscale, and adherence measured by electronically monitored pillbox (>80% Proportion of Days Covered). We estimated symptom differences by race using linear regression with and without adjusting for baseline characteristics. To examine whether symptom burden contributed to racial differences in adherence, we conducted multivariable regression for adherence with and without controlling for symptom burden, and Blinder-Oaxaca decomposition. Results: Among 102 (34%) Black and 194 (66%) White women who were randomized, retention was 88% at 12-month. Compared to White participants, Black participants were younger (55 vs. 60 years), more likely to be at poverty (10.8% vs. 4.1%), and had lower health literacy (18.9% vs. 13.4%; p-values<.01). While symptom burden did not differ by study arm, Black participants had worse symptoms than White at baseline (60.8 vs. 64.5, p=.002). This gap became smaller at 6-month (59.7 vs. 61.2, p=.30), but diverged again at 12-month (56.9 vs. 61.8, p<0.01). Differences at 12-month diminished after controlling for baseline characteristics (-1.6, 95%CI=-4.4 to 1.2). Notably, being at poverty and younger age were associated with higher symptoms. Adherence was lower among Black participants at 6-month (0.69 vs. 0.78, p=.13) and 12-month (0.44 vs. 0.60, p=.014) than White participants. Unadjusted differences in adherence at 12-month (-16.0 percentage points [ppts], 95%CI=-28.9 to -3.3, p=.01) attenuated after adjusting for baseline symptoms, symptom changes to 12-month, and other baseline characteristics (-10.4 ppts, 95%CI=-25.6 to 4.8, p=.18). Lower baseline symptoms were associated with better adherence (0.8 ppts, 95%CI=0.1 to 1.4, p=.03). Decomposition indicates that 9.1 ppts (95%CI=-4.8 to 23.0, 57%) of the difference in 12-month adherence was explained by symptoms and baseline characteristics, and remaining unexplained difference was 6.9 ppts (95%CI=-12.6 to 26.4, 43%). Conclusion: Our results add to increasing evidence that Black women with breast cancer have lower AET adherence, which may be partially attributed to worse symptoms than White women. These results highlight the need for new strategies to promote equitable symptom management and adherence strategies between Black and White women to reduce disparities in outcomes. Citation Format: Xin Hu, Rebecca A. Krukowski, Ed Stepanski, Lee S. Schwartzberg, Gregory A. Vidal, Ilana Graetz. Race differences in symptom burden and medication adherence among women with breast cancer on adjuvant endocrine therapy: A post hoc analysis of a randomized control trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4836.