Contemporary real-world data on treatment patterns and clinical outcomes in patients with programmed death ligand 1 (PD-L1)-negative locally recurrent inoperable or metastatic triple-negative breast cancer (lr/mTNBC) are sparse. We describe first-line (1L) systemic therapies and real-world survival outcomes in this population in the United States (US). Adults with PD-L1-negative lr/mTNBC initiating 1L systemic treatment in the US were identified using the Komodo Research Data (KRD+; 1/1/2016-12/31/2023). Treatment patterns, including treatment durations and sequences from 1L through three lines of therapy, real-world overall survival (rwOS) and progression-free survival (rwPFS) from 1L, were analyzed. rwOS and rwPFS were summarized using Kaplan-Meier methods in subgroups of patients with ≥ 18 months and ≥ 6 months of potential follow-up, respectively. Overall, 929 patients were included (median age 59.0 years, 60.1

BACKGROUND:Tumor-infiltrating lymphocytes (TILs), assessed by visual examination, are prognostic and predictive in early-stage triple-negative breast cancer. Computational assessment may provide a complementary approach. We evaluated the prognostic value of TILs by visual examination and computational assessment. METHODS:Cisplatin vs Paclitaxel for Triple Negative Breast Cancer (TBCRC030; ClinicalTrials.gov identifier NCT01982448) was a randomized phase 2 trial enrolling patients with BRCA1/2-proficient stage I to III triple-negative breast cancer to receive preoperative cisplatin or paclitaxel. The primary endpoint was pathological response at surgery. The TILs were visually scored on digitized pretreatment biopsies per International TILS Working Group recommendations. Computational assessment used the 4D Path QPOR platform to generate TILs, an immune heterogeneity index, and a combined immune/cell cycle biomarker (CmbI). Predictive performance for residual cancer burden 0/1 was assessed using receiver operating characteristic curves and odds ratios (ORs) with 95% CIs; all statistical tests were 2-sided. RESULTS:Of 139 response-evaluable patients, 121 had matched visual examination and computational assessment data (59 on cisplatin, 62 on paclitaxel). Median visual examination TILs were higher in responders (40.0% vs. 10.0%; P = .002) and predicted response (OR = 1.86, 95% CI = 1.24 to 2.87; area under the curve = 0.69, 95% CI = 0.57 to 0.80). Computational assessment CmbI differed by response group and predicted residual cancer burden 0/1 (OR = 3.20, 95% CI = 1.05 to 11.07; area under the curve = 0.62, 95% CI = 0.51 to 0.73). Computational assessment TILs and immune heterogeneity index were not predictive. Visual examination TILs and computational assessment CmbI predicted response to paclitaxel (OR = 2.91, 95% CI = 1.56 to 6.14; OR = 9.17, 95% CI = 2.01 to 66.39, respectively) but not to cisplatin. CONCLUSION:Visual examination TILs and computational assessment CmbI were each associated with response to neoadjuvant chemotherapy in triple-negative breast cancer in the overall cohort and the paclitaxel arm. Computational assessment CmbI did not outperform visual assessment. Further validation is needed before clinical implementation of computational approaches.

TPS1680 Background: Telehealth (TH) use for cancer care has rapidly expanded, both during and following the COVID-19 pandemic. However, evidence regarding safety, feasibility, effectiveness, equity, stakeholder satisfaction, and implementation of telehealth-enabled oncology care remains limited. We seek to assess the impact of TH on these outcomes in breast and prostate cancer patients. Methods: The MATCH-UP pragmatic cluster randomized trial is being conducted at Memorial Sloan Kettering Cancer Center to compare alternate models of TH use in oncology practice. Sixty-two physician practice clusters in breast and prostate medical oncology are randomized 1:1 to enhanced telehealth (ET) or usual practice (UP), stratified by disease type and clinic volume. ET emphasizes TH with expanded home services designed to deliver as many components of care as desired in patients’ homes. Usual care involves routine practice with TH visits at the discretion of the patient and MD or APP. Eligible patients have >=3 prior medical oncology visits and are not enrolled on a therapeutic trial. Automated enrollment is triggered by a routine oncology visit with waiver of informed consent. The ET intervention includes EHR-enabled telehealth scheduling defaults for routine follow-up visits, optional home phlebotomy, structured support for home administration of select injectable medications, and digital support for patients with TH access barriers. The primary endpoint is the proportion of routine medical oncology visits conducted in person among all routine medical oncology visits over 1 year. Secondary outcomes include healthcare utilization, no-show and late cancellation rates, and overall survival. Patient-reported outcomes include: quality of life, healthcare costs, experience of care, and preferences for use of TH at future visits. Clinician-reported outcomes include: experience of care and preferences for TH use at future visits. For patients in the ET arm only, telehealth accessibility, intervention uptake and efficiency, and implementation outcomes, including acceptability, appropriateness, and feasibility, are also being collected. The primary endpoint will be analyzed using generalized linear mixed models with a logistic link, accounting for repeated visits within patients and clustering within randomized practice units and adjusting for stratification factors. Enrollment will continue through March 2026 with follow-up for 12 months. To date, 7256 patients have been enrolled, with 3641 patients assigned to ET, (n=2437 [67%] breast cancer; n=1204 [33%] prostate cancer and 3,615 assigned to UP (n=2252 [62%] breast cancer; n=1363 [38%] prostate cancer). MATCH-UP will generate pragmatic evidence on the effectiveness, patient-centeredness, implementation, and equity-relevant barriers of a scalable, EHR-embedded enhanced telehealth model for breast and prostate oncology care. Clinical trial information: NCT06954337 .

PURPOSE:To examine real-world treatment patterns and effectiveness among patients with metastatic triple-negative breast cancer (mTNBC) in the United States. DESIGN:Retrospective, observational study using Flatiron Enhanced Datamart electronic health records from patients diagnosed with mTNBC between January 1, 2018, and June 30, 2023, who received ≥1 line of therapy (LoT) for metastatic disease. Patients were followed until date of death, last recorded activity, or data cutoff (December 30, 2023). Patient characteristics, treatments received from LoT1-5, and clinical outcomes (overall and by LoT) were described. RESULTS:The cohort comprised 1,044 patients. Most were female (99.2%); the median age was 61 years (IQR, 52-71); 52.1% were White and 21.7% were Black. The most common drug class in all LoTs was chemotherapy, as monotherapy or in combination with other agents: LoT1 85.5%, LoT2 73.2%, LoT3 65.8%, LoT4 64.7%, and LoT5 71.7%. Among patients with known PD-L1 status (n = 367), 109 (29.7%) were PD-L1-positive and 258 (70.3%) were PD-L1-negative. For the overall cohort, the median real-world overall survival (rwOS) from diagnosis was 14.0 (95% CI, 12.9 to 16.0) months. Real-world progression-free survival was 4.5 (95% CI, 4.0 to 5.0) months in LoT1 and 4.1 (95% CI, 3.5 to 4.9) months in LoT2. The median rwOS was 18.6 (95% CI, 15.2 to 24.4) months in the PD-L1-positive cohort versus 12.7 (95% CI, 11.0 to 16.0) months in the PD-L1-negative cohort. From December 1, 2021, onward, immunotherapy was received in LoT1 by 63.6% (21/33) of patients who had PD-L1-positive tumors and by 84.6% (33/39) of patients with PD-L1-positive tumors across all LoTs. CONCLUSION:Real-world clinical outcomes in patients with mTNBC in the United States remain poor, particularly for patients with PD-L1-negative disease. There is an unmet need for more effective treatments for mTNBC.

TPS1162 Background: Triple-negative breast cancer (TNBC) refers to a heterogenous group of breast cancers that lack expression of ER, PR, and HER2. Despite recent advances with immunotherapy (IO) and antibody-drug conjugates (ADCs), TNBC remains the most aggressive subtype, with short overall survival in the metastatic setting. Breast tumors with low levels of ER and PR expression (1-10%) clinically behave like TNBC, and clinical management follows the TNBC treatment (tx) paradigm. We and others have identified a subset of ER/PR/HER2-negative breast cancers (BCs) that express the androgen receptor (AR). Enzalutamide (enza), an AR-antagonist, has demonstrated activity in AR-positive metastatic TNBC (Traina et al, JCO 2018). Activation of the glucocorticoid receptor (GR) has been implicated as a mechanism of resistance to AR inhibition in prostate and BCs (Kach et al, Sci Transl Med 2015). Effective therapies for advanced TNBC remain an unmet need, particularly in patients who are ineligible for or progress following a checkpoint inhibitor. This randomized study evaluates the efficacy of enzalutamide or enzalutamide plus the GR antagonist mifepristone (mif) as compared to physician’s choice chemotherapy (TPC). Methods: This is a randomized phase II trial; 201 patients (pts) will be randomized in a 1:1:1 fashion to enza, enza with mif, or TPC (carboplatin, paclitaxel, eribulin, or capecitabine). The primary endpoint (endpt) is progression-free survival (PFS), and the trial is designed to test the hypothesis that PFS in the pooled enza arms is superior to TPC; there is 80% power to detect a hazard ratio (HR) of 0.70, corresponding to an increase in median PFS from 3.5 months (mos) with TPC to 5.0 mos with enza-based tx. Secondary endpts include comparisons of PFS among the 3 arms and evaluation of response rate, clinical benefit rate, duration of response, overall survival, safety, and patient-reported outcomes by arm. Exploratory endpts include correlation of tumor and circulating markers (constitutively active AR variants in circulating tumor cells and cfDNA) with tx response. Eligible pts must have: ECOG 0-2, metastatic measurable or evaluable disease (dz), normal organ function, no history of brain mets, < prior lines of chemotx, any # of prior endocrine txs, no prior anti-AR tx, no prior mif, no concurrent CYP17 inhibitor use. Tumors must test ER/PR low or negative, HER2 negative, AR >10%. Pts with PD-L1+ BC must have received prior IO if not contraindicated. As of December 28, 2025, 32 of 201 pts have been enrolled on study. Clinical trial information: NCT06099769 .

Importance Premenopausal patients with breast cancer are treated with gonadotropin-releasing hormone agonist (GnRHa) therapy to suppress ovarian function. Therapy requires subcutaneous or intramuscular injection and is routinely administered during clinic visits. Objective To evaluate the feasibility and acceptability of a telemedicine-supported home-injection program for patients with breast cancer receiving GnRHa therapy. Design, Setting, and Participants This quality improvement study was conducted between October 2024 and August 2025. Patients were followed up for up to 2 home injections over a 6-month period. Patients were recruited from 4 outpatient medical oncology practices at a comprehensive cancer center. Eligible participants were adults with breast cancer who used the patient portal and had ongoing therapy with a GnRHa. Intervention Patients received in-clinic training from nursing staff on injection preparation and administration. Telemedicine nursing visits for supervision of home injections were optional. Main Outcomes and Measures The primary outcome was feasibility, assessed by home-injection completion rates. Patient and clinician satisfaction were assessed using net promotor scores and rates of continued home injection following the pilot. Patients were invited to participate in semi-structured exit interviews. Results Of 105 eligible patients, 54 chose to participate, and 24 obtained coverage to dispense medication for self-injection at home. Among the 24 participants (median [range] age, 44 [33-53] years) all were female. All participants were trained in GnRHa intramuscular administration; 10 of 20 (50.0%) had no prior injection experience. Overall, of the 24 participants, 23 (95.8%) successfully completed at least 1 injection at home, 19 (79.2%) completed 2, and 18 (75.0%) opted to continue home administration beyond the study end. Only 1 patient discontinued due to challenges related to injection administration and telemedicine scheduling. Of 17 patients, time savings (15 [88.2%]) and convenience (13 [76.5%]) were cited as key benefits. The model was strongly endorsed, according to a net promoter score of 69 for patients and of 61 for clinicians. Of the 54 patients who chose to participate, 19 (35.2%) were unable to proceed due to a lack of insurance approval for home administration of the eligible medication, and among 30 patients who received insurance authorization, 18 (60.0%) incurred a copayment for the medication when injection coverage shifted from clinic-based administrations to home-based administrations. Conclusions and Relevance In this quality improvement study of a telemedicine-supported home injection model for women with breast cancer, strong feasibility was demonstrated by high injection completion rates and acceptability by participants. The findings suggest that insurance approval and the copayments associated with at-home, but not in-clinic, administration were an impediment to participation and need to be addressed before scaling.

1581 Background: Among the growing population of premenopausal patients with breast cancer, years-long endocrine therapy often requires repeated clinic-administered injections, creating substantial time burden and adherence challenges. This pilot evaluated the feasibility of a telemedicine-supported home injections program designed to improve access, convenience, and patient experience. Methods: Patients were recruited from 4 outpatient medical oncology practices at a comprehensive cancer center between October 2024 and January 2025. Eligibility criteria included a breast cancer diagnosis, an active treatment plan including leuprolide and/or denosumab, and use of the patient portal. Patients proceeded to pilot participation after insurance approval for outpatient administration of medications and (if applicable) acceptability of copay cost. Patients and/or caregivers received in-clinic training by nursing staff on injection preparation and administration, were provided both written and video-based educational material and were followed for up to 2 home injections over a 6-month period, with telemedicine support. The primary outcome was feasibility, assessed by home injection completion rates. Patient and clinician satisfaction were assessed using the Net Promotor Score (NPS) and rates of continued at home injection administration post pilot completion. Patients were also invited to participate in 60-minute semi-structured exit interviews. Results: Of 105 eligible patients, 54 agreed to participate in the pilot and 24 obtained insurance approval for the medication with an acceptable copay. All 24 patients were trained in injection administration of intramuscular leuprolide, of whom 50% had no prior injection experience. Overall, 96% successfully completed one home injection, 79% of patients completed two home injections, and 75% continued home administration after follow-up. Notably, only 1 patient discontinued home injection administration due to telemedicine scheduling related issues. Patients reported high satisfaction, citing time savings and convenience as key benefits. Both patients and providers strongly endorsed the model with highly compelling net promoter scores of 69 and 61, respectively. Conclusions: This pilot demonstrated the feasibility of a telemedicine supported home injection care delivery model for breast cancer patients in the oncology setting, evidenced by high completion rates and patient preference to continue home administration. Educational materials and optional telemedicine visits for initial injections were leveraged to support adherence without increased healthcare utilization. Further evaluation across broader geographic, demographic, and payor mix is warranted to inform scale up. An ongoing pragmatic trial (NCT06954337) is testing this approach as part of an innovative model of care: Enhanced Telehealth.

1002 Background: In the primary analysis of the phase 3 TROPION-Breast02 study (NCT05374512), first-line Dato-DXd demonstrated statistically significant and clinically meaningful improvements in overall survival (OS; hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.64–0.98]; p = 0.0291) and progression-free survival (PFS; HR: 0.57 [95% CI: 0.47–0.69]; p < 0.0001) compared with investigator’s choice of chemotherapy (ICC) in patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Both median OS and PFS by blinded independent central review (BICR) were ≥5 months longer with Dato-DXd compared with ICC. Moreover, with Dato-DXd vs ICC, the confirmed objective response rate was more than double and median duration of response was > 5 months longer. The Dato-DXd safety profile was manageable and generally consistent with the known profile. Here we report additional efficacy endpoints. Methods: Adult patients with previously untreated locally recurrent inoperable or metastatic TNBC, for whom immunotherapy was not an option, were randomized 1:1 to Dato-DXd (6 mg/kg IV every 3 weeks) or ICC ([nab]-paclitaxel/capecitabine/eribulin mesylate/carboplatin). Dual primary endpoints were OS and PFS by BICR per RECIST 1.1; secondary endpoints included time to second progression or death (PFS2), time to first subsequent therapy or death (TFST), and time to second subsequent therapy or death (TSST). The planned sample size was approximately 600 randomized patients. A stratified log-rank test was used to analyze PFS2, TFST, and TSST. HRs and 95% CIs were estimated from a stratified Cox proportional hazards model. Results: A total of 644 patients were randomized (Dato-DXd: 323; ICC: 321). At data cutoff (25 Aug 2025), median study follow-up was 27.5 months and 53 (8.4%) patients remained on treatment (Dato-DXd: 45 [14.1%]; ICC: 8 [2.6%]). PFS2 was longer with Dato-DXd vs ICC: median 15.6 vs 11.8 months (HR: 0.61 [95% CI: 0.50‒0.74]). Both TFST and TSST were prolonged in the Dato-DXd vs ICC arm: median TFST was 10.9 vs 5.6 months with Dato-DXd vs ICC (HR: 0.49 [95% CI: 0.41‒0.59]) and median TSST was 16.7 vs 12.6 months (HR: 0.67 [95% CI: 0.55‒0.81]). Conclusions: In TROPION-Breast02, improvements in the secondary endpoints of PFS2, TFST, and TSST were observed for patients receiving Dato-DXd compared with ICC, consistent with the dual primary endpoints of OS and PFS by BICR. Alongside the manageable safety profile for Dato-DXd, these data further support Dato-DXd as the new first-line standard of care in this setting. Clinical trial information: NCT05374512 .

526 Background: The PALLAS trial (NCT02513394) investigated the efficacy of the addition of palbociclib (palbo) to standard adjuvant endocrine therapy (ET) to reduce breast cancer recurrence. Previous analyses of this trial have not shown significant benefit of combination palbo+ET over ET alone. Given prior data showing that extent of neutropenia is associated with response to palbo and other cell cycle-specific therapies, we evaluated whether extent of neutropenia could identify responders to palbo in the adjuvant setting. Methods: PALLAS is a global, open-label, phase III trial that randomized patients (pts) with stage II-III hormone-receptor positive, HER2-negative breast cancer to receive ET for ≥5 years with or without standard-dose palbo for 2 years in 28-day cycles. The primary endpoint is invasive disease-free survival (iDFS). For this exploratory analysis, the palbo population was classified into pts with treatment-emergent high-grade neutropenia (HGN) with maximum grade ≥3 (absolute neutrophil count <1000), or low-grade/no neutropenia (LGN) with maximum grade <2; these groups were compared to each other and to the ET alone group for 5-year iDFS outcomes. Logistic regression examined individual baseline characteristics associated with HGN during the first 3 cycles within the palbo group. Impact of HGN during the first 3, 6, and 12 cycles on iDFS was tested using univariate and multivariable landmark Cox regression. Results: The safety population included 5736 pts, 2840 allocated to palbo+ET, 2896 to ET alone. Prior publications reported no new safety signals, low rates of serious infection, and no grade 5 treatment-related events. The palbo+ET group consisted of 1006 (35.4%) LGN and 1834 (64.6%) HGN. 5-year iDFS results are shown in the table. Pts who received palbo+ET and developed HGN by the end of cycle 6 had significantly improved 5-year iDFS compared to those who received ET alone (p=0.04), which remained statistically significant when adjusting for body mass index (BMI), prior chemotherapy, and race. Multivariable logistic regression showed lower BMI, prior chemotherapy, Asian race, and prior mastectomy were significantly associated with HGN (all p<0.05). Conclusions: In this exploratory analysis of the phase III PALLAS adjuvant trial, addition of palbo to ET appeared to be superior to ET alone in pts who developed HGN in the first 6 cycles of treatment but not in those who had LGN. These findings are consistent with observations in the metastatic setting suggesting that neutropenia could be a useful biomarker for palbo concentration and efficacy. Clinical trial information: NCT02513394 . Maximum grade neutropenia measured at end of cycle: 5-year iDFS Palbo+ET HGN (%) Palbo+ET LGN (%) ET alone (%) Hazard Ratio p-value 3 84.9 84.4 1.06 0.54 84.9 82.9 1.17 0.06 6 85.6 84.9 1.08 0.44 85.6 83.4 1.19 0.04 12 86.3 85.9 1.06 0.57 86.3 85.0 1.12 0.20

e12616 Background: Recent studies have demonstrated that cancer cell metastasis, chemotherapy metabolism, and immune activation and response can be affected by host circadian rhythm. In melanoma and lung cancer, late time-of-day (ToD) immunotherapy administration is associated with worse progression-free and overall survival. The addition of pembrolizumab immunotherapy to neoadjuvant chemotherapy is the standard of care for patients with stage II or III triple negative breast cancer (TNBC) based on the KEYNOTE-522 trial. However, whether immunotherapy ToD administration affects pathologic complete response (pCR) rate in these patients is unknown. Methods: Patients with stage II-III TNBC treated with neoadjuvant chemotherapy plus pembrolizumab per the KN-522 regimen from 7/2021 – 9/2024 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Patients who received fewer than 2 cycles of doxorubicin/cyclophosphamide and/or fewer than 4 doses of neoadjuvant pembrolizumab were excluded. Patient and tumor characteristics, dosing/timing of infusions, and surgical pathology were abstracted from medical records. The primary endpoint was pCR rate, defined as absence of invasive carcinoma in breast and axillary node surgical specimens. Univariable and multivariable logistic regression models were used to assess the association of infusion ToD and patient characteristics with pCR. Results: Among 315 included patients, 190 (60%) were White, 54 (17%) were Black, and 58 (18%) were Asian. Median body mass index (BMI) was 26.3 kg/m 2 . 264 (84%) patients had stage II and 45 (14%) had stage III disease. Median pembrolizumab cumulative dose was 1600mg (IQR 1400-1800mg). Median patient-level pembrolizumab infusion time was 2pm (IQR 1pm-3:30pm). 61% of pembrolizumab infusions were given after 2pm and 34% were given after 4pm. 94% of patients received ³20% of their pembrolizumab infusions after 2pm and 67% received ³20% of their pembrolizumab infusions after 4pm. There were no significant differences in clinical characteristics between patients with early vs. late ToD pembrolizumab infusions, including age, race, ethnicity, BMI, clinical stage, number of chemotherapy or immunotherapy infusions, or pembrolizumab total dose. 177 patients (56%) had pCR. In univariable and multivariable analyses, late ToD pembrolizumab or chemotherapy infusions were not significantly associated with odds of pCR, regardless of whether ToD was measured as patient-level median infusion time or percentage of infusions given before or after time cutoffs. Conclusions: Time of day of pembrolizumab infusion was not significantly associated with pCR in TNBC. This contrasts with studies in other cancer types, highlighting the need for further research into ToD effects in TNBC and other tumor types where immunotherapy is utilized.

Background: Triple-negative breast cancer (TNBC) refers to a heterogenous group of breast cancers that lack expression of ER, PR, and HER2. Despite recent advances with immunotherapy (IO) and antibody-drug conjugates (ADCs), TNBC remains the most aggressive subtype, characterized by a high risk of recurrence and a short overall survival in the metastatic setting. Breast tumors with low levels of ER and PR expression (1-10%) clinically behave like TNBC, and clinical management follows the TNBC treatment (tx) paradigm. We and others have identified a subset of breast tumors which are ER/PR/HER2 negative and express the androgen receptor (AR). Enzalutamide (enza), an AR-antagonist, had demonstrated activity in AR+ metastatic TNBC (Traina et al, JCO 2018). Activation of the glucocorticoid receptor (GR) has been implicated as a mechanism of resistance to AR inhibition in prostate and breast cancers (Kach et al, Sci Transl Med 2015). Advanced TNBC remains an area of high unmet need, particularly in patients who are ineligible for or progress following a checkpoint inhibitor. This randomized study will evaluate the efficacy of enzalutamide or enzalutamide plus the GR antagonist mifepristone (mif) as compared to physician’s choice chemotherapy (TPC). Methods: This is a randomized phase II trial; 201 patients (pts) will be randomized in a 1:1:1 fashion to enza, enza with mif, or TPC (carboplatin, paclitaxel, eribulin, or capecitabine). The primary endpoint (endpt) is progression free survival (PFS), and the trial is designed to test the hypothesis that PFS in the pooled enzalutamide arms is superior to TPC; there is 80% power to detect a hazard ratio (HR) of 0.70, corresponding to increase in PFS from 3.5 months (mos) with TPC to 5.0 mos with enza-based tx. Secondary endpts include comparisons of PFS among 3 arms and evaluation of response rate, clinical benefit rate, duration of response, overall survival, safety/toxicity, and patient-reported outcomes by arm. Exploratory endpts include correlation of tumor and circulating markers (AR-V7 in circulating tumor cells and circulating tumor cell DNA) with tx response. Eligible pts must have: ECOG 0-2, metastatic ER/PR low or negative, HER2 negative breast cancer (BC), measurable or evaluable disease (dz), < 2 prior lines of chemotx, any # prior endocrine txs, no prior anti-AR tx, no prior mif, concurrent CYP17 inhibitors prohibited. Pts with PD-L1+ BC must have received prior IO if not contraindicated. Tumors must have AR >/= 10%, normal organ function, no history of brain mets. As of 7/1/2024, 7 of 201 pts have begun protocol-specified tx. This trial is supported by the TBCRC, BCRF, The TaTa Sisterhood Foundation, Pfizer/Astellas, and Corcept Therapeutics. Citation Format: Rita Nanda, Yuan Chen, Katia Khoury, Hope S. Rugo, Erica L. Mayer, Lisa A. Carey, Michelle Melisko, Angemael Syldor, Chaya Friedman, Jennifer Savoie, Fresia Pareja, Britta Weigelt, Sarat Chandarlapaty, Nicholas Turner, Joshua Lang, Marina Sharifi, Suzanne Conzen, Tiffany Traina. TBCRC 058: A Randomized Phase II Study of Enzalutamide, Enzalutamide with Mifepristone, & Treatment of Physician’s Choice in Patients with Androgen Receptor-Positive Metastatic Triple-Negative or Estrogen Receptor-Low Breast Cancer (NCT06099769) [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 P3-08-17.

We evaluated the feasibility, safety, and efficacy of adjuvant bevacizumab, alone or in combination with chemotherapy, in early-stage breast cancer patients with residual invasive disease after neoadjuvant chemotherapy. Feasibility was demonstrated only for bevacizumab with flat-dosed capecitabine. The 36-month recurrence-free survival (RFS) ranged from 58.0% with bevacizumab monotherapy to 75.0% with bevacizumab plus body surface area-dosed capecitabine. Background: Breast cancer patients with residual disease after neoadjuvant therapy have increased risk of recurrence. Novel therapies to decrease this risk are urgently needed. Methods: Two clinical trials (05-055 and 09-134) offered adjuvant bevacizumab-based therapy to stage I-III breast cancer patients with residual disease after neoadjuvant chemotherapy. Study 05-055 evaluated four treatment regimens: bevacizumab (cohort A); bevacizumab with metronomic cyclophosphamide and methotrexate (CM) (cohort B); and bevacizumab with body surface area-dosed capecitabine (cohorts C); or flat-dosed capecitabine (cohort D). The primary endpoint was feasibility and tolerability. In 09-134, patients were randomized to bevacizumab with or without CM; the primary endpoint was recurrence-free survival (RFS). Study 09-134 closed prematurely for lack of accrual. A pooled survival analysis with participants from 05-055 and 09-134 was conducted. Results: Among 213 total patients (05-055, n = 163; 09-134, n = 50), the most common adverse events (AEs) of any grade were headache (49.3%) and fatigue (57.3%). Grade 3-4 AEs were highest in cohorts C (71.4%) and D (72.5%). The 36-month RFS was 58.0% with bevacizumab monotherapy, 62.3% with bevacizumab plus CM, and 72.7%-75.0% with bevacizumab plus capecitabine (depending on schedule). Treatment with capecitabine was independently associated with improved RFS in triple-negative breast cancer (TNBC) (HR: 0.47; 95% CI, 0.23-0.96). Conclusion: This pooled analysis demonstrates that postneoadjuvant bevacizumab plus capecitabine may be associated with improved RFS, especially in TNBC. Each regimen carries moderate toxicity, and despite these treatments, patients with residual disease after neoadjuvant therapy still experience high rates of recurrence, indicating that new strategies are warranted. Clinical Trial Registration: clinicaltrials.gov, NCT00121134 (DFCI Protocol Number: 05-055); NCT00925652 (DFCI Protocol Number: 09-134).

The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy to reduce breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease. PALLAS was an international, multicenter, randomized, open-label, phase III trial, representing a public–private partnership between Pfizer, the Austrian Breast Cancer Study Group, and the U.S. ALLIANCE Foundation. Patients diagnosed with stage II–III, hormone-receptor-positive, HER2/neu negative breast cancer within 12 months of diagnosis had completed all definitive therapy aside from endocrine therapy (started within 6 months prior to study entry) were eligible. All patients were required to submit a formalin-fixed paraffin-embedded (FFPE) tumor block. Patients were randomly assigned 1:1 to receive standard adjuvant endocrine therapy (of physicians’ choice) for at least 5 years with or without 2 years of palbociclib, administered orally at a starting dose of 125 mg daily, given for 21 days followed by a 7-day break. A total of 5,796 patients with HR + /HER2- early breast cancer (including 1,010 with stage IIA) were enrolled. Median follow-up was 50 months for stage IIA patients and 43.1 months overall. In the stage IIA cohort, 4-year iDFS in the palbociclib arm was 92.9

OBJECTIVE:Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate comprised of a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2, a protein that is broadly expressed in several types of solid tumors. Dato-DXd demonstrated statistically significant improvement in median progression-free survival (mPFS) over docetaxel in patients with previously treated metastatic non-small cell lung cancer (mNSCLC) and over the investigator's choice of chemotherapy in patients with previously treated post-endocrine therapy hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). Dato-DXd also demonstrated a distinct safety profile in both trials. The successful implementation of any new anticancer therapy requires learning how to prevent, monitor, and manage treatment-related adverse events (AE). METHODS:Perspectives were gathered from 4 medical oncologists, 2 nursing professionals, and 1 pharmacist with experience using Dato-DXd in either mNSCLC or mBC across several US practices. RESULTS:Here, we share practical insights and management and treatment of key AEs from Dato-DXd, including oral mucositis/stomatitis, nausea and vomiting, ocular surface events, and interstitial lung disease garnered from the multidisciplinary team of health care professionals experienced in treating patients with Dato-DXd. CONCLUSION:Sharing experiences and institutional approaches from real-world clinical practices and multidisciplinary teams who treat patients with Dato-DXd may help provide a better patient experience and improved outcomes to a broader population of patients.

Abstract Background: Standard of care systemic treatment for early stage triple negative breast cancer (TNBC) consists of neoadjuvant chemoimmunotherapy based upon the results of KEYNOTE 522 (KN-522). The KN522 regimen utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has shown superior OS compared to q3week AC in anthracycline and taxane-based regimens (per CALGB 9741 and EBCTCG analyses). We now present a retrospective study of patients treated with ddAC in a modified KN-522 regimen and report real world feasibility, safety, and efficacy endpoints, including exploration of whether sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab impacts outcome. Methods: Patients with TNBC treated at MSK from August 2021 to September 2022 with a preoperative KN-522 regimen were eligible for inclusion. Clinicopathological and demographic data were obtained from chart review. The primary goal of this study was to describe pathologic complete response (PCR) rate, incidence of treatment-related toxicities resulting in treatment delays, and type of toxicity. Treatment delays for toxicity were defined as a >1 week delay in treatment or discontinuation of a treatment regimen component due to a medical reason. Exploratory analysis was conducted to assess efficacy and toxicity of ddAC before or after CbT as well as rate of GCSF usage with CbT. Baseline characteristics, incidence and type of delays, and treatment outcomes were compared between ddAC first and CbT first using two sample non-parametric tests. Results: 129 TNBC patients met eligibility as defined above. Median age of diagnosis was 50. Clinical stage at diagnosis: Stage I 6%, Stage II 83%, and Stage III 11%. 128 patients received ddAC and 1 patient received AC q3week. Of the 128 patients, 54% received ddAC first while 46% received CbT first. Overall PCR rate of 56%. Treatment-related toxicity leading to chemotherapy delays was 61% and immunotherapy delays was 30%. Most chemotherapy delays were due to cytopenias (79%), with neutropenia (66%) most common. Adrenal insufficiency (4%) and hepatitis (5%) were the most common immune-related toxicities leading to delays. Overall, PCR rate was not affected by chemotherapy delays (No Delay 50% vs. Delay 60%, RR 0.83, 95%CI 0.60-1.15, p=0.25) or immunotherapy delays (No Delay 56% vs. Delay 58%, RR 0.96, 95%CI 0.69-1.33, p=0.81). Exploratory analysis comparing sequencing of ddAC vs CbT first showed incidence of CbT delays was 58% in patients treated with ddAC first and 27% in CbT first. Incidence of ddAC delays was 3% in patients treated with ddAC first and 7% in CbT first. Incidence of delays in both ddAC and CbT was 9% in ddAC first and 10% in CbT first. There was no difference in PCR rate (ddAC 55% vs. CbT 58%, RR 0.96, 95%CI 0.70-1.30, p=0.77) or rate of immunotherapy delays (ddAC 32% vs. CbT 34%, RR 0.93, 95%CI 0.55-1.57, p=0.79) based on sequence of chemotherapy. However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, RR 1.37, 95%CI 1.02-1.84, p=0.03), use of GCSF during CbT (ddAC 55% vs. CbT 34%, RR 1.60, 95%CI 1.06-2.45, p=0.02), and treatment-limiting cytopenias at any time point before surgery (ddAC 59% vs. CbT 31%, RR 1.95, 95%CI 1.26-3.00, p=0.001). Conclusions: These real world data support the feasibility and tolerability of ddAC in a modified KN522 regimen. Exploratory analysis on sequencing of ddAC vs. CbT first in this regimen suggests that efficacy is comparable, yet ddAC first is significantly associated with higher rates of treatment delays and cytopenias. Overall, our experience suggests ddAC is a safe and viable modification to KN-522, and sequencing ddAC after CbT may reduce the risk of treatment induced cytopenias. Citation Format: Nicholas Mai, Sara Myers, Sherry Shen, Stephanie Downs-Canner, Yuan Chen, Tiffany Traina, Nour Abuhadra. Dose-Dense Doxorubicin plus Cyclophosphamide (ddAC) and Impact of Chemotherapy Sequence in a Modified KEYNOTE-522 Regimen for Neoadjuvant Treatment of Triple Negative Breast Cancer: Real World Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-12.

12022 Background: Late alopecia is defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or from initiation of endocrine therapy. It has been reported in up to 25-30% of cancer survivors and is associated with decreased quality of life and reduced dose intensity of cancer therapies. Minoxidil is an aminopyridine potassium channel opener, resulting in vasodilation and premature entry of resting hair follicles into the anagen (growth) phase and increase in hair follicle size. This study aims to assess clinical outcomes and adverse events of oral minoxidil for the treatment of cancer therapy-related late alopecia. Methods: We retrospectively assessed all women with late alopecia treated with oral minoxidil (1.25 mg daily) evaluated at an oncodermatology referral program between 1/2018-5/2021. Outcomes were assessed by standardized photography (4 views) and trichoscopy (HairMetrix, Canfield Scientific, Inc.). Trichoscopy recorded hair density (hair count/cm2) and hair thickness (shaft diameter) at uniform frontal and occipital target areas (12 and 36 cm midline from the glabella, respectively). Adverse events were recorded and graded using CTCAE v5.0. Descriptive statistics were used to summarize the patient demographics and clinical characteristics. Changes in trichoscopy measurements from baseline to follow-up were estimated using paired t-tests. Results: Two hundred and sixteen patients (mean age 57.8±13.7) were included for analysis. Thirty-one (14%) received chemotherapy alone, 65 (30%) endocrine monotherapy, and 120 (56%) chemotherapy followed by endocrine therapy. The majority of patients (n = 170, 79.1%) had a history of breast cancer. Standardized photography assessments (n = 119) after a median of 105 days (IQR = 70) on oral minoxidil revealed clinical improvement in 88 (74%). Trichoscopy assessments (n = 42) after a median of 91 days (IQR = 126) demonstrated increased frontal hair density (124.2 vs 153.2 hairs/cm2, p = 0.008) and occipital hair density (100.3 vs 123.5 hairs/cm2, p = 0.004). There was no statistically significant difference in average frontal or occipital hair thickness (69.3 vs 67.3 μm, p = 0.22, and 70.3 vs 69.9 μm, p = 0.84, respectively). No patients reported discontinuation of oral minoxidil due to adverse effects. Conclusions: Oral minoxidil may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy. This regimen was well tolerated by patients. Prospective, controlled studies are needed to confirm these observations.

Background Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. Methods We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. Findings From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11 center dot 6 months for patients in the standard-of-care group and 12 center dot 1 months for patients in the SBRT group. The median progression-free survival was 3 center dot 2 months (95% CI 2 center dot 0-4 center dot 5) for patients in the standard-of-care group versus 7 center dot 2 months (4 center dot 5-10 center dot 0) for patients in the SBRT group (hazard ratio [HR] 0 center dot 53, 95% CI 0 center dot 35-0 center dot 81; p=0 center dot 0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10 center dot 0 months [7 center dot 2-not reached] vs 2 center dot 2 months [95% CI 2 center dot 0-4 center dot 5]; HR 0 center dot 41, 95% CI 0 center dot 22-0 center dot 75; p=0 center dot 0039), but no difference was found for patients with breast cancer (4 center dot 4 months [2 center dot 5-8 center dot 7] vs 4 center dot 2 months [1 center dot 8-5 center dot 5]; 0 center dot 78, 0 center dot 43-1 center dot 43; p=0 center dot 43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. Interpretation The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. Funding National Cancer Institute. Copyright (c) 2023 Elsevier Ltd. All rights reserved.