Citations

Abstract Rural and low-socioeconomic status women face social determinants of health barriers leading to disproportionately low rates of breast cancer screening and markedly reduced participation in clinical trials. To address this gap, we developed the WeCARE (Women’s Engagement for Cancer Awareness, Resources, and Education) intervention using a community-engaged approach. This paper describes how Community Advisory Board feedback informed the development of Mayo Clinic Health System’s WeCARE intervention components. Their input was systematically analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0) to identify determinants of acceptability, appropriateness, and feasibility and to guide actionable refinements to intervention content and delivery.

Abstract Background The ability of large language models (LLMs) to work collaboratively and screen studies in a systematic review (SR) is under-explored. Hence, we aimed to evaluate the effectiveness of LLMs in automating the process of screening in systematic reviews. Methods This is an observational study which included labeled data (title and abstracts) for five SRs. Originally, two reviewers screened the citations independently for eligibility. A third reviewer cross-checked each citation for quality assurance. GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 were used using zero-shot chain-of-thought prompting. Collaborative approaches included (i): conflict resolution using benefit of the doubt, (ii) majority voting using an independent third LLM and (iii) conflict resolution using an informed third LLM. Performance was assessed using accuracy, precision for exclusion, and recall for inclusion. Work saved over samples (WSS) was computed to estimate the reduction in manual human effort. Results A total of 11300 articles were included in this study. The individual models, GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 exhibited a high precision for exclusion, achieving 99.7%, 99.7%, and 99.2% and high recall for inclusion achieving 95.5%, 96.6% and 85.7%, respectively. However, the collaborative approach utilizing the two best-performing models (GPT-4 and Claude-3S) achieved an average precision of 99.9% and a recall of 98.5% (across all collaborative approaches). Furthermore, the proposed collaborative approach resulted in an average WSS of 63.5%, compared to the average WSS of 45.2% for individual models. Conversational LLM interactions showed a consistent pattern of results. Limitations This study was limited due to reliance on proprietary models, and evaluation on oncology datasets. Conclusion Evidence shows that collaborative LLMs enable efficient, high-performing screening in systematic reviews, supporting continuous evidence updates. Primary funding source NIH (U24CA265879-01-1) and Carolyn-Ann-Kennedy-Bacon Fund.

Abstract Background Central nervous system (CNS) metastases are a major clinical concern in patients with HER2-positive metastatic breast cancer (MBC). The PATINA phase III study showed improved PFS with palbociclib added to maintenance anti-HER2/endocrine therapy (44.3 vs. 29.1 months; hazard ratio 0.75; 95% CI 0.59-0.96; 1-sided P=0.0109). Preclinical and early clinical data suggest palbociclib may have CNS activity. We conducted a pre-specified secondary analysis to evaluate the incidence and timing of CNS progression. Methods CNS progression was defined as the emergence of new intracranial lesions per investigator assessment. Baseline CNS imaging was not mandated but recommended if symptomatic. Competing risks analyses evaluated time from registration to first CNS progression or death (CNS PFS), treating non-CNS progression as a competing event. All randomized patients were included in the primary analysis, regardless of known baseline CNS involvement. Patients with baseline CNS metastases were not censored if progression involved the CNS. A secondary analysis excluded patients with CNS metastases present at baseline. Cumulative incidence functions were estimated and compared using 2-sided Gray’s test. Results Data cutoff for this analysis was on October 15, 2024. 518 participants were enrolled between June 2017 and July 2021, 261 to the palbociclib arm and 257 to the control arm. CNS metastases at baseline were present in 11 patients in the palbociclib arm and 9 patients in the control arm. Among all randomized patients, CNS progression occurred in 35 of 261 (13.4%; 95% CI: 9.5-18.2) in the palbociclib arm and 50 of 257 (19.5%; 95% CI: 14.8-24.8) in the control arm. When excluding patients with CNS metastases at baseline, CNS progression was observed in 32 of 250 (12.8%; 95% CI: 8.9-17.6) in the palbociclib arm and 47 of 248 (19.0%; 95% CI: 14.3-24.4) in the control arm. The median follow-up for patients who were alive and progression-free was 53.5 months. At 36 months, the cumulative incidence of CNS PFS was 13.4% vs. 19.9% for palbociclib versus control (Gray’s test p=0.0386). Importantly, when the analysis was restricted to pts without evidence of CNS disease at baseline (Table 1), —the CNS benefit with palbociclib was maintained (13.0% vs. 19.2% at 36 months, Gray’s test p = 0.0378). Conclusion The addition of palbociclib to anti-HER2 and endocrine therapy was associated with a lower incidence of CNS metastases. Among patients without known baseline CNS involvement, the absolute reduction in CNS progression at 36 months was 6.2% in favor of palbociclib. This benefit was observed at 12 months and sustained over 3 years (Table 1). These findings suggest that palbociclib may help delay or prevent CNS involvement in HR+/HER2+ MBC, warranting confirmation in future studies. Citation Format: O. Metzger, S. Mandrekar, T. Dockter, L. Gianni, E. Ciruelos, A. De Michele, J. Gligorov, E. Lim, S. Loibl, X. Gonzàlez Farré, F. Lynce, J. Lanzillotti, L. Carey, S. Goel, A. Partridge, E. Winer. Central Nervous System Outcomes from the Phase III PATINA Trial (AFT-38) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF4-01.

Abstract Background: While there are abundant data on the surgical management of BC after neoadjuvant chemotherapy (NAC), there is less guidance regarding surgical management of BC after NET, particularly with respect to lymph node (LN) surgery. While pathologic complete response (pCR) is common with NAC, it is a rare event with NET. In this analysis we assess the surgeons’ approach in the context of NET. Methods: The ALTERNATE trial is a phase III study that randomized postmenopausal patients (pts) with clinical stage II/III ER+ HER2- BC to receive neoadjuvant anastrozole (A), fulvestrant (F), or both for 6 mos. before surgery. The primary objective was to determine if neoadjuvant F or A+F increases the rate of pCR or ypT1-2N0/N1mic/Ki67 <2.7% residual disease over A alone. Breast surgery was per standard of care. Sentinel lymph node biopsy (SLNB) with or without axillary lymph node dissection (ALND) was required to determine preoperative endocrine prognostic index PEPI score and residual cancer burden (RCB). Surgeons were required to indicate if the patient would be eligible for breast- conserving surgery (BCS) prior to NET. Patient accrual occurred from 2014-2018. The surgical outcomes are reported for the entire group. Results: Among the 3 treatment arms, 933 patients completed 6 cycles of NET. The clinical T stage at diagnosis was 73.6% T2, 22.6% T3and 3.8% T4. Initial tumor size was assessed by mammogram and ultrasound. Primary tumor histology was ductal in 64.8% and lobular in 25.4%.568 pts (60.9%) were clinically node negative (cN0), 36.2% cN1, 2.6% cN2 with 0.3% cN3. LNs were palpable in 25.2%. 383 had LN needle biopsy pre NET, of which 80.9% were positive. The surgeons’ initial impression of the patient’s eligibility for BCS was 74% while 0.6% were considered inoperable.75.5% of pts had post-NET imaging performed. Of those with tumor size recorded, 52.9% were T1 or not visible. Overall, 69.9% of the 933 patients had BCS. Of those 330 pts without post-NET imaging or who had post-NET imaging without a size noted, 64.8% underwent BCS. For pts undergoing BCS, 80.2% required only one surgery for margin clearance. Of the 690 pts deemed eligible for BCS pre NET, 79% had BCS. Of the 240 pts deemed ineligible for BCS pre-NET, 43.8% had BCS. Of the pre-NET cT2 tumors, 79% had BCS while only 45.5% of T3 tumors and 37.1% of T4 tumors had BCS. On surgical pathology, 474 (50.8%) pts were LN+ compared to pre-NET cN+ 39.1% and needle biopsy-proven 33.2%. For pts with pN0, 93.3% had SLNB alone. 6.7 % of pN0 had ALND alone or SLNB+ALND. For those with pN1-3 , 36.3% had SLN only; 37.3% SLN+ ALND; 26.4% ALND alone. Only 0.8% of the patients had no ALND or SLNB performed. Pts undergoing BCS were more likely to have SLNB alone for a +SLN compared to mastectomy pts (62.9% vs. 37.6%; chi-square p<0.0001). For pts with pre-NET +LN on needle biopsy, only 26.8% underwent SLNB alone, while 37.4% underwent ALND alone. Of the 204 LN-positive pts having SLNB alone, 55.9% had only 1 + LN and 27% had only 2+ LNs. For pN+ pts who underwent SLNB +ALND, 42.1% had 1-2 + LNs. Conclusion: With NET, 69.9% of pts achieved BCS, including 43.8% deemed ineligible pre-NET. Given the low rate of pCR to NET, there should not be the expectation of pCR in +LNs. Based on the procedures performed in pts with +SLNs, it appears that surgeons were applying ACOSOG Z0011 criteria for pts having BCS, but were less likely to omit ALND for +LN in pts having mastectomy. The finding of only 1-2 +LNs in many of the LN+ pts suggests that omission of ALND may be a reasonable approach post-NET. Longer follow-up is required to assess local-regional recurrence. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: A. M. Leitch, T. Dockter, V. suman, A. Weiss, G. W. Unzeitig, J. Guenther, S. Sanati, K. Vij, J. Hoog, A. Caudle, A. Tiersten, M. Mita, W. Razaq, T. J. Hieken, Y. Wang, M. Rimawi, M. J. Ellis, E. Winer, K. K. Hunt, A. H. Partridge, L. A. Carey. Surgical outcomes in the ALTERNATE trial (Alliance A011106) -a randomized phase 3 neoadjuvant endocrine therapy (NET) trial in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF1-02.

Abstract Background: In the treatment of ER+/HER2- metastatic breast cancer (MBC), randomized phase II/III trials testing selective estrogen receptor degraders (SERDs), proteolysis-targeting chimeras (PROTACs), complete estrogen receptor antagonists (CERANs) and selective ER modulators (SERMs) (mostly compared to fulvestrant) have demonstrated modest (1-2 months) improvements in progression-free survival (PFS), mainly limited to patients with ESR1-mutated MBC. In these studies, the median PFS (mPFS) ranges from 3 to 6 months, with shorter mPFS in patients with prior progression on CDK 4/6 inhibitor (CDK 4/6i). Here we report the final results of a randomized phase II study that compared Z-endoxifen (Endx) 80 mg/day with tamoxifen (Tam) 20 mg/day in postmenopausal women with estrogen receptor (ER)- positive/ HER2-negative MBC, and report outcomes according to ESR1, PIK3CA, PTEN and AKT alterations (Alliance A011203; NCT02311933). Methods: Postmenopausal women with unlimited prior endocrine regimens (including CDK 4/6i) and up to two chemotherapy regimens for MBC, with tumor biopsy confirmation of ER+ (>10% nuclear staining) and negative for HER2 amplification/overexpression were eligible. Prior adjuvant Tam was allowed if relapse was > 1 year following Tam completion. Patients randomized to Tam could cross over to Endx at progression. The primary end point was PFS analyzed by the interval censored data analytic approach. ctDNA was analyzed for ESR1 and PIK3CA/PTEN/AKT alterations using Guardant360 CDx 74-gene next-generation sequencing-based assay (Guardant Health). Results: Among 108 women who preregistered, 76 (Endx: 40; Tam: 36) were randomized and eligible. Patients were heavily pretreated; all patients had prior exposure to an aromatase inhibitor (AI), 50% had ≥ 2 AI based regimens in the metastatic setting and 50% in each arm had received fulvestrant. Approximately half on each arm received at least one chemotherapy regimen in the metastatic setting. Prior CDK 4/6i therapy was imbalanced (48% on Endx and 28% on Tam). Endx did not significantly prolong PFS compared to Tam (median PFS [mPFS] 4.3 vs 1.7 months; HR 0.72, p=0.168). Because arms were imbalanced according to prior CDK 4/6i exposure, we performed an unplanned analysis demonstrating that Endx improved PFS relative to Tam in CDK 4/6i-naïve patients (mPFS 8.3 vs 2.1 months; HR 0.39, p=0.0097) but not in patients treated with prior CDK 4/6i (mPFS 3.0 vs 1.5 months). In the subset of patients who consented for ctDNA testing (n=28), the mPFS for those with either an activating alteration in the PIK3CA/PTEN/AKT pathway or with an ESR1 mutation was similar as the overall trial. For the 24 patients who progressed on Tam and crossed-over to Endx, the median PFS was 3.5 months (range 1.5-15.0 months) with a 6-month clinical benefit rate of 33.3% (8/24; 90% CI: 17.8-52.1%). Conclusions: Endx did not meet the prespecified threshold for concluding that it significantly improved PFS relative to Tam in a cohort of heavily pretreated MBC. However, the observations of a > 6-month improvement in mPFS in CDK 4/6i-naïve patients, anti-tumor activity following crossover to Tam, and mPFS estimates similar to other novel endocrine agents in development all support the ongoing development of Endx. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180820 (ECOG-ACRIN) and 5P50CA116201. Clinicaltrials.gov Id: NCT02311933. https://acknowledgments.alliancefound.org. Citation Format: M. P. Goetz, V. Suman, J. Reid, T. Dockter, C. Strand, W. F. Symmans, J. Hawse, A. Storniolo, J. Doroshow, J. M. Collins, H. Streicher, M. M. Ames, A. Tarnower, O. M. Hahn, J. N. Ingle, L. Carey, A. Partridge. Final results from the Randomized Phase II study of Z-Endoxifen and Tamoxifen in Endocrine Refractory, Estrogen Receptor Positive, HER2 negative Metastatic Breast Cancer (Alliance A011203) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-07.

Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.

Objectives To estimate the proportion and correlates of self-reported financial difficulty among patients with multiple myeloma (MM) or chronic lymphocytic leukaemia (CLL). Setting Sixty-six US community and minority oncology practices affiliated with the National Cancer Institute Community Oncology Research Programme (NCORP). Participants A total of 521 patients (=18 years) with MM or CLL consented and 416 responded to a survey (completion rate=79.8%). Respondents had a MM diagnosis (74.0%), an associate degree or higher (53.4%), were White (89.2%), insured (100%) and treated with clinician-administered drugs (68.0%). Study design Observational, theoretical model and protocol-based patient survey administered between May 2019 and June 2020. Primary and secondary outcome measures Financial difficulty was assessed using a single-item measure, the EORTC QLQC30: Has your physical condition or medical treatment caused you financial difficulties in the past year? and using an any-or-none composite measure of 22 items assessing financial difficulty, worries and the use of cost-coping strategies. Multivariable logistic regression models assessed the association of financial difficulty with diagnosis, socioeconomic and treatment characteristics. Results About 16.8% reported experiencing financial difficulty using the single-item measure and 60.3% using the composite measure. Most frequently endorsed items in the composite measure were financial worry about having to pay large medical bills related to cancer and difficulty paying medical bills. Financial difficulty using the single-item measure was associated with having MM vs CLL (adjusted OR (aOR), 0.34; 95% CI, 0.13 to 0.84; p=0.02), having insurance other than Medicare (aOR, 2.53; 95% CI, 1.37 to 4.66; p=0.003), being non-White (aOR, 2.21; 95% CI, 1.04 to 4.72; p=0.04) and having a high school education or below (aOR, 0.36; 95% CI, 0.21 to 0.64; p=0.001). Financial difficulty using the composite measure was associated with having a high school education or below (aOR, 0.62; 95% CI, 0.41 to 0.94; p=0.03). Conclusions US patients with MM and CLL report financial difficulty, especially those with low socio-economic status. Interventions are needed to mitigate patients financial difficulty. Trial registration number NCT03870633 .

Abstract The intracluster correlation coefficient (ICC) measures the correlation of observations within clusters and is a key parameter for power and sample size calculations for cluster randomized trials (CRTs). To facilitate the design of future CRTs within the National Cancer Institute Community Oncology Research Program (NCORP), all studies from the NCORP website were reviewed to identify completed CRTs. ICCs for primary and secondary outcomes (when available) were ascertained from these trials and summarized in this article as a resource for future trial development. Although ICCs are relatively small for many outcome cluster combinations, that is not always the case, so consideration should always be given to the specific outcome of interest, trial design, and type of cluster when estimating an ICC to facilitate trial development.