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Impact of fertility concerns on endocrine therapy.
Ruddy, Kathryn Jean, Kushi, Lawrence H., Liu, Bolun, Laurent, Cecile, Abrahão, Renata , Chao, Chun, Sauder, Candice, Keegan, Theresa, Nichols, Hazel, Ruddy, Kathryn J. , Li, Jia , Kushi, Lawrence H. , Sauder, Candice A. M. , Chubak, Jessica , Hahn, Erin E , Keegan, Theresa H.M.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 631-631

10.1200/jco.2026.44.16_suppl.631 Get It

631 Background: Adolescent and young adult (AYA) women with breast cancer who have not completed their desired childbearing pre-diagnosis may be more likely to decline adjuvant endocrine therapy (ET) and/or to temporarily or permanently stop ET to pursue pregnancy. Fertility counseling and use of fertility preservation strategies (e.g., oocyte/embryo cryopreservation) might impact these decisions. Methods: In the Valuing Opinions and Insights from Cancer Experiences (VOICE) Study, we investigated whether use of fertility preservation strategies were associated with ET initiation and early discontinuation amongst AYAs with fertility concerns. Eligible females were diagnosed with stage 1–3 estrogen-receptor positive breast cancer at age 15-39 during 2013-2022 and responded to a survey in 2023-2024. Those who reported that they had not completed their desired family size or had been unsure about having completed their desired family size at the time of their cancer diagnosis were categorized as having had fertility concerns. ET initiation was defined as 2+ ET prescription fills within 18 months after diagnosis. Among ET initiators, we assessed early discontinuation (defined as lack of ET prescription fill over any 180 day period until 5 years after their first ET fill date). Due to inadequate power, we did not model the relationship between oocyte/embryo cryopreservation and ET initiation. However, we did have power to assess the association between oocyte/embryo cryopreservation and ET discontinuation using multivariable Cox regression to calculate Hazard Ratios (HR) and 95% Confidence Intervals (CI). HRs for discontinuation were adjusted for age at diagnosis, stage, study site, diagnosis year, income, and children before diagnosis (yes/no). Results: Among 518 AYA breast cancer survivors, 56% (N = 290) had fertility concerns at diagnosis. Of these 290, 41% had 1+ child before diagnosis, 90% received fertility counseling, 27% froze eggs or embryos, and 10% had 1+ child after diagnosis. The majority (89%) initiated ET. Among the 32 who did not initiate ET, 7 (22%) reported that fertility concerns impacted that decision. Oocyte/embryo cryopreservation was used by 26% of ET initiators and 34% of ET non-initiators. Among the 258 ET initiators, 89 (35%) discontinued ET early. Compared to those who did not use fertility preservation strategies, patients who froze oocytes/embryos were more likely to discontinue ET (HR 1.89; 95% CI 1.18–3.05). Among those who discontinued ET, 19% had 1+ child after diagnosis (compared to 2% among those who did not discontinue ET). Conclusions: This study confirmed prior studies showing that many AYAs with breast cancer have fertility concerns, and these concerns may impact decisions about ET. In our analysis, those who cryopreserved oocytes/embryos were more likely to discontinue ET early, and a higher proportion who discontinued ET had 1+ live birth after breast cancer.
Long-term safety outcomes of pregnancy among young breast cancer survivors: Results from a prospective, multicenter cohort study.
Zheng, Yue, Niman, Samuel M. , Dibble, Kate, Rosenberg, Shoshana M., Ruddy, Kathryn Jean, Gelber, Shari , Tamimi, Rulla, Peppercorn, Jeffrey , Schapira, Lidia, Come, Steven E. , Warner, Ellen, Lambertini, Matteo, Ginsburg, E, Partridge, Ann H., Sorouri, Kimia , Dibble, Kate E. , Rosenberg, Shoshana M. , Kirkner, Gregory J. , Ruddy, Kathryn J. , Tamimi, Rulla, Schapira, Lidia , Borges, Virginia F. , Warner, Ellen , Lambertini, Matteo , Ginsburg, Elizabeth S. , Partridge, Ann H.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 632-632

10.1200/jco.2026.44.16_suppl.632 Get It

632 Background: Prospective data on the risk of breast cancer (BC) recurrence among young BC survivors who have a subsequent pregnancy are limited. We sought to evaluate the long-term impact of pregnancy and live birth on BC outcomes in the Young Women’s Breast Cancer Study (NCT01468246), a prospective multicenter study of women aged ≤40 years at BC diagnosis. Methods: Women with stage 0-III BC without prior hysterectomy were included. The primary endpoint was breast cancer-free interval (BCFI) between patients with and without a (a) pregnancy and (b) live birth after BC. Secondary endpoints were distant recurrence-free interval (DRFI) and overall survival (OS). A time-varying Cox proportional hazards model was performed by estrogen receptor (ER) status, controlling for age at diagnosis, tumor stage, HER2 status, tumor grade, parity at diagnosis, and germline pathogenic variant status. Results: Among 1,016 BC survivors at a median follow-up of 12 (range, 0.5-18.5) years, 198 reported ≥1 pregnancy and 165 reported ≥1 live birth post-diagnosis. Among survivors who reported a post-diagnosis pregnancy, median age at diagnosis was 32 (range, 17-40) years; most had stage I (35%) or II (40%) BC, with 72% hormone receptor (HR)-positive and 25% HER2+; 42% were nulligravid and 60% were nulliparous at diagnosis. Among BC survivors who did not become pregnant post-diagnosis, median age at diagnosis was 37 (range, 21-40) years; most had stage I (35%) or II (43%) BC, with 75% HR-positive and 28% HER2+; 25% were nulligravid and 29% were nulliparous at diagnosis. Among BC survivors with ER-positive tumors (n = 737), pregnancy after BC was not associated with a difference in BCFI (adjusted hazard ratio [HR] 0.60, 95% CI 0.31-1.16, P = 0.130), DRFI (HR 0.73, 95% CI 0.35-1.55, P = 0.416), or OS (HR 0.58, 95% CI 0.24-1.40, P = 0.227). Similarly, live birth after BC did not impact BCFI (HR 0.83, 95% CI 0.45-1.55, P = 0.560), DRFI (HR 1.04, 95% CI 0.52-2.06, P = 0.923), or OS (HR 0.77, 95% CI 0.34-1.76, P = 0.541). Outcomes among BC survivors with ER-negative tumors (n = 278) were also not affected by post-diagnosis pregnancy (BCFI [HR 1.48, 95% CI 0.70-3.14, P = 0.304], DRFI [HR 1.59, 95% CI 0.68-3.75, P = 0.287], OS [HR 0.99, 95% CI 0.39-2.49, P = 0.975]) or live birth (BCFI [HR 1.02, 95% CI 0.41-2.53, P = 0.974], DRFI [HR 0.80, 95% CI 0.24-2.69, P = 0.722], OS [HR 0.39, 95% CI 0.09-1.69, P = 0.208]). Conclusions: In this multicenter, prospective study with 12 years of median follow-up, pregnancy and live birth after BC did not impact BC events or overall survival, irrespective of ER status. These long-term data from a modern cohort provide reassurance for young BC patients interested in future fertility. Clinical trial information: NCT01468246 .
Patient-reported outcomes from the adjuvant ado-trastuzumab emtansine (T-DM1) for older patients with HER2+ breast cancer (ATOP) trial.
Ruddy, Kathryn Jean, Ginos, Brenda, Heiling, Hillary, Rogak, Lauren , Atanasov, Stafan S., Sinclair, Sarah, Fenton, Mary Anne, Muss, Hyman, Sinclair, Natalie, Hamilton, Erika P., Dang, Chau T., Faggen, Meredith, Lo, S., Mitchell, Sandra A., Winer, Eric P., Dueck, Amylou C., Ruddy, Kathryn J. , Heiling, Hillary , Sedrak, Mina S. , Atanasov, S., Sinclair, Sarah , Mortimer, Joanne , Fenton, Mary Anne , Sinclair, Natalie, Lo, Steve, Mitchell, Sandra A , Winer, Eric P. , Dueck, Amylou C. , Freedman, Rachel A.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 635-635

10.1200/jco.2026.44.16_suppl.635 Get It

635 Background: Prospective data on efficacy, quality of life, and treatment-related toxicities in older adults with breast cancer are limited. The ATOP trial (NCT03587740) evaluated T-DM1 in older adults and demonstrated favorable 5-year invasive disease-free survival. Here, we report patient-reported adverse events (AEs) and health-related quality of life (HRQOL) findings from ATOP. Methods: ATOP was a single-arm, phase II, multicenter study of adjuvant T-DM1 for those aged 60 with stage I-III HER2+ breast cancer. Protocol therapy included postoperative administration of T-DM1 (3.6 mg/kg) every 21 days for one year (17 cycles). PRO-CTCAE (assessing specific symptoms) and EQ-5D (a measure of HRQOL) surveys were administered electronically or on paper at baseline (pre-treatment), on Day 1 of each treatment cycle, and at a single 6–12-month post-treatment time point. Participants who responded to the baseline and at least one follow-up survey were included in the PRO analysis. EQ-5D changes from baseline were assessed using general linear mixed models. Summary statistics were used to assess PRO-CTCAE scores to evaluate which symptoms developed between baseline and 1 subsequent survey(s) and their severity. Results: Among the 111 patients enrolled on ATOP (median age=71, range 60-88 years), 98 responded to the baseline survey and 1 subsequent survey(s). 1435 surveys were returned that included at least one PRO-CTCAE response, and 1661 surveys were returned that included EQ-5D. The Table displays the % of participants who reported PRO-CTCAE symptoms that worsened from baseline to any severity level (scores >0) or to a severe level (scores ≥3). More than 60% of survey respondents reported new or increased dry mouth, fatigue, muscle aches, decreased appetite, nausea, pain, and/or numbness/tingling at some point during or after treatment, but these were usually not severe. EQ-5D scores did not change significantly from baseline at any time point. Conclusions: In this adjuvant trial for patients aged >60, participation rates for PRO data collection were high. Reassuringly, global HRQOL was not impacted by T-DM1, and though frequently reported, the vast majority of patient-reported symptoms were mild. Future analyses of this trial will focus on duration and predictors (clinical and biomarker-based) of severe AEs, agreement between patient-reported and clinician-reported AEs, and whether sharing PRO reports with clinicians impacted clinician-reported AE grades. Clinical trial information: NCT03587740 . Most common new or worsening symptoms reported via PRO-CTCAE in ATOP (n=95). Symptom % with score >0 n (%) with score 3+ Dry mouth 79% 26% Fatigue 71% 29% Muscle aches 69% 20% Decreased appetite 69% 12% Nausea 67% 6% Pain 66% 21% Numbness/tingling 65% 9% Blurry vision 60% 4% Mouth or throat sores 60% 5%
EA1181: Accuracy of pre-surgery MRI to predict pathologic complete response after taxane, trastuzumab, and pertuzumab (THP) in HER2-positive breast cancer.
Tung, NM, Zhao, Fengmin, Partridge, Savannah C., Wright, Jean, Recht, Abram, Weiss, Anna, Tjoe, Judy A., Feldman, Sheldon M. , Smith, Mary Lou , O'Sullivan, Ciara Catherine, Sardesai, Sagar D., Winer, Eric P., Partridge, Ann H., Carey, L, DeMichele, Angela, Tung, Nadine , Zhao, Fengmin , Partridge, Savannah C , Recht, Abram , Weiss, Anna, Tjoe, Judy A., Rocque, Gabrielle B. , O’Sullivan, Ciara C. , Sardesai, Sagar , Badve, Sunil , Winer, Eric P. , Miller, Kathy D. , Partridge, Ann H. , Carey, Lisa A. , Rahbar, Habib , DeMichele, Angela , Wolff, Antonio C.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 603-603

10.1200/jco.2026.44.16_suppl.603 Get It

603 Background: Accurate prediction of pathologic complete response (pCR) after preoperative therapy for HER2-positive (HER2+) breast cancer can help triage patients to immediate surgery vs additional preoperative therapy. Pre-surgery (i.e., after neoadjuvant therapy) imaging studies may help estimate the likelihood of pCR. In EA1181, patients (pts) with stage II-IIIA HER2+ breast cancer received four cycles of preoperative taxane, trastuzumab, and pertuzumab (THP×4). Pre-surgery imaging was required, though the specific imaging modality was not mandated. Here, we report the accuracy of pre-surgery breast MRI to predict pCR (ypT0/Tis, ypN0). Methods: Among 2,141 pts treated with THPx4, 1,378 had pre-surgery breast MRI and were representative of the overall cohort, although T3 tumors were more common (16% vs 9%). MRI reports were available for 1,351 pts; all reports were centrally reviewed and classified as radiologic complete response (rCR; no residual tumor enhancement and normalization of lymph nodes, if applicable) or radiologic residual disease (rRD). Reports with indeterminate radiologic response were independently reviewed by two study radiologists blinded to pathology outcomes. Among pts with rCR who had pathologic residual disease (pRD), we also assessed the extent of residual disease by residual cancer burden (RCB) score. Among pts with rRD who had a pCR, we determined the proportion who only had residual ductal carcinoma in situ (DCIS). Results: See Table. Conclusions: After neoadjuvant therapy, preoperative MRI accurately predicted pCR in 86% of patients with HER2+/ER− disease and may help identify patients who can proceed directly to surgery. MRI is insufficient to predict pCR for pts with HER2+/ER+ disease, as only 55% with complete response on MRI had a pCR at surgery. A pre-surgery MRI that indicated residual disease was accurate in 80% of pts with HER2+/ER+ disease, but in only 45% of pts with HER2+/ER- cancer. Accurately predicting residual disease after THPx4 allows for consideration of additional therapy that may increase the chance of pCR. Combining imaging like MRI with other biomarkers, such as tissue-based markers or circulating tumor DNA, may improve prediction of pCR and facilitate personalization of treatment decisions in HER2+ breast cancer. All pts with pre-surgery MRI (n=1351)pCR rate overall in this cohort = 47% MRI result Pathology pCR pRD rCR 70.6% (341/483) 29.4%(142/483) 78% had RCB1 rRD 34%(295/868) 21% of 295 had DCIS only 66.01% (573/868) ER- (n=589)*Overall pCR rate in ER- subset = 68% MRI result Pathology pCR pRD rCR 86.1% (205/238) 13.9% (33/238) 85% had RCB1 rRD 55.3% (194/351) 19% of 194 had only DCIS 44.7% (157/351) ER+ (n= 762)*Overall pCR rate in ER+ subset = 31% MRI result Pathology pCR pRD rCR 55.5% (136/245) 44.5% (109/245) 76% had RCB1 rRD 19.5% (101/517) 26% of 101 had only DCIS 80.5% (416/517)
A randomized phase II trial of folate receptor alpha peptide vaccine in early-stage triple-negative breast cancer.
Knutson, Keith L., Hillman, DW, Cogen, Davitte , Moreno-Aspitia, Alvaro, Northfelt, Donald W. , Ernst, Brenda, Isakoff, Steven J. , Tolaney, Sara M., Calfa, Carmen, Nanda, Rita, Cole, John T., Fagbemi, Seth, Rowland, Kendrith M., Perez, EA, Chumsri, Saranya, Ruddy, Kathryn Jean, Knutson, Keith L. , Hillman, David W. , Moreno‐Aspitia, Alvaro , Ernst, Brenda , Tolaney, Sara M. , Calfa, Carmen, Nanda, Rita , Mortimer, Joanne , Fagbemi, Seth O., Perez, EA, Norton, Nadine , Chumsri, Saranya , Ruddy, Kathryn J.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 536-536

10.1200/jco.2026.44.16_suppl.536 Get It

536 Background: Folate receptor alpha (FRα) is overexpressed in ~80% of triple-negative breast cancers (TNBC). We previously demonstrated that patients (pts) with breast cancer naturally mount immune responses to FRα. In prior Phase I and II studies, a GM-CSF-adjuvanted FRα peptide vaccine (FRPV) was safe and induced durable FRα-specific T-cell immunity in 83–90% of pts with breast and ovarian cancer. Methods: Eligible pts were women ≥18 years with TNBC (ER/PR ≤10%) with 1+ of the following: stage ≥T1c disease, node-positivity, or residual disease after neoadjuvant chemotherapy. Pts were randomized 2:1 to receive FRPV or placebo (GM-CSF alone) every 28 days for cycles 2-7 and then every six months for 7 booster doses, with cycle 1 consisting of cyclophosphamide 50mg orally twice daily for days 1-7 and 15-21 (in both arms). Randomization was stratified by chemotherapy setting (adjuvant only vs neoadjuvant) and stage (I/II vs III). FRα expression was evaluated by immunohistochemistry. The study was designed to detect (at 30 months after the last pt enrolled) a disease-free survival (DFS) difference of 14% assuming a 3.5-year DFS rate of 70% in the control group and with 78% power. Results: 280 pts were enrolled (median age 52). The majority had stage I or II tumors (n = 219, 78%). There were numerically more node-positive tumors in the vaccine arm, 78 (41%) vs 27 (32%), p = 0.15. Median follow-up was 3.5 years, and 33 (FRPV: 25, placebo: 8) DFS events were observed; 3.5-year DFS rate was 88% with FRPV and 90% with placebo (HR 1.42, 95% CI 0.64–3.15; p = 0.39). Overall survival (OS) also did not differ by arm (HR 2.48, 95% CI 0.55–11.20; p = 0.22). Among node-positive pts (n = 105), DFS did not differ between arms (HR 0.95, 95% CI 0.34–2.66; p = 0.92). However, a numerical DFS event rate improvement (14% for vaccine vs. 26% for placebo) was observed in 61 patients with stage III disease (HR 0.51, 95% CI 0.16–1.68; p = 0.26). DFS did not differ by chemotherapy setting or by receipt of anthracycline, capecitabine, and/or an immune checkpoint inhibitor. FRPV was well tolerated, with predominantly grade 1–2 adverse events (AEs) and no vaccine-related grade ≥4 AEs. FRα expression was available from tumor in 230 pts, with 72% expressing > 0. Overall, DFS was not significantly associated with FRα expression (0 vs > 0; HR 0.55, 95% CI 0.21–1.44; p = 0.21), and no significant differences in DFS by FRα expression were observed between treatment arms. Conclusions: FRPV following oral cyclophosphamide was safe, with no vaccine-related high-grade AEs. While no significant improvement in DFS or OS was observed overall, a numeric trend toward improved DFS was observed in pts with stage III TNBC. This finding is hypothesis-generating and supports further evaluation of FRα-targeted vaccination in higher-risk TNBC. Immune correlative analyses are ongoing to better define vaccine immunogenicity and its relationship to clinical outcomes. Clinical trial information: W81XWH-15-1-0293.
Impact of prior treatment setting on the efficacy of rucaparib vs physician’s choice in BRCA -mutated castration-resistant prostate cancer (mCRPC) in TRITON3.
Sridhar, Srikala S., Fizazi, Karim Olivier, Chowdhury, Simon, Ryan, Charles J. , Alonso-Gordoa, Teresa, Arranz, José Ángel, Birtle, Alison , Byard, Ian, Carrozza, Francesco , Giorgi, Ugo De, Duran, Ignacio, Goeminne, Jean-charles, Goldfischer, Evan R., Despain, Darrin, Craib, Marcia, Lindberg, Henriette , Sridhar, Srikala S , Fizazi, Karim , Bryce, Alan H. , Chowdhury, Simon, Alonso‐Gordoa, Teresa , Giorgi, Ugo De , Durán, Ignacio , Goeminne, Jean‐Charles, Goldfischer, Evan R., Grimm, Marc‐Oliver , Despain, Darrin , Craib, Marcia L.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 5054-5054

10.1200/jco.2026.44.16_suppl.5054 Get It

5054 Background: Rucaparib significantly improved radiographic progression-free survival (rPFS) versus physician’s choice of docetaxel or an androgen-receptor pathway inhibitor (ARPI) (abiraterone or enzalutamide) in men with BRCA mutations who were chemotherapy-naïve in the mCRPC setting and had received one prior ARPI in the phase 3 TRITON3 trial (NCT02975934). This post-hoc analysis evaluated whether the timing of prior ARPI therapy impacted the efficacy of rucaparib. Methods: Patients were randomized 2:1 to rucaparib (600 mg BID) or physician’s choice of docetaxel or ARPI, after progression on 1 prior second-generation ARPI in any setting. The primary endpoint was rPFS. Outcomes were analyzed according to whether patients received the prior ARPI in the metastatic castration sensitive (mCSPC) or castration resistant (mCRPC) setting. Data cutoff was August 25, 2022. Results: Of the 302 BRCA1/2 patients, 68 received prior ARPI in the mCSPC setting (42 rucaparib; 26 physician’s choice) and 234 in the mCRPC setting (159 rucaparib; 75 physician’s choice). Baseline characteristics were generally similar. Prior treatments in the mCSPC and mCRPC groups, respectively, included abiraterone (73.5% vs 53.0%), enzalutamide (29.4% vs 48.3%), and docetaxel (17.6% vs 24.8%). Median rPFS favored rucaparib over physician’s choice in both groups (mCSPC: 13.6 vs 8.2 months; HR 0.60 [95% CI, 0.32–1.15]; mCRPC: 11.2 vs 5.8 months; HR 0.43 [95% CI, 0.30–0.61]). Median OS was similar between treatments in both settings (mCSPC: 23.2 vs 21.7 months; HR 0.81 [95% CI, 0.47–1.41]; mCRPC: 23.2 vs 21.0 months; HR 0.91 [95% CI, 0.66–1.25]). Treatment-related adverse events occurred at comparable rates (89.6% vs 86.1%). Conclusions: Rucaparib demonstrated efficacy in patients with BRCA-mutated mCRPC, regardless of whether prior ARPI was administered in the mCSPC or mCRPC setting. Clinical trial information: NCT02975934 .
First-in-human trial of BH-30643, a novel macrocyclic, non-covalent, mutant-selective OMNI-EGFR inhibitor, in EGFR -mutant ( EGFR m) NSCLC.
Le, Xiuning, Spira, A, Gupta, Divya , Nagasaka, Misako, Riess, Jonathan W., Yang, James Chih Hsin, Rotow, Julia K., Bazhenova, Lyudmila, Li, Molly SC, Izumi, Hiroki, Parikh, K, Hayashi, Hidetoshi, Philipovskiy, Alexander, Kim, Chul, Cui, J. Jean, Zhou, Jihao, Oxnard, Geoff, Zalutskaya, Alena , Horinouchi, Hidehito, Le, Xiuning , Spira, Alexander I. , Nagasaka, Misako , Riess, Jonathan W. , Yang, James Chih‐Hsin , Bazhenova, Lyudmila , Hayashi, Hidetoshi , Philipovskiy, Alexander V. , Johnson, Melissa L. , Cui, J. Jean , Zalutskaya, Alena A. , Horinouchi, Hidehito

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 3014-3014

10.1200/jco.2026.44.16_suppl.3014 Get It

3014 Background: Macrocyclic next-generation tyrosine kinase inhibitors (TKIs) have transformed outcomes in ALK- and ROS1-positive NSCLC; such creatively designed medicines are similarly needed to improve outcomes in EGFR-mutant NSCLC. Using a novel, mutant-selective macrocyclic structure, BH-30643 was designed for super-potency against driver EGFRm, largely sparing wildtype (WT) EGFR, and with unique invulnerability to resistance from C797S with or without T790M. Here we report emerging first-in-human dose-escalation data from the SOLARA trial (NCT06706076). Methods: Phase 1 dose escalation used a BOIN design with backfill at potentially efficacious doses. Expansion cohorts targeted populations of interest. Patients (pts) had advanced NSCLC with EGFR and/or HER2 mutations detected on local testing (tissue or plasma). Measurable disease was required; asymptomatic untreated brain metastases (BM) were permitted. Objectives included safety, PK, and RECIST response rate (ORR). Plasma NGS was performed at baseline and on treatment. Results: As of 01/05/2026, 72 pts enrolled into dose escalation and backfill across 7 dose levels at a total daily dose of 20mg -160mg, median age 62, 44% Asian, 65% with history of BM, median of 3 prior lines of treatment (range 1-12). EGFR mutations included classical (38 pts), exon20ins (14 pts) and other/atypical (18 pts) or HER2 mutations (2 pts). Plasma exposures at doses of 40mg BID and above achieved > 10x coverage over target EC90 and exceeded exposure levels of most contemporary EGFR TKIs. Common TRAE ( > 10%) were WT EGFR-associated, including diarrhea (38%), rash (28%), fatigue (15%), stomatitis (13%), and were predominantly grade 1. Bilirubin elevation was seen in 26 pts (36%) related to off-target UGT1A1 inhibition (Gilbert’s-like). Grade 3 TRAE were seen in 15 pts (18%), most commonly bilirubin (8/15); DLTs included bilirubin increase and mucositis, occurring at doses ≥ 60mg BID. No pneumonitis was observed. Responses were observed across diverse EGFRm subsets, including in CNS. Including expansion pts, 28 pts enrolled with C797S on their most recent informative molecular testing (6 with concurrent MET+ or KRAS+), with 23 still on therapy. Of 17 with on-treatment scans, partial responses (confirmed or ongoing) were seen in 10 (59%); ORR was comparable with (50%) or without (66%) T790M. Of 9 pts with baseline C797S detected in ctDNA (3 with T790M), 7 had > 99% reduction of C797S VAF on treatment. Conclusions: Leveraging a novel macrocyclic scaffold, BH-30643 is the first TKI monotherapy to demonstrate clinical responses against C797S both with or without T790M. High plasma exposures combined with super-potency, CNS activity, and favorable safety offers potential for deep and durable EGFR inhibition. Enrollment into backfill and expansion cohorts is ongoing to better characterize activity in both TKI-naïve and resistant pts. Clinical trial information: NCT06706076 .
Effect of an EHR-facilitated symptom surveillance intervention on rehabilitation utilization in cancer patients.
Barksdale, Touré, Hanif, Subha, Herrin, Jeph, Grzegorczyk, Veronica , Ruddy, Kathryn Jean, Pachman, Deirdre R. , Cheville, Andrea L., Herrin, Jeph , Ruddy, Kathryn J. , Cheville, Andrea L.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 1587-1587

10.1200/jco.2026.44.16_suppl.1587 Get It

1587 Background: Rehabilitation services (physical medicine and rehabilitation [PM&R], physical therapy [PT], occupational therapy [OT], and speech-language pathology [SLP]) improve physical function, symptom burden, and quality of life for cancer survivors, yet utilization remains low due to persistent barriers. The collaborative care model–based Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial improved symptom burden and palliative care utilization. Using post hoc exploratory analyses of population-level trial data, we evaluated whether this EHR-facilitated approach also increased rehabilitation service use. Methods: E2C2 was conducted across Mayo Clinic Midwest medical oncology practices using an unblinded, stepped-wedge, cluster-randomized cohort design. The EHR-embedded intervention targeted SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and fatigue). Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Patients received self-management materials for moderate symptoms (4–6/10) and care manager support for severe symptoms (7–10/10). All outpatient rehabilitation encounters across the Mayo Clinic Enterprise were abstracted. Mixed-effects Poisson models estimated intervention effects on rehabilitation visits during the first 365 days of exposure. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled. Intervention and control conditions included 31,719 and 28,938 patients, respectively, with 10,450 contributing data to both periods. Cross-sectionally, 25% of participants reported moderate and 9% severe physical function impairment. Of 91,220 rehabilitation encounters scheduled, 57,669 (63.3%) were completed. Completed encounters were predominantly PT (68.3%), followed by OT (16.4%), physician visits (9.4%), and SLP (4.2%). The intervention was associated with a more than fourfold increase in completed rehabilitation encounters during the six weeks following index symptom assessment (adjusted mean 2.22 [95% CI, 0.14–4.29] vs 0.54 [0.40–0.68]; incidence rate ratio 4.11 [1.43–11.82]; P =0.009). Scheduled encounters also favored the intervention but did not reach statistical significance. Conclusions: An EHR-embedded symptom surveillance intervention increased short-term rehabilitation service completion, but overall utilization remained low relative to the prevalence of physical function impairment, highlighting the need for system-level strategies to translate symptom identification into sustained rehabilitation engagement.
Unmet rehabilitation needs in cancer survivors: A population-level analysis.
Hanif, Subha, Barksdale, Touré, Cheville, Andrea L., Herrin, Jeph, Ruddy, Kathryn Jean, Pachman, Deirdre R. , Grzegorczyk, Veronica , Cheville, Andrea L., Herrin, Jeph , Ruddy, Kathryn J.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 1584-1584

10.1200/jco.2026.44.16_suppl.1584 Get It

1584 Background: Decades of evidence demonstrate that patients across the cancer continuum may benefit from validated rehabilitation services, yet delivery remains inconsistent. Prior reports of underuse have largely relied on small, single-site cohorts and have lacked population-level estimates of service need, referral, and visit completion, contributing to the assumption that provider reluctance to refer is a primary driver. Using post hoc exploratory analyses of population-level trial data, we evaluated patient- and system-level factors associated with non-use of rehabilitation services. Methods: This secondary analysis used data from the Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial, an unblinded, stepped-wedge, cluster-randomized cohort study comparing an EHR-embedded symptom surveillance and management system with usual care. All patients receiving care in Mayo Clinic Midwest medical oncology practices were enrolled regardless of cancer stage or phase. Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Sociodemographic and clinical characteristics and all outpatient rehabilitation encounters across the Mayo Clinic Enterprise were extracted from the EHR. Rates and types of completed, canceled, and no-show rehabilitation encounters were examined. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled; 34% reported moderate or severe physical function impairment during follow-up. Despite this, only 8,818 patients (17.6%) completed at least one rehabilitation encounter. Of 91,220 encounters scheduled, 57,669 (63.3%) were completed (mean 6.5; median 3 per participant), leaving a substantial proportion canceled or no-showed (n=33,523, 36.7%). Completed encounters were predominantly physical therapy (68.3%), with fewer occupational therapy (16.4%), physician (9.4%), and speech therapy (4.2%) visits. Encounters were concentrated among patients with breast, hematologic, gastrointestinal, and genitourinary cancers. Completion was more likely among patients who were older, female, partnered, retired, and federally insured, whereas cancellations and no-shows were more common among younger, racial or ethnic minority, urban, unpartnered, employed, college-educated, and commercially insured patients (all P <0.001). Virtual visits and encounters in community (vs academic) settings were more likely to be completed (all P <0.001). Conclusions: A substantial gap persists between cancer survivors’ rehabilitation needs and service receipt, varying by cancer type and sociodemographic factors. High cancellation and no-show rates suggest that underuse extends beyond referral and underscore the need for redesigned, more accessible rehabilitation delivery models.
Fertility concerns, counseling, and preservation in AYA females with early-stage breast cancer: Chemotherapy receipt and timing.
Nichols, Hazel, Laurent, Cecile, Keegan, Theresa, Casperson, Mallory, Abrahão, Renata , Chao, Chun, Sauder, Candice, Wernli, Karen J. , Kushi, Lawrence H., Ruddy, Kathryn Jean, Liu, Bolun , Li, Jia , Keegan, Theresa H.M. , Chubak, Jessica , Casperson, Mallory, Green, Laura Elizabeth , Sauder, Candice A. M. , Hahn, Erin E , Kushi, Lawrence H. , Ruddy, Kathryn J.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 1564-1564

10.1200/jco.2026.44.16_suppl.1564 Get It

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6