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Ivonescimab (ivo) with oxaliplatin + fluorouracil (5-FU) + leucovorin calcium (mFOLFOX6) for patients (pts) with unresectable metastatic colorectal cancer (mCRC): A phase 2 study.
3576 Background: Ivonescimab is an investigational tetrameric bispecific antibody targeting both programmed death protein 1 and vascular endothelial growth factor that demonstrated efficacy and a tolerable safety profile in multiple phase 3 studies in pts with non-small cell lung cancer, and is being investigated in other solid tumor types. This multi-part phase 2 study (NCT05382442) evaluated ivo + chemotherapy as first-line treatment of mCRC. Here, we report interim results from the multiregional regimen extension phase of the study, which evaluated ivo 20 or 10 mg/kg + mFOLFOX6. Methods: Adult pts (≥18 years) in China and the US with confirmed mCRC who had an Eastern Cooperative Oncology Group score of 0-1, were not candidates for radical surgical resection or local therapy, and had not received systemic anti-tumor therapy in the recurrent or metastatic stage were enrolled; pts who received prior neoadjuvant or adjuvant therapy were permitted if first recurrence/metastasis occurred ≥12 months (mo) after the last dose. Pts were randomly assigned 1:1 to receive intravenous ivo (20 mg/kg or 10 mg/kg) + mFOLFOX6 once every 2 weeks for up to 8 cycles, followed by maintenance with 5-FU + ivo until disease progression, intolerable toxicity, or withdrawal of consent for up to 2 years. The primary endpoints were objective response rate (ORR; assessed by Response Evaluation Criteria in Solid Tumors v1.1) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included disease control rate (DCR) and progression-free survival (PFS). Results: At the time of data cutoff for this interim analysis (December 31, 2025), 49 pts were enrolled (ivo 20 mg/kg + mFOLFOX6, n = 25; ivo 10 mg/kg + mFOLFOX6, n = 24) with an overall median age of 58 years; 79.6% of pts had left-sided tumors, 53.1% had KRAS or BRAF tumor mutations, and 67.3% had liver metastases. Median follow-up was 7.5 mo (range, 3.5-10.3) and 7.1 mo (range, 1.9-10.3) in the ivo 20 mg/kg + mFOLFOX6 and ivo 10 mg/kg + mFOLFOX6 arms, respectively. ORR was 70.8% in each treatment arm; all were partial responses. DCR was 100% in each treatment arm. Median PFS was not reached. PFS rate at 6 months was 95.2% and 84.8% in the ivo 20 mg/kg + mFOLFOX6 and ivo 10 mg/kg + mFOLFOX6 arms, respectively. Grade ≥3 TEAEs related to ivo occurred in 40.0% and 33.3% of patients in the ivo 20 mg/kg + mFOLFOX6 and ivo 10 mg/kg + mFOLFOX6 arms, respectively, and serious TEAEs related to ivo were reported in 24.0% and 16.7% of pts, respectively. TEAEs led to discontinuation of ivo in 4.0% in the ivo 20 mg/kg + mFOLFOX6 arm and in 0% in the ivo 10 mg/kg + mFOLFOX6 arm. No TEAEs led to death. Conclusions: With 7.3 mo follow-up, ivo + mFOLFOX6 showed encouraging efficacy and a manageable safety profile in pts with untreated mCRC. Clinical trial information: NCT05382442 .
Targeted outreach and fecal immunochemical testing (FIT) completion among vulnerable Rhode Island populations.
e22516 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, with disproportionate incidence and mortality among racial and ethnic minorities and residents of low socioeconomic status. Although FIT is an effective, non-invasive screening option, national screening rates remain suboptimal, including in Rhode Island. From 2023 to 2025, Blue Cross Blue Shield of Rhode Island (BCBSRI) implemented an outreach program targeting “vulnerable” members (identified as members of color by race or ethnicity, low-income, disabled, or dual eligibility status) to promote CRC screening and distribute FITs. Methods: A total of 3,829 BCBSRI members aged ≥40 years were contacted. A cluster analysis was employed to identify naturally occurring groups based on shared demographic characteristics. Multinomial logistic regression examined differences across these groups in the likelihood of completing the FIT and reasons for non-completion. Results: Of all members contacted, 120 (3.1%) completed FITs through the program, 317 (8.3%) had already completed screening, 462 (12%) refused screening, 761 (19.9%) had an out of service number, and 2,169 (56.7%) never responded or were lost to follow up. Four distinct groups were identified by age, language preference, and race. Groups 1 and 4 were composed predominantly of white members (56% and 100%, respectively), whereas race was other/unknown in Groups 2 and 3 (100% and 74%, respectively). Groups 3 and 4 consisted mainly of older (60s), English-preferring members, while Groups 1 and 2 were relatively younger (50s) members who were more likely to prefer a language other than English or Spanish. Group 3 (older, English-preferring, race other/unknown) demonstrated the highest FIT completion ( p = 0.0556). Groups 3 and 4 had significantly higher rates of prior FIT completion, and of those who were due, were more likely to refuse screening (p < 0.0001). Group 4, which was entirely White, also had the highest prevalence of having a primary care provider and low-income status. Lastly, Groups 1 and 2 exhibited significantly higher rates of out-of-service phone numbers (p<0.0001). Conclusions: Although FIT completion through the BCBSRI outreach program was low, the findings underscore key barriers to CRC screening among vulnerable populations. The majority of members were unreachable or lost to follow-up, and non-English-speaking and younger patients demonstrated higher rates of nonresponse, suggesting structural and communication barriers to engagement. Older, English-preferring members were more likely to have already completed FITs, indicating differing needs across demographic groups. These results highlight the importance of developing tailored outreach strategies that address language barriers, communication access, and patient education to reduce CRC screening disparities in Rhode Island.
Comparative analysis of neoadjuvant chemoimmunotherapy (chemoIO) versus PD-(L)1 monotherapy (mono) across PD-L1 expression strata in resectable non–small cell lung cancer (NSCLC): A systematic review and meta-analysis of prospective trials.
e20069 Background: Neoadjuvant chemoIO is a standard treatment for resectable NSCLC, and PD-L1 expression correlates with outcomes. However, cross-trial comparative activity versus PD-(L)1-mono across PD-L1 subgroups remains unclear and may help identify patients for chemotherapy-free approaches, as in the metastatic setting. Methods: MEDLINE and SCOPUS (1/2018 to 8/2025) identified prospective neoadjuvant PD-(L)1 mono or chemoIO trials reporting pCR or MPR (excluding observational reports, CTLA-4 or dual ICB, and RT). Random-effects meta-analyses of arm-level proportions used inverse-variance logit models to estimate pooled pCR/MPR by regimen and PD-L1 status, with meta-regression including regimen, PD-L1, and their interaction. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves for exploratory survival analyses using shared-frailty Cox models. Results: Thirty-four treatment arms comprising 2,640 patients were included. Pooled pCR/MPR increased from 6.4%/16.5% with PD-(L)1-mono to 19.7%/35.2% with chemoIO in PD-L1-negative tumors, and from 13.2%/25.8% to 36.1%/53.7% in PD-L1-positive tumors. In PD-L1 ≥50% disease, pooled MPR was 39.3% with PD-(L)1-mono versus 61.3% with chemoIO. Meta-regression estimated a 16.6% higher pCR with chemoIO (95% CI, 8.9 to 24.3) averaged across PD-L1 strata (Table), with a similar pattern for MPR. Exploratory KM-reconstructed IPD analyses, using a shared-frailty Cox model, suggested an apparent EFS signal favoring PD-(L)1-mono versus chemoIO in PD-L1-positive cohorts (HR 0.43; 95% CI, 0.19 to 0.98), noting cross-trial confounding. Conclusions: ChemoIO was associated with higher pCR/MPR than PD-(L)1-mono across PD-L1 strata. Exploratory EFS findings suggest some patients with PD-L1-positive disease may achieve favorable long-term outcomes with PD-(L)1-mono despite nominally lower pCR/MPR, supporting further prospective biomarker-directed studies to refine perioperative strategies. pCR by treatment regimen and PD-L1 status. Treatment regimen PD-L1 status No. of arms Meta-analysis pooled pCR rate % (95% CI) Meta-regression estimated pCR rate % (95% CI) Absolute difference from reference % (95% CI) P value PD-(L)1-mono PD-L1 negative 7 6.38 (2.66–14.54) 2.63 (-4.60–9.85) Reference — PD-(L)1-mono PD-L1 positive 7 13.20 (7.71–21.70) 16.40 (9.21–23.58) 13.77 (6.48–21.06) 0.0002 ChemoIO PD-L1 negative 13 19.69 (13.12–28.48) 19.24 (13.56–24.91) 16.61 (8.93–24.28) <0.0001 ChemoIO PD-L1 positive 13 36.07(28.83–44.00) 33.01 (27.10–38.91) 30.38 (19.64–41.11) <0.0001
A baicalein and oxaliplatin co-loaded nano-delivery system for dual gasdermin-mediated pyroptosis in pancreatic ductal adenocarcinoma.
e16456 Background: Pancreatic ductal adenocarcinoma (PDAC) features a highly immunosuppressive tumor microenvironment (TME). Inducing pyroptosis is a promising strategy to reverse this “cold” TME, but achieving synergistic activation of dual gasdermin (GSDMD/GSDME) pathways with efficient tumor-targeted delivery remains challenging. Methods: We constructed a nano-delivery system co-loading baicalein and oxaliplatin (B/O@NPs). Its mechanisms and anti-tumor efficacy were evaluated in PDAC cell lines (PANC02, MIAPaCa-2), 3D spheroids, immunocompetent subcutaneous models, and patient-derived xenograft (PDX) models. Techniques included confocal microscopy, flow cytometry, western blot, ELISA, RNA-seq, and immunofluorescence. Results: BONPs demonstrated efficient tumor targeting and penetration in vivo. Mechanistically, baicalein inhibited NF-κB nuclear translocation, leading to mitochondrial dysfunction and reactive oxygen species (ROS) burst, which activated the NLRP3/caspase-1/GSDMD pathway. Concurrently, oxaliplatin triggered caspase-3-mediated cleavage of GSDME. This dual activation resulted in synergistic pyroptosis, confirmed by increased LDH release, IL-1β/IL-18 secretion, and cleavage of GSDMD/GSDME. Pyroptosis induced robust immunogenic cell death (ICD), evidenced by calreticulin exposure, HMGB1 and ATP release. In vitro, BONPs-treated tumor cells promoted dendritic cell (DC) maturation. In vivo, B/O@NPstreatment significantly inhibited tumor growth in both subcutaneous and PDX models. Crucially, it remodeled the TME by increasing infiltration of mature DCs (43.2% vs. PBS), CD8+ T cells (49.2% vs. 1.1% in PBS), and the M1/M2 macrophage ratio (9.51 vs. 0.89 in PBS), while also generating effector memory T cells in the spleen. BONPs treatment mitigated the systemic weight loss associated with free oxaliplatin. Conclusions: The B/O@NPs system effectively co-activates dual gasdermin-mediated pyroptosis, leading to potent ICD and remodeling of the immunosuppressive PDAC TME into an immunologically active state, accompanied by favorable safety profile. This nanoplatform presents a novel combinatorial strategy for PDAC treatment.
Demographic characteristics and inpatient outcomes of early-onset pancreatic cancer in the United States.
e16356 Background: Pancreatic cancer (PC) is a leading cause of cancer-related deaths, with a 5-year relative survival rate of roughly 13%. Significantly, the incidence of PC is increasing among patients younger than 50 years, referred to as early-onset pancreatic cancer (EOPC). However, literature is sparse with regards to the demographic, socioeconomic, and clinical differences between EOPC and non-EOPC populations. We aimed to compare national patient characteristics and inpatient outcomes between these groups. Methods: We conducted a cross-sectional study using the 2016-2019 National Inpatient Sample of adult (age >18 years) hospitalizations with PC. PC and clinical outcomes were identified with ICD-10-CM diagnosis and procedures codes. The Charlson Comorbidity Index (CCI) was used to calculate comorbidities. Descriptive analyses were performed with chi-square tests. Multivariable logistic regression was used to evaluate the association between EOPC and clinical outcomes, adjusting for demographics, CCI, cancer stage, hospital region, and type of admission. Survey weights were applied to generate national estimates. Results: Among 417,830 weighted hospitalizations of patients with pancreatic cancer, 23,225(5.6%) were classified as EOPC. The mean age of EOPC patients was 43.4 years versus 69.6 years in non-EOPC (p < 0.0001). Compared with non-EOPC hospitalizations, EOPC patients were more likely to belong to a racial or ethnic minority population (41.6% vs 28.0%), be in the lowest median household income quartile (30.3% vs 24.9%), reside in a metropolitan region (33.2% vs 29.9%), and present with metastatic disease (57.9% vs 51.8%) (all p < 0.0001). There was no significant difference in sex distribution between the groups (male: 51.7% vs 51.2%, p = 0.488). After adjustment, EOPC was independently associated with increased odds of sepsis (aOR 1.17, 95% CI: 1.05-1.29, p = 0.004), pulmonary embolism (aOR 1.40, 95% CI: 1.30-1.50, p < 0.0001), acute respiratory failure (aOR 1.20, 95% CI: 1.03-1.40, p = 0.02), and pancreatic surgery (aOR 1.16, 95% CI: 1.11-1.22, p < 0.0001). No significant association was found with mortality, deep vein thrombosis, and disseminated intravascular coagulation. Conclusions: With the rising incidence of EOPC, it is increasingly important to characterize this subset of patients. Our data reveals that EOPC patients experience substantial disparities, notably increased minority representation, lower socioeconomic status, and delayed presentation. Moreover, despite younger age, EOPC was independently associated with a disproportionately increased risk of severe inpatient complications. These findings underscore the need for earlier detection and equity focused interventions in this patient population. To extend, further research is warranted to better define the biological, environmental, and health system factors contributing to outcomes in EPOC.
Trends in ivermectin medication records with cancer as the primary diagnosis following public attention: A national EHR analysis.
11121 Background: Ivermectin, an antiparasitic agent not indicated for cancer treatment, has received public attention since early January 2025 due to widespread discussion on social media and other non-clinical forums. Little is known about whether the increased visibility may influence medication use or reporting among patients with cancer in real-world clinical data. Methods: We conducted a retrospective descriptive analysis using the EPIC COSMOS, a large, multi-institutional U.S. electronic health record network. We identified all ivermectin medication records from quarter (Q)1 2024 to Q3 2025, including prescribed/administered and patient-reported medications linked to clinical encounters. Our primary outcome was the quarterly trend in the percentage of ivermectin records where cancer was listed as the primary diagnosis for the encounter. Secondary measures included other diagnosis associated with the encounter (e.g., parasitic) and patient demographics. Results: We identified 96,525 ivermectin medication records, increasing from 11,854 in Q1 2024 to 15,223 in Q3 2025. The proportion of records with cancer as the primary diagnosis increased modestly during 2024 (from 2.3% to 3.1%; average quarterly increase=0.2 percentage points [ppts]), followed by a larger increase in Q1 2025 (from 3.1% to 4.2%, adjusted increase=1.0 ppts, relative increase=32%, p<.001), which stabilized in Q2 and declined slightly in Q3 2025. The surge from Q4 2024 to Q1 2025 was larger for patient-reported ivermectin (from 156 to 231 records, 48% increase) than prescribed/administered medications (292 to 347 records, 19% increase). In contrast, the proportion of ivermectin records associated with strongyloidiasis, onchocerciasis, or scabies ranged from 18.5%–19.5% in 2024 and declined to 17.1% in Q1 2025, while records associated with other infectious conditions remained stable (~49%). Among records with cancer as the primary diagnosis (n=3,157), mean patient age was 62 years, with 46% female, 76% White, 8% Black, and 10% Hispanic; the proportion prescribed to White patients increased from 71% in Q4 2024 to 81% in Q1 2025. Physician specialty distribution associated with prescribed/administered ivermectin was 35% oncologists, 20% primary care, 22% dermatologists, 4.2% advanced practice providers, and 19% other specialties. Conclusions: Although ivermectin use in cancer care remained uncommon overall, real-world data show a rapid, largely patient-driven increase during Q1 2025. This rise is distinct from the stable or declining proportions of records linked to approved parasitic indications. These findings suggest that social trends may shape medication use, highlighting the importance of careful medication reconciliation and patient counseling in oncology settings to address non-evidence-based use.
Survival outcomes following salvage surgery for recurrent and residual head and neck squamous cell carcinoma after chemoradiotherapy.
e18066 Background: Recurrent or residual head and neck squamous cell carcinoma (HNSCC) after chemoradiotherapy (CRT) is associated with poor prognosis with the median overall survival (OS) seldom exceeding 12 months. Salvage surgery remains the principal curative option; however, long-term outcome data from the Indian context are limited. This study assesses survival outcomes and prognostic determinants following salvage surgery after CRT failure. Methods: We performed a retrospective analytical study of 129 HNSCC patients who underwent salvage surgery after definitive or adjuvant CRT from 2010 to 2015. Patients with distant metastases or second primary tumors were excluded. Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS). Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards modeling to validate the Perioperative Prognostic Score (PPS). Results: The cohort was 88.4% male, with 95.3% presenting with Stage III/IV disease. Median follow-up was 78.4 months. Median OS was 50.4 months (5-year OS: 42.3%) and median DFS was 32.5 months (5-year DFS: 29.2%). Multivariate analysis identified female sex as an independent protective factor for OS (p=0.023) and DFS (p=0.011). The pre-operative score was a strong predictor; a Level 3 score conferred a 7.8-fold higher mortality risk (p=0.023) and a 10.4-fold increased recurrence risk (p=0.005). Carcinoma of Unknown Primary (CUP) significantly predicted improved survival (median OS: 115.98 months; 80% 5-year OS). Stage IV disease correlated with reduced DFS (p=0.035), whereas age, ECOG performance status, prior treatment intent, and reconstruction type were not significant survival predictors. Conclusions: Salvage surgery offers meaningful long-term survival in CRT-failed HNSCC, with a median OS of 50.4 months. Sex and pre-operative scoring emerged as independent outcome determinants, while traditional clinical staging showed limited prognostic discrimination. These findings indicate a marked “fit-patient” selection bias among salvage candidates, suggesting conventional models lose predictive value in physiologically robust cohorts. Therefore, risk stratification should shift toward detailed biological and functional markers to optimize patient selection.
Tyrosine kinase inhibitors in Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL): A systematic review and meta-analysis.
e18522 Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a rare, life threatening form of leukemia with unique challenges in diagnosis and treatment, and is historically associated with a poor prognosis. The introduction of tyrosine kinase inhibitor (TKI) agents has significantly altered paradigms; however, the relative efficacy between imatinib and standard chemotherapy or newer-generation TKI agents remains uncertain. In this quantitative synthesis, imatinib will be compared to both standard chemotherapy regimen, and newer generation TKIs such as dasatinib and ponatinib. Methods: Databases including PubMed and Cochrane Central were searched for potentially relevant studies, featuring a comparison of either imatinib versus standard non-TKI cytotoxic chemotherapy, or imatinib versus other TKI agents, including new-generation drugs like dasatinib and ponatinib. The included studies must report at least one of: (i) overall survival (OS), (ii) event-free survival (EFS), and (iii) adverse drug reactions. The meta-analysis was conducted via RevMan 5.4 with hazard ratio (HR) and 95% confidence interval (CI) computed. The inverse-variance method with the random-effects model were utilized. A p-value of < 0.05 was declared statistically significant. Results: A total of 9 studies were included in the pooled analysis. Imatinib was marginally inferior to newer TKI agents in terms of overall survival (HR: 1.85; 95% CI: 0.99-3.44; P = 0.05), whereas it was superior compared to non-TKI standard chemotherapy (HR: 0.34; 95% CI: 0.18-0.65; P = 0.001). Imatinib was non-inferior to newer TKI agents in terms of EFS (P = 0.57), whereas it was superior compared to non-TKI standard chemotherapy (HR: 0.35; 95% CI: 0.19-0.64; P = 0.0007). Both comparisons had a comparable incidence of adverse drug reactions, with no statistically significant differences observed. Conclusions: In patients with Ph+ ALL, TKI-based therapy significantly improves survival outcomes in comparison to non-TKI standard cytotoxic chemotherapy. While newer-generation TKIs may offer marginal OS advantage in comparison to imatinib, non-inferior EFS and adverse event rate continue to support its role as an effective treatment strategy. Further large-scale trials, particularly featuring comparisons between first-generation versus new-generation TKI agents, are necessary in order to arrive at a valid conclusion. Number of Studies Hazard Ratio (95% CI) P-value I 2 , % (P-value) Overall Survival Imatinib vs. TKI 2 1.85 (0.99 to 3.44) 0.05 0 (0.43) Imatinib vs. Standard 4 0.34 (0.18 to 0.65) 0.001 25 (0.26) Event-Free Survival Imatinib vs. TKI 3 1.22 (0.61 to 2.46) 0.57 75 (0.02) Imatinib vs. Standard 4 0.35 (0.19 to 0.64) 0.0007 36 (0.20) Adverse Drug Reactions Imatinib vs. TKI 3 1.01 (0.92 to 1.10) 0.89 0 (0.69) Imatinib vs. Standard 4 0.81 (0.60 to 1.10) 0.18 72 (0.01)
Second-line cetuximab plus immune checkpoint inhibitor (ICI) versus cetuximab plus carboplatin and paclitaxel following ICI-containing regimen in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
6046 Background: ICI-containing regimens are the standard first-line therapies for R/M HNSCC. However, the optimal therapeutic regimen after progression on ICI-containing therapies remains uncertain. This study compares outcomes among patients (pts) who received either second-line cetuximab plus ICI (CICI) or cetuximab plus weekly carboplatin and paclitaxel (CPT). Methods: We performed a retrospective analysis of R/M HNSCC pts treated at our institution between 2018 and 2025 who received cetuximab combination therapy after progressing on first-line ICI alone or ICI with chemotherapy. Pts with ECOG 0-2 were included. All pts received cetuximab 400 mg/m 2 followed by 250 mg/m 2 weekly as tolerated, concurrently with either pembrolizumab (200 mg every 3 weeks) or chemotherapy (carboplatin AUC 1.5 and paclitaxel 45 mg/m 2 weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate (DCR; SD+PR+CR), objective response rate (ORR; CR+PR), and rate of treatment modification. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using log-rank tests and Cox proportional hazards models. Fisher’s exact test was used to compare binary outcomes. Results were deemed significant when p<0.05. Subgroup analyses were considered exploratory. Results: Out of 100 pts included, 31 received CICI, and 69 received CPT. Median age at the start of cetuximab was 65 years (range 34-93), 79% were male, 95% were Caucasian, and 38% had HPV-related disease. Primary tumor sites included oropharynx (47%), oral cavity (26%), and larynx (19%). 9% had CPS 0, 30% had CPS 1-19, and 43% had CPS ≥ 20. For first-line treatment, 41% had received an ICI alone, and 59% had received an ICI with chemotherapy. Median follow-up was 7.6 months (range 3.8-13.4) with CICI and 38.8 months (range 4.3-71.5) with CPT. DCR was 77.4% with CICI and 60.6% with CPT (p=0.12). ORR was 51.6% versus 34.8%, respectively (p=0.13). Median PFS was 7.6 months (95% CI 4.1-NR) with CICI and 2.7 months (95% CI 2.0-4.4) with CPT (HR 0.48, 95% CI 0.29-0.82, p<0.01). Median OS was 11.3 months (95% CI 9.1-NA) with CICI and 9.4 months (95% CI 8.2-10.5) with CPT (HR 0.78, p=0.10). Subgroup analyses showed favorable PFS with CICI in select groups: age ≤ 65 (p=0.037), male sex (p=0.009), ECOG 0-1 (p=0.024), and prior ICI plus chemotherapy (p<0.001). No clear differences were found within subgroups with CPS 1-19 or CPS ≥ 20. There was no difference in the rates of treatment modification (p=1.00). Conclusions: In this retrospective cohort of R/M HNSCC pts, CICI was associated with a longer PFS than CPT. This effect remained significant in pts who previously received first-line ICI plus chemotherapy. A longer follow-up is planned to evaluate for differences in OS.
Machine learning to identify racial and socioeconomic disparities in the onset and tumor distribution of second primary malignancies in multiple myeloma.
7551 Background: As survival in Multiple Myeloma (MM) improved with novel therapies, the burden of second primary malignancies (SPM) has emerged as a significant competing risk. While racial disparities in MM outcomes are established, it remains unclear whether the the timing and type of SPM differ by race or socioeconomic status. Methods: We analyzed 7,513 MM survivors from the SEER Research database (2000–2022) who developed a confirmed, invasive SPM (excluding non-melanoma skin cancers). To account for the shorter follow-up duration in the modern era, latency drivers were assessed using Fine-Gray competing risk models which adjust for censoring. Racial and socioeconomic differences were quantified using logistic regression adjusted for age, sex, and median household income. Random Survival Forests were used to identify predictors of SPM latency with variable importance ( VIMP) indicating the contributor for each factor. Results: The mean time-to-SPM decreased from 5.18 years (2000–2010) to 2.61 years (2011–2022) ( p < 0.001 ). Black patients developed SPMs earlier than White patients (Average Direct Effect: -0.33 years, p < 0.001 ) and at a younger mean age for secondary Prostate cancer (68.5 vs. 71.6 years, p < 0.001 ). In Random Survival Forest modeling, biological age (VIMP=0.15) was the primary predictor of latency, followed by Stem Cell Transplant and Radiation utilization (VIMP=0.03). Multivariable linear regression indicated that patients with low household income (<$60k) developed SPMs 0.34 years faster than wealthier peers ( p = 0.009 ). Black patients had significantly lower odds of therapy-related hematologic malignancies (OR 0.62, 95% CI 0.49–0.77; p < 0.001 ) but higher odds of solid tumors (OR 1.62, 95% CI 1.30–2.04; p < 0.001 ). This solid tumor disparity persisted after adjusting for age and income ( p=0.27 ) and was driven by Prostate (OR 1.79, 95% CI 1.54–2.09) and Breast cancer (OR 1.31, 95% CI 1.06–1.62). Post-SPM mortality hazard was higher in Black patients compared to White patients (HR 1.15, p < 0.001 ). Conclusions: Our findings showed racial and socioeconomic factors impact both the timing and type of SPM in MM survivors. Black and low-income patients develop SPM earlier and are more likely to develop solid tumors, especially prostate and breast. These findings suggests need for surveillance strategies and earlier focused screening for high risk populations to address disparities in MM survivorship.
Histopathological distinction between ICI-induced psoriasis vulgaris and psoriasiform dermatitis in patients with immune-related cutaneous adverse events (irDAEs): A multicenter prospective observational study.
e24191 Background: Immune checkpoint inhibitors (ICI) significantly improve survival in cancer patients but are frequently associated with dermatologic immune-related adverse events (irDAEs) that exhibit clinical heterogeneity and may mimic psoriasis. The histopathological distinctions between ICI-induced psoriasis vulgaris and psoriasiform irDAEs remain insufficiently characterized despite their critical importance for accurate diagnosis and treatment decisions. Study Design: Multicenter prospective study including patients who developed irDAEs during ICI therapy and underwent clinical evaluation with or without skin biopsy. Retrospective data collection included demographics, oncologic characteristics, ICI regimens, cutaneous manifestations, CTCAE severity grading, and available histopathological findings, with histologic analysis focused on psoriasiform cases. Methods: The study included 50 patients who developed immune-related cutaneous adverse events during ICI therapy (mean age 69 years; 56% male). The most common underlying malignancies were skin and soft tissue cancers (38%), genitourinary cancers (28%), and lung/bronchial cancers (20%). Results: Isolated pruritus without visible rash was observed in 20 patients (40%). The remaining 30 patients (60%) developed irDAEs of varying severity: Grade 1 in 19 patients (38%), most commonly maculopapular rash (26%), and Grade 2–3 in 11 patients (22%), including psoriasis vulgaris (8%), psoriasiform eruptions (6%), lichenoid eruptions (6%), and bullous pemphigoid (2%). Histopathological evaluation was performed in 7 patients with Grade 2–3 psoriasis vulgaris (n = 4) or psoriasiform eruptions (n = 3). Psoriasiform eruptions showed irregular acanthosis with prominent parakeratosis, preserved granular layer, and mild dermal vascular changes with moderate perivascular lymphocytic infiltrates, whereas psoriasis vulgaris demonstrated regular acanthosis, diffuse parakeratosis, complete loss of the granular layer, and pronounced papillary dermal vascular dilatation with prominent perivascular inflammation. Conclusions: Routine histopathological assessment of the skin is essential for the accurate confirmation of irDAEs. Morphological findings enable the differentiation of these events from other dermatoses and provide a rationale for selecting supportive treatment without unjustified modification of antitumor therapy.
ChatGPT-based conversational AI tool for training oncologists in patient communication: A real-world implementation study.
e13675 Background: Oncologists frequently experience difficulties communicating with patients, particularly when delivering bad news and discussing prognosis. Effective communication training helps physicians conduct these conversations more efficiently and with greater confidence. We developed an artificial intelligence-powered chatbot to support oncologists in patient communication. Methods: We created a chatbot based on the large language model ChatGPT 4.1 integrated into Telegram messenger (@MedcomAI_bot). The bot contains contextual information on established models and protocols of medical communication, including the Calgary-Cambridge consultation guide, the SPIKES protocol for delivering bad news, the CONES protocol for communicating medical errors, and the NURSE acronym for demonstrating empathy. The chatbot also incorporates assessment checklists to evaluate consultations according to these frameworks and evidence-based research in medical communication.The bot operates in three modes: (1) assisting physicians in planning conversations with patients, (2) providing feedback on completed patient interactions, and (3) assessing conversations based on provided transcripts. Results: Between October 2025 and December 2025, 301 physicians utilized the @MedcomAI_bot chatbot, generating 417 distinct dialogues. Of these interactions, 105 (25.2%) received positive user ratings, 306 (73.4%) were neutral, and 6 (1.4%) received negative ratings. The tool demonstrated high engagement, with an average of 1.39 dialogues per physician. Preliminary analysis suggests particular utility in preparing for difficult conversations and obtaining real-time feedback on communication performance. Conclusions: AI-powered conversational tools show promise as scalable, accessible educational resources for training oncologists in medical communication and patient counseling. Further prospective studies are needed to assess impact on communication competency and patient satisfaction outcomes.
Real-world overall survival outcomes of belzutifan treatment in advanced renal cell carcinoma.
4561 Background: Belzutifan, a hypoxia-inducible factor–2α inhibitor, is an emerging therapy for advanced renal cell carcinoma (RCC) that demonstrated significant benefit over everolimus in the LITESPARK-005 trial. We aimed to validate these findings in a real-world setting and identify clinical prognostic factors within a large, multi-institutional cohort. Methods: We conducted a retrospective cohort study, using Epic Cosmos, of adults with RCC who initiated Belzutifan on or after the FDA Approval date (December 14, 2023) to Dec 20, 2025, ensuring at least one month of follow-up prior to the query date. Overall survival (OS) was measured from the treatment start date to death, with censoring at the last clinical encounter. Survival was estimated using Kaplan–Meier methods. Associations between baseline clinical and laboratory variables and OS were evaluated using univariable Cox proportional hazards models with false discovery rate (FDR) correction. Results: A total of 2,844 patients were included; the median age was 66 years, 72% were male, and 51.2% had documented tobacco use. The OS probabilities were 80.9%, 68.1%, 58.3%, and 53.2% at 6, 12, 18, and 24 months, respectively, and comparable to the LITESPARK-005 trial. Among clinical variables, tobacco use was associated with worse survival (HR 1.24 [95% CI 1.08–1.44], FDR = 0.014), whereas female sex (HR 0.78 [0.66–0.92], FDR = 0.014) and higher BMI (HR 0.96 [0.95–0.98], FDR <0.001) were associated with improved outcomes. Markers of nutritional and hematologic reserve were strongly protective, including higher Albumin (HR 0.46 [0.41–0.52], FDR <0.001), Total Protein (HR 0.77 [0.70–0.89], FDR <0.001), Hemoglobin (HR 0.90 [0.87–0.93], FDR <0.001), RBC (HR 0.69 [0.62–0.75], FDR <0.001), and MPV (HR 0.90 [0.84–0.96], FDR = 0.002). Inflammatory and immune markers demonstrated divergent effects: higher Lymphocytes (HR 0.53 [0.46–0.61], FDR <0.001) and Lymphocyte-to-Monocyte Ratio (HR 0.75 [0.71–0.80], FDR <0.001) predicted favorable outcomes. Conversely, worse survival was associated with elevated RDW (HR 1.14 [1.11–1.17], FDR <0.001), Monocytes (HR 1.71 [1.34–2.20], FDR <0.001), Basophil-to-Lymphocyte Ratio (HR 2.39 [1.20–4.77], FDR = 0.019) and Neutrophils (HR 1.06 [1.04–1.07], FDR <0.001),.Higher Corrected Calcium (HR 1.43 [1.30–1.57], FDR <0.001) and Total Bilirubin (HR 1.13 [1.04–1.22], FDR = 0.005) were associated with inferior outcomes. Conclusions: In the largest real-world cohort to date, overall survival after belzutifan initiation mirrored LITESPARK-005, supporting its effectiveness in routine practice. Baseline nutritional, hematologic, and immune markers were associated with improved survival, while systemic inflammation and metabolic dysfunction predicted worse outcomes, highlighting the prognostic value of routine clinical variables.
Oral selective estrogen receptor degraders in HR+/HER2- advanced breast cancer and impact of ESR1 mutation status: A systematic review and meta-analysis.
1081 Background: Oral selective estrogen receptor degraders (SERDs) are a promising therapeutic class for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Several randomized controlled trials (RCTs) have evaluated oral SERDs, but results have varied across agents and populations. Methods: We searched MEDLINE, EMBASE, CENTRAL, and conference proceedings until December 31 st 2025 and identified RCTs comparing oral SERDs with standard endocrine therapy in adults with HR+/HER2- advanced breast cancer. Two reviewers independently screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2. Random effects meta-analysis was performed using generic inverse variance for hazard ratios for progression-free survival (PFS). Odds ratios for safety outcomes were pooled using Mantel-Haenszel (fixed effect). Results: A total of 9 trials comprising 4,258 participants were included. Overall, oral SERDs demonstrated a statistically significant improvement in PFS compared with standard endocrine therapy (HR 0.76, 95% CI 0.60 to 0.97; p=0.03). In the estrogen receptor 1 gene mutated (ESR1m) subgroup (7 trials, n=1,273), oral SERDs showed a more pronounced PFS benefit (HR 0.53, 95% CI 0.39 to 0.70; I²=53.4%; p=0.002). In contrast, patients with ESR1 wild-type tumors (6 trials, n=1,212) derived no significant benefit (HR 0.95, 95% CI 0.81 to 1.12; I²=0%). The interaction between ESR1m and treatment was statistically significant (p<0.001). Grade ≥3 adverse events were similar between groups (RR 1.09, 95% CI 0.87 to 1.38). Treatment discontinuation due to adverse events was significantly higher with oral SERDs (RR 1.65, 95% CI 1.02 to 2.65). Conclusions: Oral SERDs lead to a statistically significant improvement in PFS over standard endocrine treatments albeit with the effect seemingly limited to patients with ESR1m. These results support the use of biomarkers to determine which patients are most likely to receive clinical benefits from oral SERD therapy and underscore the importance of ESR1 testing in order to tailor treatment optimally. ESR1 mutation status subgroup analysis. Subgroup Trials Participants HR 95% CI P-value ESR1 Mutant 7 1,273 0.53 0.39 – 0.70 0.0015 ESR1 Wild-Type 6 1,212 0.95 0.81 – 1.12 0.4684
Impact of para-aortic lymphadenectomy on prognosis and quality of life in preoperative IB2-IIA2 cervical cancer: A multi-center cohort study.
5528 Background: The indication of para-aortic lymphadenectomy (PALD) in preoperative IB2-IIA2 (FIGO 2018) cervical cancer remains unclear. We aimed to access the impact of PALD on the prognosis and life quality in preoperative IB2-IIA2 cervical cancer patients. Methods: This cohort study, a target trial emulation, was conducted at the Obstetrics and Gynecology Hospital of Fudan University, including cervical cancer patients with a preoperative stage of IB2-IIA2 from 2019 to 2023 (clinical trial ChiCTR2400092255). Propensity score matching at a 1:1 ratio (PALD versus non-PALD) was applied to balance baseline characteristics. Primary outcomes were progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). Secondary outcomes included perioperative complications and adverse events (AEs). Kaplan-Meier and subgroup analyses were conducted, and Cox proportional hazard models were established. External validation was performed at another three tertiary hospitals in China. Results: Of the 2609 patients included, 683 (26.2%) underwent PALD during radical surgery. Propensity score matching yielded a cohort of 1250 patients with balanced covariates. Patients who underwent PALD demonstrated similar PFS (hazard ratio 1.27; 95% CI, 0.89-1.80; P=0.188), OS (hazard ratio 1.17; 95% CI, 0.71-1.93; P=0.544), and CSS (hazard ratio 1.20; 95% CI, 0.70-2.06; P=0.512) as those who did not. Additionally, no significant differences were detected in survival associated with receiving PALD among subgroups defined by lymph node status based on preoperative imaging, the para-aortic lymph node (PALN) metastasis prediction model, and other postoperative pathological risk factors. External validation drew consistent conclusions regarding the effect of PALD on survival. Moreover, the PALD group compared with non-PALD group showed more intraoperative hemorrhage (P=0.005), longer operation time (P=0.004), and a higher tendency for chylous fistula (P=0.077). Conclusions: PALD, compared with non-PALD, was not associated with survival benefits for IB2-IIA2 cervical cancer patients yet was associated with increased surgical complications.
Impact of surgical timing on outcomes in patients with borderline-resectable and locally advanced pancreatic cancer undergoing neoadjuvant therapy.
e16460 Background: Neoadjuvant therapy (NAT) followed by resection is standard for borderline-resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and increasingly used in select locally-advanced (LA) cases with adequate tumor response. However, the clinical implications of the interval between NAT completion and surgery are not well characterized, and surgical timing varies widely in practice. We evaluated the association between surgical timing, pathological response, and survival outcomes. Methods: This retrospective study included patients (pts) with BR- and LA-PDAC who underwent NAT followed by resection at a single center. Clinicopathologic and outcome data were extracted from electronic health records. The interval from NAT completion to surgery (interval) was measured in weeks (wks); pathologic response was graded 0–3 using College of American Pathologists (CAP) tumor regression grade (TRG), and associations were evaluated using multivariable logistic regression. Recurrence-free survival (RFS) and overall survival (OS) were calculated from surgery to recurrence/death and death, respectively, and analyzed using Kaplan-Meier and Cox methods. Results: We identified 304 pts with PDAC (71% BR, 29% LA) treated between Feb 2012 and Jun 2022. Median age was 67 years (range: 31–85); 48% were female. NAT consisted of chemotherapy (CT) plus chemoradiotherapy (CRT) in 63% and CT alone in 37% (68% FOLFIRINOX, 26% gemcitabine–nab-paclitaxel), followed by resection (94% pancreaticoduodenectomy, 6% distal pancreatectomy). Median NAT-to-surgery interval was 6.4 wks (1.9–35.9). CAP TRG distribution was: 0 (4%), 1 (9%), 2 (59%), and 3 (28%). At a median follow-up of 65.3 months (mo), 73% developed recurrence and 70% died. Median RFS and OS were 15.2 (95%CI: 11.7–18.7) and 34.4 (95%CI: 28.5–39.4) mo, respectively. Improved TRG, negative margins, absence of lymphovascular space invasion (LVSI), and perineural invasion (PNI) were associated with superior RFS and OS (all p < 0.01) on univariate analysis. On multivariable analysis, longer interval increased the odds of favorable TRG in pts receiving CRT (OR 1.094 per week, 95%CI 1.028–1.164; p = 0.004) but not in those receiving CT alone (OR 1.023, 95%CI 0.896–1.166; p = 0.606). While interval was not independently associated with survival in the overall cohort, pts achieving excellent path response (TRG 0-1, 13% of CRT pts) had significantly longer intervals (10.7 vs 7.5 wks, p = 0.017), improved mRFS (38.4 vs 11.7 mo, p = 0.003), and mOS (NR vs 27.5 mo, p < 0.001). Conclusions: Longer intervals between NAT and surgery in BR- and LA-PDAC were associated with improved path response in pts receiving CRT. Path response correlated with survival outcomes. This potentially reflects a time-dependent maturation of treatment effect and warrants further prospective studies to define the optimal timing of surgery.
Durvalumab plus chemotherapy prior to chemoradiotherapy and followed by durvalumab as consolidation for patients with limited-stage small cell lung cancer (CONCUR study).
TPS8139 Background: The ADRIATIC study demonstrated that durvalumab consolidation therapy following concurrent chemoradiotherapy (CRT) significantly improved both progression free survival (PFS) and overall survival (OS) in patients with inoperable limited-stage small-cell lung cancer (LS-SCLC), establishing the standard of care for this population. Building on emerging immune checkpoint inhibitor (ICI) strategies (pre-CRT induction, post-CRT consolidation or concurrent ICI-CRT), CONCUR study innovatively introduces durvalumab plus chemotherapy as induction to synergize early immune priming with cytotoxic effects, aiming to enhance responses during subsequent CRT while preserving safety, with potential to reshape the treatment landscape for LS-SCLC. Methods: Approximately 100 eligible patients (aged ≥ 18 years) with histologically or cytologically confirmed LS-SCLC, ECOG 0-1, at least one measurable lesion (RECIST 1.1), having received no prior thoracic radiotherapy or chemotherapy will be enrolled in this multi-center, phase II study. Patients will receive durvalumab (1500mg day[D] 1) combined with cisplatin (75 mg/m² D1 or 25 mg/m² D1-3) or carboplatin (AUC 5-6 D1 or AUC 2.5-3 D1 and D8) and etoposide (100 mg/m² D1-3) every 3 weeks for 2 cycles as induction therapy, followed by concurrent or sequential CRT. Thoracic radiotherapy will be delivered as 60 ± 6 Gy (1.8-2 Gy/day) or 45 ± 1.5 Gy (1.5Gy twice daily), with optional prophylactic cranial irradiation per clinical indication and local clinical practice. Patients showing at least stable disease after the definitive CRT will continue durvalumab (1500 mg every 4 weeks) until disease progression, unacceptable toxicities, or for up to 24 months (whichever occurs first). The primary endpoint is PFS by investigator per RECIST 1.1. Secondary endpoints include OS, objective response rate, duration of response, and safety. The primary analysis on PFS will be performed at approximately 60% data maturity. Assuming the median PFS is 16 months (defined from first dose of treatment), with an enrollment period of 12 months and drop-out rate of 7%, 100 patients and 60% PFS maturity will provide a precision of ± 4.8 months with 95% CI (11.6m, 21.1m) estimated by Kaplan-Meier method using Brookmeyer and Crowley method. Enrollment is ongoing. Clinical trial information: NCT07055581 .
Automated detection of tertiary lymphoid structures (TLS) on whole-slide pathology images using an improved YOLO-v12 model and validation of a TLS structural prognostic index (TLS-SPI) across multi-cancer TCGA cohorts.
e13670 Background: Tertiary lymphoid structures (TLS) are important biomarkers reflecting the tumor immune microenvironment and are closely associated with patient prognosis. However, current TLS structural assessment often relies on discrete morphologic grading (e.g., maturity-based classification), which fails to capture the continuous spectrum and complexity of TLS architecture. Therefore, a more systematic quantitative framework is needed to characterize TLS structure along a continuum. In this study, we developed a deep learning model for automated TLS detection on routine H&E whole-slide images (WSIs) and constructed a TLS Structural Prognostic Index (TLS-SPI) for precise risk stratification of overall survival (OS). Methods: This study included WSI data from 2,170 patients in the TCGA pan-cancer cohort, covering STAD, COAD, LUAD, LUSC, and BRCA (TNBC subtype). All WSIs were randomly split into training, validation, and test sets at a 7:2:1 ratio, and then tiled into 512×512 patches at 5× magnification for model training and validation. We trained an automated TLS detection model based on an improved YOLO-v12 architecture, and evaluated performance using TLS-level recall, precision, and F1 score. Furthermore, we constructed TLS-SPI using patient-level quantitative TLS features extracted from automated detection. Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess the association between TLS-SPI and OS, and its prognostic stratification ability was validated in the STAD, LUSC, and COAD cohorts. Results: The improved YOLO-v12 model demonstrated strong robustness for automated TLS detection across multiple cancer types, achieving an overall performance of recall = 0.844, precision = 0.902, and F1 = 0.872. The TLS Structural Prognostic Index (TLS-SPI) derived from this model effectively stratified patients into high- and low-risk groups in the TCGA-STAD, TCGA-LUSC, and COAD cohorts. Multivariable analyses further confirmed TLS-SPI as an independent prognostic factor for overall survival (OS) in these cancer types (LUSC cohort: HR = 0.63, 95% CI 0.47–0.84, p < 0.05), highlighting its significant clinical predictive potential. Conclusions: We established a scalable TLS auto-detection framework applicable across multiple TCGA cancer cohorts and proposed a TLS Structural Prognostic Index (TLS-SPI) that predicts OS and stratifies risk in the STAD, LUSC, and COAD cohorts. This approach provides an extensible path toward standardized TLS quantification from routine H&E slides and supports translational prognostic applications.
POLARIS: Polymetastatic lesion ablative radiotherapy with immunotherapy study.
TPS2683 Background: Patients with polymetastatic disease, most commonly defined as >5 metastatic lesions, often have limited treatment options and poor overall prognosis 1,2 . The emergence of immunotherapy (IO) has slowed disease progression in some patients; however, its efficacy is limited by tumor heterogeneity and patient-specific factors, including baseline health status 3 . Emerging data suggest a synergistic effect when combining IO with radiotherapy (RT), a strategy that has led to FDA-approved treatment approaches in non-small cell lung cancer (NSCLC) 4-6 . As multimodal cancer therapies evolve, robust methods to assess treatment response are increasingly important. Circulating tumor DNA (ctDNA) is a minimally invasive biomarker that has been shown to correlate with clinical response to therapy 7,8 . However, the kinetics and clinical significance of ctDNA in patients receiving combined IO and ablative RT remain poorly characterized. Methods: POLARIS is a pilot phase II, double-arm clinical trial evaluating the addition of ablative radiotherapy in patients with polymetastatic disease receiving immunotherapy. Twenty-eight patients with polymetastatic disease, defined as having at least 3 and no more than 10 metastatic lesions, and receiving immunotherapy alone for at least 30 days prior to registration will be enrolled at the University of Illinois Hospital & Health Sciences System (UIH). Patients will be stratified into two cohorts based on their response to immunotherapy after ≥3 months: Cohort A includes patients with investigator-assessed stable disease or partial response, while Cohort B includes patients with oligoprogression, defined as 1–5 sites of progressive disease within 3 months of registration. Both cohorts will receive ablative RT targeting up to 10 metastatic lesions in combination with ongoing immunotherapy. The primary endpoint is the proportion of patients achieving a molecular response, defined as a >50% reduction in ctDNA levels, at 8 weeks following ablative RT. Secondary endpoints include overall survival and progression-free survival at 6 and 12 months, objective response rate, and treatment-related adverse events (TRAEs). This trial is the first to prospectively evaluate ablative radiotherapy as an adjunct to immunotherapy while integrating ctDNA as a biomarker of treatment response in polymetastatic disease. Clinical trial information: NCT07269080 .
Oxybutynin for vasomotor symptoms across cancer-related and menopause-associated settings: A systematic review and meta-analysis of randomised control trials and observational studies.
10627 Background: Vasomotor symptoms, including hot flashes, are a frequent and debilitating adverse effect among postmenopausal women and patients receiving cancer-directed hormonal therapies, particularly endocrine therapy in breast cancer and androgen deprivation therapy in prostate cancer. Hormone-based therapies are often contraindicated in cancer populations, underscoring the need for effective non-hormonal treatment strategies. Oxybutynin, an anticholinergic agent approved for overactive bladder, has emerged as a potential non-hormonal therapy for vasomotor symptoms; however, the magnitude of benefit and tolerability across randomized studies in diverse clinical populations has not been comprehensively quantified. Methods: A systematic search of PubMed, Embase, Cochrane CENTRAL, and clinical trial registries was performed to identify randomized controlled trials evaluating oxybutynin for vasomotor symptoms in postmenopausal women and cancer populations, including patients receiving endocrine therapy and androgen deprivation therapy. Outcomes included change in hot flash composite score (frequency × severity), change in hot flash frequency, and discontinuation due to adverse effects. Results: 5 studies were identified, including four randomized controlled trials and one observational cohort (409 randomized participants). Oxybutynin was associated with a significant improvement in hot flash composite score compared with control (mean difference 8.81, 95% confidence interval 6.51–11.10; p < 0.00001; I² = 54%). Subgroup analyses demonstrated greater improvement with higher doses (5 mg twice daily) compared with lower doses (2.5 mg twice daily), although both dose ranges were superior to control. Hot flash frequency was significantly reduced with oxybutynin (mean difference 3.88 episodes per day, 95% confidence interval 2.96–4.80; p < 0.00001; I² = 42%), with larger reductions observed with higher-dose regimens. Treatment discontinuation due to adverse effects was more frequent with oxybutynin (odds ratio 2.90, 95% confidence interval 1.19–7.10; p = 0.02; I² = 0%), consistent with a dose-related increase in anticholinergic adverse effects, most commonly dry mouth. Conclusions: Across studies in women and men with cancer-related and menopause-associated vasomotor symptoms, oxybutynin was associated with clinically meaningful reductions in symptom frequency and severity, with evidence of a dose-response relationship and a trade-off with increased anticholinergic adverse effects. These findings inform the role of oxybutynin as a non-hormonal therapeutic option in populations in whom hormonal therapies are limited or contraindicated.