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The hidden struggle? Mental health burden among oncology physicians globally.
9012 Background: Oncology physicians face demanding clinical workloads, high emotional labor, and frequent exposure to patient loss, contributing to elevated psychological distress. While burnout has been extensively described, anxiety and depression remain under-recognized and stigmatized within the oncology workforce. Methods: A cross-sectional, anonymous, online survey distributed internationally (October–December 2025) assessed indicators aligned to PHQ-9 and GAD-7 constructs, mental-health history, medication use, practice characteristics, and workplace context. Descriptive statistics summarized prevalence; χ²/Fisher’s exact tests compared subgroups; and logistic regression explored independent risk factors for anxiety/depression. Results: Among 209 oncology physicians who completed all mental health-related survey items (Table 1), 28.2% reported anxiety and/or depression. Female physicians had a higher prevalence than male physicians (35.4% vs 22.2%, P = 0.037). Anxiety/depression was higher among Hispanic/Latino vs non-Hispanic White physicians (45.5% vs 29.8%, P = 0.015) and among non-U.S. vs U.S.-based physicians (33.3% vs 25.7%, P = 0.025), though these differences attenuated in adjusted models. Medication use was strongly associated with anxiety/depression. Prevalence of anxiety/depression was rare among physicians who had never considered medication (0.9%), but common among those with past (72.7%) or current (92.9%) medication use (P < 0.001). Conclusions: Nearly one in three oncology physicians reported anxiety and/or depression, consistent with national estimates for physicians generally. Female physicians demonstrated a significantly higher burden and retained an independent risk after adjustment. These findings underscore the need for confidential and accessible mental health care within oncology professional environments and highlight the importance of addressing structural and occupational contributors to psychological distress. If oncology is to remain a sustainable profession, mental health must be treated as a core component of workforce development rather than an individual responsibility. Physicians’ characteristics by anxiety/depression. Variable AllN (%) No Anxiety/ DepressionN (%) Yes Anxiety/ DepressionN (%) P value† Total 209 (100.0) 150 (71.8) 59 (28.2) Sex Female 99 (47.4) 64 (64.6) 35 (35.4) 0.037 Male 108 (51.7) 84 (77.8) 24 (22.2) Race / Ethnicity Non-Hispanic White 84 (40.2) 59 (70.2) 25 (29.8) 0.015 Hispanic/Latino 33 (15.8) 18 (54.5) 15 (45.5) Black 11 (5.3) 11 (100.0) —
A randomized, double-blind, placebo-controlled trial of antiviral prophylaxis and oral <i>Herpesviridae</i> dynamics during radiotherapy for head and neck cancer.
TPS12163 Background: Oral mucositis (OM) is a frequent and debilitating toxicity of radiotherapy (RT) for head and neck cancer (HNC), often leading to pain, nutritional compromise, and treatment interruptions. Reactivation of viruses from the Herpesviridae family has been proposed as a potential contributor to the pathogenesis and severity of OM, but prospective, controlled data remain limited. Antiviral prophylaxis is not standard of care in this setting, and its role in preventing viral reactivation and modulating OM severity during RT has not been systematically evaluated. This randomized trial investigates the association between oral Herpesviridae detection, antiviral prophylaxis, and OM development in patients undergoing RT for HNC. Methods: This is a prospective, randomized, double-blind, placebo-controlled phase II trial conducted across four oncology centers in Brazil. Adult patients (≥18 years) with HNC undergoing intensity-modulated radiotherapy (IMRT), with or without concurrent systemic therapy, are randomized 1:1 to receive antiviral prophylaxis or placebo. Randomization is stratified by age (< 60 vs ≥60 years) and anatomic tumor site (oral cavity/salivary glands; oropharynx/pharynx; nasopharynx/paranasal sinuses). The investigational intervention consists of oral antiviral prophylaxis administered once weekly throughout the course of RT; the control arm receives a matching placebo. Comprehensive dental evaluation and oral care optimization are performed prior to RT initiation in all patients. Serial oral mucosal and saliva samples are collected weekly during RT and after treatment completion. Quantitative real-time PCR is used to detect and quantify viruses from the Herpesviridae family, including HSV-1, HSV-2, VZV, EBV, CMV, HHV-6A/B, HHV-7, and HHV-8. Clinical assessments include OM incidence, severity graded by CTCAE criteria, pain intensity, and timing of OM onset and resolution. Correlative analyses will explore temporal associations between viral detection, viral load, antiviral prophylaxis, and OM outcomes. The planned sample size is 84 patients (42 per arm), providing adequate power to detect differences in viral manifestation and OM-related outcomes. Clinical trial information: NCT07363031 .
Pilot study of whole-exome sequencing and single-nucleus RNA sequencing to identify actionable alterations in cancer.
e15078 Background: DNA sequencing employing comprehensive genomic profiling (CGP) or whole-exome sequencing (WES) is widely used to identify targetable mutations and genomic instability phenotypes that guide treatment decisions in cancer. However, these approaches fail to characterize critical features such as cellular composition, tumor and immune cell states, and cell type-specific expression of therapeutic targets. Single-cell transcriptomic approaches have been extensively used in research to address these limitations, but have not yet been translated into clinical practice. Methods: We undertook a pilot study of 13 tumor samples from four cancer types (colorectal, lung, ovarian, pancreatic) using an integrated WES and single-nucleus RNA sequencing (snRNA-seq) approach. Nuclei were extracted from frozen tissue using One Biosciences' protocol optimized to preserve nuclei integrity. A single nuclei suspension was used to prepare both WES and snRNA-seq libraries. WES libraries were sequenced to a median depth of 330X for tumor DNA and 74X for constitutional DNA, while snRNA-seq generated ~600 million reads per sample. Following quality control, molecular features relevant for treatment decisions were extracted and integrated across both modalities. Results: WES identified 11,412 somatic mutations (median 374 per sample). Actionable mutations were detected in 2 patients, including KRAS G12C (targetable with adagrasib or sotorasib in lung cancer) and BRAF V600E (targetable with encorafenib plus cetuximab in colorectal cancer). Two colorectal samples also exhibited mismatch repair deficiency signatures, associated with immunotherapy response. Overall, WES revealed clinically relevant therapeutic opportunities in 3 of 13 patients. SnRNA-seq generated high-quality transcriptomic profiles from 52,302 individual cells (median 4,002 cells per sample; median 1,829 genes per cell), enabling quantitative characterization of lymphoid, myeloid and vascular populations. Analysis of target gene expression for immune checkpoint inhibitors (ICI), antibody–drug conjugates (ADC), and bispecific antibodies (BsAb) suggested additional opportunities in 5 of 13 patients. Integrating WES and snRNA-seq identified potential treatment strategies in 7 of 13 patients. Conclusions: This study demonstrates the feasibility of combining WES with snRNA-seq from a single frozen tumor biopsy. The two modalities provide complementary, clinically actionable insights, identifying opportunities in 3 of 13 patients with WES alone and 7 of 13 patients with the integrated approach. WES primarily guided small-molecule therapy selection based on mutations and DNA repair defects, whereas snRNA-seq facilitated prioritization of biologics, including ICI, ADC, and BsAb. Future efforts will focus on developing an integrated clinical report to support therapeutic decision-making.
Time-dependent patterns of immune-related adverse events by obesity status following immune checkpoint inhibitor therapy: A real-world cohort analysis.
11191 Background: Immune checkpoint inhibitors (ICIs) substantially improve cancer outcomes but are frequently complicated by immune-related adverse events (irAEs). Obesity alters immune regulation and has been paradoxically associated with enhanced ICI efficacy; however, its influence on the timing and persistence of irAEs remains poorly defined. Prior studies have largely evaluated irAEs as binary outcomes, potentially obscuring time-dependent risk patterns. Methods: We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Adults with solid tumors initiating nivolumab, pembrolizumab, ipilimumab, or durvalumab were identified. Patients with pre-existing autoimmune disease, hematologic malignancy, organ transplantation, or prior irAEs were excluded. Patients were stratified by baseline body mass index (BMI ≥30 kg/m² vs 20–24.9 kg/m²). irAEs were identified using diagnosis-based groupings mapped to organ-specific toxicity categories. Survival analyses were performed using landmarked Cox proportional hazards models evaluating early (1–90 days), delayed (91–365 days), and late (366–1825 days) irAE risk. Adjusted hazard ratios (AHR) were calculated after adjustment for age, sex, cancer type, immunotherapy agent, smoking status, diabetes, chronic kidney disease, chronic pulmonary disease, liver disease, and cardiovascular comorbidity. Results: Among 29,564 eligible patients (obese: 13,958; normal BMI: 15,606), obesity was not associated with overall irAE risk across 5 years of follow-up (AHR 0.98, p=0.19). In landmark analyses, obesity was associated with lower early irAE risk (AHR 0.94, p=0.003), no significant difference during the delayed period, and a persistent increase in late irAE risk (AHR 1.11, p=0.003).Time-stratified associations were most pronounced for gastrointestinal, renal, endocrine, and dermatologic irAEs, while pulmonary and neurologic irAEs were not significantly increased after multivariable adjustment. Conclusions: Obesity demonstrated a time-dependent association with immune-related toxicity following ICI therapy, characterized by attenuated early risk and persistent late risk emerging beyond one year. These findings highlight the importance of time-stratified analytic approaches and suggest that absence of early irAEs may not confer long-term safety in obese patients receiving ICIs. Outcome Time Window Adjusted HR (95% CI) p value Any incident irAE 1–90 d 0.94 (0.90–0.98) 0.003† Any incident irAE 366–1825 d 1.11 (1.04–1.19) 0.003† GI irAE 1–1825 d 0.82 (0.77–0.87) <0.001† GI irAE 1–90 d 0.76 (0.68–0.86) <0.001† GI irAE 91–365 d 0.82 (0.74–0.90) <0.001† GI irAE 366–1825 d 0.84 (0.75–0.93) 0.001† Renal irAE 366–1825 d 1.14 (1.01–1.29) 0.031† Endocrine irAE 91–365 d 1.04 (0.99–1.09) 0.089 Endocrine irAE 366–1825 d 1.05 (1.00–1.11) 0.069 †p<0.05.
Addressing housing instability as a quality-of-care determinant in cancer: A meta-analysis across national and Veterans Affairs cohorts.
11045 Background: Housing instability is an under-recognized determinant of cancer outcomes that directly affects screening adherence, treatment delivery, and survival. Over 650,000 Americans experience homelessness nightly, yet its impact on oncologic quality-of-care metrics remains poorly quantified. We conducted a meta-analysis to evaluate disparities in cancer screening, treatment, and survival among persons experiencing homelessness (PEH) versus housed individuals, and to assess whether housing status functions as a system-level quality indicator. Methods: Real-world evidence from the Veterans Health Administration (VHA), National Inpatient Sample (NIS), and community cohorts (2011–2024) was pooled using random-effects DerSimonian–Laird models. Eligible studies reported odds ratios (ORs) or hazard ratios (HRs) comparing PEH with housed counterparts. Heterogeneity was summarized using I² statistics, and all analyses were performed in Stata. Results: Six cohorts contributed sixteen effect estimates encompassing >200,000 cancer cases. PEH were less likely to be up to date for colorectal cancer screening (pooled OR 0.56, 95% CI 0.23–1.31; I² = 93.9%). Homelessness was associated with markedly lower odds of surgery or other invasive procedures (pooled OR 0.42, 95% CI 0.26–0.66; I² = 98.4%) and substantially higher odds of discharge against medical advice (pooled OR 5.37, 95% CI 3.39–8.50; I² = 92.9%). In gastrointestinal cancer admissions, PEH also had longer hospital stays and higher costs. Within VHA datasets, homelessness independently predicted higher all-cause mortality after lung (HR 1.09–1.29) and colorectal cancer (HR 1.18–1.22). Veterans who gained housing after diagnosis achieved survival comparable to continuously housed peers (HR ≈ 1.0). Conclusions: Across diverse U.S. datasets, homelessness is consistently associated with lower screening uptake, reduced treatment receipt, and higher mortality—outcomes that represent measurable quality-of-care failures. Stable housing acts as a protective, modifiable factor influencing survival independent of access or insurance. Incorporating housing status screening into oncology intake workflows can close equity gaps, improve safety, and advance value-based cancer care. Housing stability should be recognized as a core quality metric in oncology. Cohorts included in the meta-analysis of homelessness and cancer outcomes. Study Cancer Type(s) Main Outcomes Effect (95% CI) Asgary 2014 Colorectal Screening OR 0.35 (0.23–0.53) VA Cohort 2011–21 CRC, Breast Screening / Colonoscopy aIRR 0.84 (0.83–0.84); 0.88 (0.84–0.92) Shah 2024 All cancers Procedure / Therapy / AMA AOR 0.53; 0.73; 4.29 Mevawalla 2019 GI Surgery / AMA OR 0.33; AOR 6.86 VA Mortality 2011–20 Lung Mortality HR 1.21 (0.93–1.57) Health Affairs 2024 Lung, CRC, Breast Mortality by housing HR 1.09–1.29 (lung); 1.22 (CRC)
Clinicopathologic and genomic landscape of pancreatic acinar cell carcinoma: A single-center experience.
e16484 Background: Pancreatic acinar cell carcinoma (PACC) is an ultra-rare (~1%) pancreatic malignancy. Management is often extrapolated from pancreatic ductal adenocarcinoma (PDAC) despite distinct molecular drivers. We characterize the clinicopathologic and genomic features of PACC at our center to identify precision oncology targets. Methods: A retrospective review of histologically confirmed PACC at a tertiary academic center was performed. Clinical, radiographic, pathologic, treatment, and outcome data were extracted. Standard of care next-generation sequencing (NGS) results were reviewed, with focus on potentially actionable alterations. Results: Seven patients were identified (median age 64, range 46–70; 57% male). Symptoms included abdominal pain and weight loss; notably, jaundice was absent. Pathologic evaluation demonstrated variable lymph node involvement, lymphovascular and perineural invasion, and occasional mixed acinar neuroendocrine differentiation. NGS was performed in a subset of patients and actionable alterations included 9p21.3 co-deletion (CDKN2A/B and MTAP loss), IZKF1 loss, SEC24D-BRAF fusion, and BAP1 mutation (Table 1). All were KRAS wild-type. Surgical resection was performed in three patients, and FOLFIRINOX chemotherapy was commonly used. Treatment responses varied. A swimmer plot analysis revealed that 2/7 patients had prolonged progression-free survival ( > 90months and > 200months), while the remaining patients had follow-up < 5 years. At the time of data reporting, four patients were alive without disease recurrence and under ongoing surveillance. Conclusions: Our cohort confirms PACC is molecularly distinct from PDAC, characterized by absence of KRAS mutation and high prevalence of targetable alterations. The identification of MTAP loss and BRAF alteration suggests that PACC patients should be prioritized for specific precision medicine trials (e.g., PRMT5 or MAPK inhibitors) rather than traditional PDAC regimens. Early NGS is mandatory to optimize precision treatment in this rare cancer. Patient Age Sex Presenting Symptoms Tumor Location Resection performed NGS Findings MSI Status TMB Potential Target 1 46 F Abdominal pain, nausea, bloating, fatigue Head Yes Not tested Not tested Not tested N/A 2 68 F Pruritis, abdominal pain, appetite loss, constipation/diarrhea Head Yes TP53 mutation; KRAS wild type; CDKN2A/B loss; MTAP loss; SEC24D-BRAF fusion MSS Intermediate BRAF/MEK/PRMT5 inhibitors 3 67 M Abdominal pain Head Attempted (aborted) Not tested Not tested Not tested N/A 4 70 M Flank pain and hematuria Head No Not tested Not tested Not tested N/A 5 86 F Asymptomatic (incidental lab finding) Head No BAP1 mutation MSS 6.6 EZH2 inhibitors 6 55 M Abdominal pain Tail No CDKN2 A/B loss; IKZF1 loss; MTAP loss; KRAS wild type MSS 6.8 PRMT5 inhibitors 7 57 M Asymptomatic (incidental imaging finding) Head Yes Not tested Not tested Not tested N/A
Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (mGEA): PD-L1 subgroup analysis from HERIZON-GEA-01.
4010 Background: In HERIZON-GEA-01 (NCT05152147), 1L zanidatamab + CT ± tislelizumab significantly improved progression-free survival (PFS) and, with tislelizumab, yielded a statistically significant overall survival (OS) benefit in HER2+ mGEA. Here we report efficacy in PD-L1 subgroups. Methods: Eligible patients (pts) with previously untreated HER2+ mGEA, irrespective of PD-L1 status, were randomized (1:1:1) to zanidatamab (1800 mg [<70 kg]/2400 mg [≥70 kg] IV Q3W) + tislelizumab (200 mg IV Q3W) + capecitabine/oxaliplatin (CAPOX) or 5-FU/cisplatin (FP); zanidatamab + CAPOX or FP; or tras + CAPOX or FP. PD-L1 expression was retrospectively assessed using the VENTANA SP263 assay according to tumor area positivity (TAP) score and combined positive score (CPS). Primary endpoints were PFS (BICR) and OS; efficacy by PD-L1 status (TAP) was prespecified. Results: With 26 mo median follow-up, PFS (HR, 0.63; P <0.001) and OS (HR, 0.72; P = 0.004) were significantly prolonged with zanidatamab + tislelizumab + CT vs tras + CT in the ITT population. In pts treated with zanidatamab + tislelizumab + CT, similarly prolonged PFS and OS were observed in PD-L1–negative and PD-L1–positive pts (Table); data were consistent between TAP and CPS. In PD-L1 TAP <1% and ≥1% pts, the 18-mo PFS was 50.3% and 42.6%, respectively, and the 24-mo OS was 63.7% and 53.5% with zanidatamab + tislelizumab + CT. In the tras + CT arm, OS was prolonged in PD-L1–positive vs –negative pts. Of note, in the tras + CT arm, 15% of pts received subsequent checkpoint inhibitors and 29% received subsequent HER2-targeted therapies vs 2% and 13%, respectively, in the zanidatamab + tislelizumab + CT arm. Additional details on these subgroups will be presented at the congress. Conclusions: In HERIZON-GEA-01, zanidatamab + tislelizumab + CT demonstrated meaningful improvements in PFS and OS in both PD-L1–positive and PD-L1–negative pts as determined by TAP or CPS. The longer OS observed with tras + CT in PD-L1–positive vs –negative pts may be at least partially explained by differences in subsequent therapies. These findings are notable as they demonstrate benefit for this regimen regardless of PD-L1 status. Clinical trial information: NCT05152147 . Zanidatamab + Tislelizumab + CT Tras + CT ITT NmPFS (95% CI), momOS (95% CI), mo 30212.4 (9.8, 18.5)26.4 (21.5, 30.3) 3088.1 (7.0, 8.9)19.2 (16.8, 21.8) TAP <1%n (%)mPFS (95% CI), momOS (95% CI), mo 90 (29.8)18.5 (9.7, 25.2)29.7 (24.7, NE) 98 (31.8)7.9 (5.8, 9.6)15.8 (12.6, 21.4) CPS <1n (%)mPFS (95% CI), momOS (95% CI), mo 78 (25.8)18.5 (9.7, 25.2)30.3 (25.7, NE) 80 (26.0)8.1 (5.8, 9.8)15.7 (12.6, 21.4) TAP ≥1%n (%)mPFS (95% CI), momOS (95% CI), mo 187 (61.9)11.3 (9.6, 18.5)26.4 (18.7, 35.9) 188 (61.0)8.3 (6.9, 9.7)21.2 (17.7, 25.2) CPS ≥1n (%)mPFS (95% CI), momOS (95% CI), mo 198 (65.6)12.3 (9.7, 18.5)26.4 (18.7, 34.6) 206 (66.9)8.2 (6.9, 9.1)20.8 (17.3, 23.9)
SOHO-01: Updated safety and efficacy of sevabertinib in patients with advanced <i>HER2</i> -mutant non-small cell lung cancer (NSCLC).
8622 Background: Sevabertinib, a potent, reversible, oral tyrosine kinase inhibitor, received FDA accelerated approval for pretreated patients with advanced NSCLC harboring HER2 tyrosine kinase domain-activating mutations. Sevabertinib demonstrated significant antitumor activity and manageable safety in patients with HER2 -mutant NSCLC who had previously received treatment (Cohort D) or were treatment-naïve (Cohort F) in the ongoing, open-label, multicenter, Phase I/II SOHO-01 trial (NCT05099172) (Le X et al. N Engl J Med 2025). Here, we report updated safety and efficacy data from Cohorts D and F. Methods: Patients with HER2 -mutant NSCLC received sevabertinib 20 mg twice daily in both cohorts: patients previously treated with systemic therapy but naïve to HER2-targeted therapy (Cohort D) and treatment-naïve patients (Cohort F). The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR) per RECIST v1.1. Other key prespecified and secondary endpoints included duration of response (DoR) and progression-free survival (PFS) assessed by BICR per RECIST v1.1, and safety per MedDRA v28.0 and CTCAE v5.0. Results: In total, 154 patients (n=81, D; n=73, F) received sevabertinib in the two cohorts; median follow-up was 19.5 (D) and 15.0 (F) months. Median age was 60 (D) and 65 (F) years; 61.7% (D) and 63.0% (F) were female; 61.7% (D) and 78.1% (F) had never smoked. As of November 17, 2025, ORR (95% CI) was 66.7% (55.3, 76.8; D) and 75.3% (63.9, 84.7; F); disease control rate (confirmed response or stable disease for ≥12 weeks; 95% CI) was 81.5% (71.3, 89.2; D) and 89.0% (79.5, 95.1; F). Median (95% CI) DoR was 9.5 (6.3, 13.5; D) and 12.2 (8.8, not estimable; F) months; median (95% CI) PFS was 8.3 (6.9, 12.3; D) and 13.5 (10.0, not estimable; F) months. Treatment-related adverse events (TRAEs) in both cohorts were consistent with previous reports. Grade 3 or higher TRAEs occurred in 39.5% (D) and 24.7% (F) of patients. Diarrhea was reported in 86.4% (D) and 87.7% (F) of patients; grade 3 diarrhea occurred in 23.5% (D) and 5.5% (F) of patients. No cases of interstitial lung disease or grade 4 diarrhea, discontinuations due to diarrhea, or new safety signals were observed. Conclusions: Sevabertinib demonstrated sustained efficacy with a manageable safety profile in treatment-naïve and pretreated patients with advanced HER2 -mutant NSCLC. These data further support the rapid and durable responses of sevabertinib for patients with HER2 -mutant NSCLC. Clinical trial information: NCT05099172 .
A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor–naïve patients with metastatic uveal melanoma.
TPS9598 Background: Uveal melanoma (UM) is the most common primary intraocular malignancy, accounting for ~90% of ocular melanomas and 5% of all melanomas. Half of patients with UM develop metastases, most commonly in the liver (~90%). The prognosis for patients with metastatic UM (mUM) is poor, with a median overall survival (OS) of ~1 year. Effective treatment options for mUM are limited, as it responds poorly to single-agent immune checkpoint inhibitors (ICIs; <10% response rate). Response rates are slightly higher with combination therapies (12%–18%), but these often have increased toxicity. Tebentafusp is FDA-approved for mUM based on survival benefit but is restricted to patients who are HLA-A*02:01 positive, and only ~10% of patients achieve an objective response. RP2 is a selectively replication-competent herpes simplex virus type 1–based oncolytic immunotherapy expressing GM-CSF, a fusogenic glycoprotein (GALV-GP-R − ), and an anti–CTLA-4 antibody-like molecule. Prior preliminary clinical data of intratumoral RP2 as monotherapy or in combination with nivolumab demonstrated a promising safety profile and anti-tumor activity with an overall response rate (ORR) of 29.4% and disease control rate of 58.8% in 17 patients with mUM, most of whom had received prior ICIs. This study will assess the efficacy and safety of RP2 + nivolumab vs ipilimumab + nivolumab in patients with ICI-naïve mUM. Methods: This is a multicenter, randomized, controlled, phase 2/3 study (NCT06581406; RP2-202). Key eligibility criteria include age ≥18 years and confirmed unresectable mUM with at least 1 lesion amenable to injection; up to 1 prior line of therapy in the metastatic setting is allowed. Patients with prior exposure to ICIs since the time of mUM diagnosis, >50% liver involvement, or previous selected liver-directed therapies are not eligible. Enrolled patients (N = ~280) will be randomized 1:1 to receive either RP2 + nivolumab or ipilimumab + nivolumab. In the RP2 + nivolumab arm, RP2 will be given intratumorally initially at 1 × 10 6 plaque-forming units (PFU)/mL, then every 2 weeks (Q2W) at 1 × 10 7 PFU/mL for 7 doses in combination with intravenous (IV) nivolumab (240 mg). In the ipilimumab + nivolumab arm, patients will receive IV ipilimumab (3 mg/kg) and IV nivolumab (1 mg/kg) Q3W for 4 doses. Patients in both arms may then receive IV nivolumab at 240 mg Q2W or 480 mg Q4W for up to 2 years. The co-primary endpoints are OS and progression-free survival by independent central review using RECIST 1.1. Secondary endpoints are ORR, duration of response, disease control rate, clinical benefit rate, duration of clinical benefit, and safety, including incidence of treatment-emergent adverse events (AEs), serious AEs, and immune-mediated AEs. Clinical trial information: NCT06581406 .
Real-world effectiveness of MET inhibitors versus immunotherapy ± chemotherapy in 1L for patients with MET exon 14 skipping mutations in non-small cell lung cancer.
8645 Background: Metastatic non-small cell lung cancer (mNSCLC) remains a leading cause of cancer-related deaths, with MET exon 14 skipping mutations (METex14) identified as a key oncogenic driver in 1%–4% of cases. MET tyrosine kinase inhibitors (TKI) such as capmatinib and tepotinib have demonstrated efficacy in clinical trials, leading to FDA approval in any treatment line. This study aims to compare first-line (1L) survival outcomes with MET TKI versus immune checkpoint inhibitors ± chemotherapy (IO ± Chemo). Methods: Patient characteristics and survival outcomes were retrospectively analyzed for METex14 mNSCLC patients who received 1L therapy with either (1) MET TKI (tepotinib and capmatinib) or (2) IO ± Chemo. Patients were excluded if they had EGFR alterations. Data were sourced from ConcertAI's Patient360 and RWD360, datasets sourced from oncology EHR in the US. Results: Among a total of 344 patients, 174 (50.6%) were > 80 years of age, 94 (87.9%) had non-squamous mNSCLC, 176 (51.2%) were female, and 71 (20.6%) had ECOG PS ≥2. As 1L, 202 received MET TKI, 61 received IO + Chemo, and 81 received IO only. Baseline clinicopathologic features were balanced except for a slightly higher proportion of patients with TPS PD-L1 ≥50 in the IO ± Chemo group ( p < 0.05). At a median follow up of 40.7 months (mo), in the overall group median progression-free survival (mPFS) was 6.6 mo (95% CI: 5.8–8.8) and median overall survival (mOS) was 15.5 mo (95% CI: 14.4–18.3). MET TKI yielded a mPFS of 7.8 mo (95% CI: 6.2–9.1) and a mOS of 13.8 mo (95% CI: 11.4–17.6). IO ± Chemo resulted in a mPFS of 5.1 mo (95% CI: 3.7–8.2) and a mOS of 21.9 months (95% CI: 15.5–25.8). The mPFS did not differ significantly between groups ( p = 0.38), while mOS favored IO ± chemotherapy ( p = 0.03). Objective response rate was 61.0% with MET TKI and 50.7% with IO ± Chemo ( p = 0.74); disease control rate was significantly higher with MET TKI (77.0% vs 64.8%; p = 0.03). In subgroup analysis, among patients with PD-L1 ≥50, OS was significantly longer with 1L IO ± Chemo compared with MET TKI (22.0 mo, 95% CI: 7.5–34.3 vs. 8.5 mo, 95% CI: 6.6–16.5; p < 0.02). In contrast, among patients with PD-L1 < 50, MET TKI was associated with longer PFS (9.2 mo, 95% CI: 4.2–11.7 vs. 4.9 mo, 95% CI: 2.1–11.0; p = 0.07) although OS was similar (17.6 mo, 95% CI: 9.6–29.6 vs. 14.5 mo, 95% CI: 4.0–23.2; p = 0.57). Conclusions: Among patients with METex14 mNSCLC, those treated with 1L IO ± Chemo had a better OS compared to those treated with MET TKI. This seems especially valid for patients with PD-L1 ≥50, for whom IO ± Chemo significantly improved OS. However, patients with PD-L1 < 50 showed prolonged PFS when treated with MET TKI. This highlights the need for personalized treatment patterns in this patient population.
Evaluation of <i>KRAS</i> -mutant circulating tumor DNA as a surgical biomarker in localized pancreatic cancer treated with multi-agent neoadjuvant chemotherapy.
e16471 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for risk stratification in localized pancreatic ductal adenocarcinoma (PDAC), but its ability to predict surgical resection and overall survival (OS) after multi-agent neoadjuvant chemotherapy (NAC) is not well defined. High-sensitivity digital droplet PCR (ddPCR) enables detection of low-frequency KRAS mutations in plasma with greater sensitivity than standard approaches, allowing noninvasive, dynamic assessment of tumor burden. We evaluated whether KRAS -mutant ctDNA detected by ddPCR predicts surgery and OS in localized PDAC. Methods: Patients with localized PDAC were enrolled in a prospective study at an academic health system from October 2020 to July 2025. Peripheral blood was collected at diagnosis, after NAC, and after surgery. Plasma was isolated for cell-free DNA extraction and probed for KRAS G12D, G12V, and G12R ctDNA using ddPCR. Multivariable logistic regression assessed the association between ctDNA detection and receipt of resection, adjusting for baseline anatomic resectability and receipt of NAC, and OS was evaluated by Kaplan-Meier. Results: This study included 247 blood samples from 123 patients, with a median follow-up of 18.6 months. Fifty-nine patients received FOLFIRINOX, 35 gemcitabine-based therapy, and 9 both; 63 underwent surgery after a median of 2.5 months of NAC. KRAS ctDNA detection rates were 66.3% at diagnosis, 61.3% post-NAC, and 56.4% post-surgery. Detection of KRAS ctDNA at diagnosis was associated with lower odds of surgery, independent of baseline resectability status (aOR 0.29, CI 0.08–0.82, p = 0.028). Among FOLFIRINOX-treated patients who underwent surgery, post-surgery KRAS ctDNA detection was associated with shorter OS (median OS [mOS] 30.2 vs not reached [NR], p = 0.012), whereas no association was observed in gemcitabine-treated patients (mOS 24.2 vs 37.4 months, p = 0.567). Among 30 patients completing adjuvant chemotherapy (AC), ctDNA detection after FOLFIRINOX and surgery remained associated with inferior OS (30.2 months vs NR, p = 0.023), with ctDNA clearance after AC observed in only a third of patients after a median of 2.7 months of treatment. Conclusions: In this prospective cohort of localized PDAC, the prognostic value of KRAS -mutant ctDNA detected by ddPCR varied by NAC regimen. KRAS ctDNA detection at diagnosis predicted lower odds of surgery after NAC, regardless of resectability status, consistent with poor tumor biology. The prognostic impact of post-surgery KRAS ctDNA differed by NAC regimen, with inferior OS among ctDNA-positive patients treated with FOLFIRINOX. The use of AC did not change prognosis, suggesting ddPCR identifies patients with persistent KRAS ctDNA after NAC who are unlikely to benefit from additional chemotherapy and may be better served by treatment with novel KRAS -targeted agents.
Lumbar puncture in thrombocytopenic adults with leukemia and lymphoma revisited: A scoping review.
e18612 Background: Patients with hematological malignancies may require a lumbar puncture (LP) for evaluation of central nervous system involvement as well as for intrathecal injection of chemotherapy. Severe thrombocytopenia in these patients can increase the risk of bleeding complications, and current guidelines recommend avoidance of LP in patients with thrombocytopenia below 50 ×10⁹/L. This review aims to re-evaluate the safety of LP in adults with hematologic malignancies in the setting of thrombocytopenia. Methods: Literature was reviewed in PubMed, Scopus, and Google Scholar for eligible articles. Inclusion criteria were adults above 18 with leukemia or lymphoma who required LP or intrathecal injection of chemotherapy with thrombocytopenia. Exclusion criteria were pediatric population, bone marrow transplant patients, and non-English articles. Two reviewers independently screened studies for eligibility and extracted data. Results: Eight observational studies met the inclusion criteria. The studies included >66,000 patients with LP with >4,700 LP performed at platelet counts <50 ×10⁹/L without a significant increase in bleeding. Conclusions: The studies of lumbar puncture and thrombocytopenia were heterogeneous; they included both adult and pediatric populations, as well as studies combining hematologic and solid malignancies. Despite these limitations, retrospective data suggest that LP performed at platelet counts below 50 ×10⁹/L is associated with a higher rate of traumatic taps, without a corresponding increase in clinically significant hemorrhagic complications. Importantly, LP was reported to be safe below platelet counts of 40×10⁹/L, supporting consideration of a lower platelet threshold at 40 ×10⁹/L. Studies evaluating lumbar puncture safety in thrombocytopenic adults with hematologic malignancies. Article Number of Patients / LPs Platelet Count at LP Outcome Vavricka et al., 2003 66 20–30 (35 LPs), 31–50 (40), 51–100 (43), >100 (77) no hemorrhagic complications; more traumatic LPs at lower platelet counts Öztürk et al., 2021 42 <100k in 41%; <50k in 18%; untransfused LPs <30k (7 ) No hematoma after LP Chung et al., 2020 Adults 871; Peds 266 <50 ×10⁹/L: 110 LPs; ≥50 ×10⁹/L: 2,149 LPs Platelets <50 ×10⁹/qaL did not increase complications Jordan et al., 2023 900 LPs ≥50 ×10⁹/L: 682 LPs; <50 ×10⁹/L: 218 LPs Lowering threshold <50 ×10⁹/L did not increase bleeding; higher traumatic taps at lower counts Corrao et al., 2025 345 <40k: 39 LPs; 40–49k: 120; ≥50k: 1,073 4 hematomas total; lowering the threshold to 40k did not increase bleeding risk Ning et al., 2016 135 patients; 369 LPs ≤50 ×10⁹/L: 28 LPs No hemorrhagic complications; traumatic taps similar across groups Portuguese et al., 2020 262 ≤50 ×10⁹/L: 19 LPs Severe thrombocytopenia increased traumatic taps; no significant bleeding Bodilsen et al., 2020 64,730 <50 ×10⁹/L: 4,236 LPs Traumatic taps are common; major bleeding not reported
Smoking prevalence as a predictor of preventable cancer burden: A mediation analysis with health systems performance in 167 nations (2008–2023).
e22678 Background: Smoking prevalence and cancer mortality relationships vary significantly across healthcare systems. Healthcare access may mediate smoking's effects on malignancy mortality, but this pathway remains incompletely characterized. We examine smoking prevalence as a predictor of age-standardized cancer mortality while quantifying direct effects and indirect pathways through health system capacity. Methods: A 16-year prospective study of 167 nations (2008–2023) integrated: adult smoking prevalence (%) from WHO, age-standardized cancer mortality (per 100,000) from Global Burden of Disease 2023, health system efficiency index (HSEI, 0–100), and healthcare expenditure (% GDP). Mixed-effects regression with regional random intercepts modeled cancer mortality as a function of lagged smoking prevalence (t–2 years), controlling for HSEI, expenditure, and income. Mediation analysis decomposed effects into direct (smoking to mortality) and indirect (smoking to health systems to mortality) pathways using natural effects estimators. Two-way prevalence*HSEI interactions were tested with variance estimation and country-level clustering. Results: Among 2,672 country-year observations, baseline smoking prevalence (mean 24.3%, SD 11.8%) predicted cancer mortality (mean 96.4/100,000, SD 54.2). A 10-point prevalence increase independently predicted 8.7 additional cancer deaths per 100,000 (95% CI: 6.2–11.3; p < 0.001). Direct effect: 64% (5.6/100,000; 95% CI: 3.8–7.4); indirect effect: 36% (3.1/100,000; 95% CI: 1.9–4.3). HSEI significantly modified associations: systems with HSEI ≥75 (n = 48) showed 2.9/100,000 effect (95% CI: 0.4–5.4), while HSEI < 50 (n = 67) showed 11.2/100,000 (95% CI: 8.1–14.3)—a 3.9-fold difference. Regional intercepts ranged –12.4 (Asia-Pacific) to +18.6 (sub-Saharan Africa). Seventy-three percent of nations showed significant prevalence-mortality associations (p < 0.10). Model R² was 0.58 (within-country) and 0.84 (between-country). Conclusions: Smoking prevalence exerts substantial independent effects on cancer burden; approximately one-third operates through health system deficiencies. Strengthening oncology and primary prevention infrastructure may reduce smoking-attributable cancer mortality by 30–45% independent of prevalence reductions, particularly in resource-limited settings. Health system efficiency improvements offer potential for 3.8 per 100,000 annual mortality reduction despite unchanged smoking rates.
Association of cardiovascular toxicities with bispecific antibody therapy in patients with hematologic malignancies: A single-center retrospective analysis.
e19014 Background: Bispecific antibodies (bsAbs) are an emerging treatment for hematologic malignancies, but data on cardiovascular (CV) toxicity profile of bsAbs is scarce. Our aim was to assess the incidence, timing, and types of CV toxicities among bsAb-treated patients at the University of Oklahoma Health Sciences Center. Methods: We conducted a single-center retrospective review of 49 adults who received outpatient bsAb therapy for hematologic malignancies at the Stephenson Cancer Center between July 2023 and March 2025. Data on baseline CV comorbidities, biomarkers (BNP, troponin), ICU admissions, and cardiopulmonary interventions were extracted from medical records. Cardiotoxicity was defined as biomarker elevation, new or worsening heart failure, arrhythmia, or ICU-level cardiopulmonary support. Results: Pre-existing CV comorbidities included hypertension (49%), atrial fibrillation/flutter (18%), and heart failure (10%). Cardiopulmonary symptoms included dyspnea (18.4%), peripheral edema (8.2%), chest pain (6.1%), and lower extremity swelling (4.1%). DVT and PE occurred in 4.1% each. New-onset hypertension occurred in 4.1%, and 2.0% had QT prolongation, atrial fibrillation/flutter, supraventricular arrhythmia, ventricular arrhythmia, or heart failure. Single cases (2.0%) were also observed for myocardial infarction, pericardial effusion, heart failure exacerbation, pulmonary edema, DIC, vasculitis, vascular aneurysm/stenosis/rupture, shock, and cardiac arrest. BNP was elevated in 32%, often >2000 pg/mL, typically in the setting of CRS, infection, or volume overload. Troponin elevation occurred in 6%, without clear MI. ICU admissions occurred in 9 of 48 patients (18.8%), with vasopressors used in 5 (10.4%). No patients required invasive mechanical ventilation, and 40% required inpatient cardiopulmonary support (oxygen, BiPAP, or HFNC); none needed new home oxygen at discharge. 2 (4.2%) had cardiology-related hospital admissions. Conclusions: bsAb therapy was associated with a diverse spectrum of CV toxicities, particularly dyspnea, elevated BNP, and cardiopulmonary compromise. Although arrhythmias and troponin-defined myocardial injury were less frequent, they remain clinically relevant. These findings support the need for active cardiovascular surveillance during bsAb treatment, particularly in patients with underlying CV disease.
Clinical outcomes for low-income patients with early-onset colorectal cancer: An analysis of the National Inpatient Sample.
e15697 Background: Despite recent global decreases in overall cancer incidence, the incidence of early-onset colorectal cancer (EOCRC) is steadily increasing in western populations. Limited data is available on the comorbid correlations for this unfortunately expanding population. We sought to examine the National Inpatient Sample (NIS) to describe in-hospital outcomes among low-income patients with EOCRC. Methods: Data were extracted from the NIS from the years 2019 and 2020. The NIS was searched for hospitalizations of adult patients with EOCRC, defined as all-cause colorectal cancer in patients 50 years old or younger. We then examined the outcomes of patients with the lowest incomes, or with a self-reported annual income of $50,000 or less. Propensity score matching was used to adjust for confounders and the primary outcome was inpatient mortality. SPSS software was used for statistical analysis and all values were powered to p < 0.001. Results: This study included 11,820 patients with EOCRC, of which 3,254 (27.5%) were identified as low income. Propensity score matching showed that low income patients with EOCRC had higher inpatient mortality (OR 1.488, CI 1.379-1.606, p < 0.001). On secondary analysis, low income EOCRC patients were more likely to have anemia (OR 1.457, CI 1.430-1.485), thrombocytopenia (OR 1.434, CI 1.367-1.504), hypertension (OR 1.676, CI 1.555-1.808), acute renal failure (OR 1.491, CI 1.436-1.547), pancreatitis (OR 1.394, CI 1.232-1.578), pericarditis (OR 1.471, CI 1.259-1.718), esophagitis (OR 1.423, CI 1.382-1.465), Crohn’s disease (OR 1.360, CI 1.230-1.504), severe liver disease (OR 1.407, CI 1.380-1.436), metastatic disease (OR 1.393, CI 1.374-1.412), secondary lymphomas (OR 1.488, CI 1.183-1.773), all-cause arrhythmias (OR 1.400, CI 1.301-1.506), all-cause shock (OR 1.477, CI 1.310-1.665), all-cause sepsis (OR 1.464, CI 1.421-1.509), all-cause coagulopathy (OR 1.364, CI 1.295-1.436), all-cause heart failure (OR 1.661, CI 1.508-1.828), all-cause stroke (OR 1.461, CI 1.345-1.586), and all-cause myocardial infarction (OR 1.596, CI 1.405-1.811). Conclusions: In this nationally representative, population‐based retrospective cohort study, low-income patients with EOCRC were associated with higher mortality and worse outcomes.
ProTACT: Preliminary data from a first-in-human, phase 1 study evaluating the safety, tolerability, and anti-tumor activity of [ <sup>225</sup> Ac]Ac-FL-020, a PSMA-targeted radioconjugate, in patients with mCRPC.
5050 Background: [ 225 Ac]Ac-FL-020 is a next-generation, prostate-specific membrane antigen (PSMA) alpha radioconjugate developed using the proprietary UniRDC linker-chelator technology designed to optimize biodistribution. [ 225 Ac]Ac-FL-020 is intended for treating patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and aims to enhance tumor uptake while sparing radiosensitive organs, such as salivary glands, thus potentially leading to an improved therapeutic window. Methods: ProTACT (FL-020-001) is a first-in-human, open-label, multicenter Phase 1 study investigating the safety, tolerability, and preliminary anti-tumor activity of [ 225 Ac]Ac-FL-020 in pts with advanced PSMA-positive mCRPC. This study consists of: Bayesian dose escalation (Part 1) and dose expansion (Part 2). Eligible pts must have: histologically confirmed mCRPC, evidence of disease progression, and ≥1 PSMA-positron emission tomography positive lesion (uptake higher than liver). Prior androgen receptor signaling inhibitors or CYP17 inhibitors and ≥1 taxane-based chemotherapy is required, unless declined by the pt. Prior Lu-177 is allowed. Pts with extensive PSMA-negative disease are excluded. Dose cohorts of 1 to 3 pts (for Cohorts 1 and 2) and dose cohorts of 3 to 6 pts (for Cohorts 3+) will evaluate ascending dose levels from 1 to 10 MBq (intravenous; every 6 weeks; x 6 cycles) to determine the maximum tolerated dose and/or recommended Phase 2 dose (RP2D). Once the RP2D is established, 18 additional pts will be enrolled in Part 2 to further assess safety and early signals of efficacy. Results: As of 2 Jan 2026, 15 eligible pts have received [ 225 Ac]Ac-FL-020 (maximum dose/cycle: 5 MBq). No dose-limiting toxicities have been observed. Most frequent adverse events (AEs) were fatigue (10 pts), nausea and dry mouth (7 pts each), constipation and anemia (4 pts each). Grade (G)3+ AEs were reported for 6 pts, all G3+ AEs occurred in one pt each. One pt at 1 MBq had G3 anemia and 1 pt at 5 MBq had G3 anemia and G3 thrombocytopenia, both considered related to disease progression with bone marrow infiltration and unrelated to [ 225 Ac]Ac-FL-020. As of the cutoff date, 11 pts remain on treatment and 4 pts discontinued treatment prematurely, 3 due to disease progression and 1 due to G2 dry mouth. Another 6 pts reported dry mouth, all were G1. No renal toxicities or decline in renal function was observed. As of 6 Jan 2026, 1 of 3 pts at 3 MBq showed a reduction in baseline prostate-specific antigen (PSA) > 80% after 3 cycles and 2 of 6 pts at 5 MBq showed a reduction in PSA > 50% after 1 cycle. Conclusions: These initial findings support the feasibility and tolerability of [ 225 Ac]Ac-FL-020 administration in heavily pretreated pts with mCRPC with a few notable PSA responses. The RP2D has not yet been reached, and dose escalation continues. Clinical trial information: NCT06492122 .
First-line induction oxaliplatin-based chemotherapy followed by maintenance in isolated peritoneal metastatic colorectal cancer: Real-world outcomes from Vietnam.
e15524 Background: Isolated peritoneal metastatic colorectal cancer (IPM-CRC) represents a rare and biologically unique entity characterized by poor survival. Although cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been explored, its survival benefit remains inconsistent, and systemic chemotherapy continues to represent the cornerstone of treatment. This population remains an underrepresented cohort in clinical research and is frequently pooled with other metastatic patterns, particularly in low- and middle-income settings where access to CRS/HIPEC is limited. We conducted this study to evaluate real-world outcomes of first-line induction oxaliplatin-based chemotherapy followed by maintenance therapy in patients with IPM-CRC. Methods: This ambispective, single-center cohort included 94 patients with IPM-CRC treated in Vietnam between 2019 and 2025. All patients received first-line oxaliplatin-based induction chemotherapy (CAPEOX or FOLFOX ± bevacizumab) and subsequently received maintenance therapy with capecitabine ± bevacizumab after 4–6 months of induction upon achieving partial response or stable disease. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Response was evaluated using a dual approach: the objective response rate (ORR) per RECIST v1.1 in patients with measurable disease on imaging, and clinical benefit (symptom improvement or disease stabilization) in those without measurable lesions. The disease control rate (DCR) combined both measures. Adverse events (AEs) were graded per CTCAE v5.0. Results: The median age was 57 (range 18-78) years, with 72.3% male. Bevacizumab was administered in 79.8% of patients. With a median follow-up of 18.1 (95%CI 13.9-22.2) months, the median PFS and OS were 9.5 (95%CI 8.1-11) and 28.2 (95%CI 20.4-36.1) months, respectively. Among 55 patients evaluable for response assessment per RECIST v1.1, ORR was 32.9%. Across the full cohort, overall DCR was 75.5%; DCR was 78.7% among patients receiving bevacizumab and 63.2% among those treated without bevacizumab. The median duration of maintenance therapy was 7.9 (IQR 3.7-16.0) months. Grade 3–4 adverse events occurred in 13.8% of patients, most commonly neutropenia (11.7%). No treatment-related deaths were observed. Conclusions: This induction-to-maintenance approach demonstrates meaningful activity and feasibility in patients with IPM-CRC, even within a resource-limited setting. Continued analyses will help determine which patients benefit most.
IMbrave251: Final analysis of atezolizumab (atezo) + lenvatinib (lenva) or sorafenib (sora) vs lenva or sora alone in locally advanced or metastatic hepatocellular carcinoma (LA/mHCC) previously treated with atezo and bevacizumab (bev).
4002 Background: Several immuno-oncology therapies are available for 1L HCC, but data are limited after progression. IMbrave251 (NCT04770896) is the first global randomized Phase 3 trial to assess atezo + lenva or sora (TKIs) vs lenva or sora alone in patients (pts) with LA/mHCC that progressed after atezo + bev treatment (tx). This is the final analysis. Methods: Eligible pts had LA/mHCC that was responsive to atezo + bev tx but then progressed (atezo + bev was given for ≥4 cycles and ≥2 tumor assessments, of which ≥1 showed stable disease or complete/partial response). In the atezo + TKI arm, pts received atezo (1200 mg Q3W) + lenva (8 mg for pts < 60 kg or 12 mg for pts ≥60 kg QW) or sora (800 mg QW). Pts in the TKI-only arm received lenva or sora alone. The primary endpoint was OS. Secondary endpoints included PFS, ORR by RECIST 1.1, DOR, time to tumor progression (TTP), quality of life, and safety. Stratification factors were disease etiology (hepatitis B/C infection vs non-viral), ALBI score (1 vs 2/3), AFP ( < 400 vs ≥400 ng/mL), and TKI therapy (lenva vs sora). Results: IMbrave251 enrolled 557 pts (full analysis population). Median duration of follow-up was 12 mo. Pts were assigned to receive atezo + TKI (n = 279) or TKI-only (n = 278). Most pts in both arms received lenva (92.1%) vs sora (7.9%). At clinical cutoff (Oct 10, 2025), median (m)OS with atezo + TKI vs TKI-only was 14.6 vs 12.5 mo (stratified HR 0.88; P = 0.2115) and mPFS was 4.3 vs 4.8 mo (stratified HR 1.05), respectively. Confirmed ORR was 7.5% vs 5.8% with atezo + TKI vs TKI-only. DOR was 10.2 vs 6.9 mo, respectively (stratified HR 0.47) (Table). Additional subgroup analyses and complete duration of systemic therapy will be shown. In the atezo + TKI vs TKI-only arm, the median tx duration was 5.6 vs 4.7 mo for lenva and 2.9 vs 2.3 mo for sora. No new or unexpected safety signals were seen (safety analysis n = 554; Table). Conclusions: IMbrave251 did not meet its primary OS endpoint but showed that the addition of atezo to TKIs had a manageable safety profile. This study provides clinically relevant Phase 3 evidence addressing an important, unanswered clinical question regarding 2L tx sequencing after immunotherapy and establishes a new OS benchmark for 2L tx in LA/mHCC. Clinical trial information: NCT04770896 . Efficacy (95% CI) Atezo + lenva or sora(n=279) Lenva or sora(n=278) Stratified HR (95% CI) mOS, mo 14.6 (12.6, 16.8) 12.5 (10.7, 15.5) 0.88 (0.72, 1.08) P =0.2115 mPFS, mo 4.3 (4.1, 5.4) 4.8 (4.2, 5.6) 1.05 (0.88, 1.25) ORR, % 7.5 (4.7, 11.3) 5.8 (3.3, 9.2) Δ1.77 (−2.72, 6.26) a mDOR, mo 10.2 (5.6, 13.0) 6.9 (5.5, 11.7) 0.47 (0.18, 1.23) mTTP, mo 4.4 (4.2, 5.5) 5.4 (4.2, 5.6) 1.06 (0.87. 1.28) Safety, n (%) n=279 n=275 Grade 3/4 | 5 AE 207 (74.2) | 15 (5.4) 182 (66.2) | 16 (5.8) - Serious AE | AE leading to withdrawal from any study drugs 112 (40.1) |33 (11.8 101 (36.7) |19 (6.9) - a Difference in confirmed ORR (95% CI).
Platinum rechallenge versus non-platinum regimens as second-line treatment for advanced thymoma: Analysis of the largest retrospective cohort to date.
8117 Background: Although guidelines list platinum-based combination chemotherapy (Pt-rechallenge) as a second-line strategy for patients with thymoma ineligible for curative-intent therapy, evidence is limited to small case series. We investigated the efficacy of Pt-rechallenge versus non-platinum regimens in the largest retrospective cohort of second-line thymoma treatment reported to date. Methods: This multicenter study analyzed patients treated at 39 Japanese institutions. Of 157 patients ineligible for curative-intent therapy who initiated palliative platinum-based chemotherapy (2000–2020), 91 patients receiving second-line systemic cytotoxic chemotherapy were evaluated. Efficacy outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were compared between second-line Pt-containing (Pt-rechallenge) and non-platinum (non-Pt) regimens. Results: Among the 91 patients (median age 59; 91% ECOG PS 0-1) with a median follow-up of 1056 days, 64 (70%) received Pt-rechallenge and 27 received non-Pt regimens (S-1 [tegafur/gimeracil/oteracil], n=15; pemetrexed, n=6; amrubicin, n=5; paclitaxel, n=1). First-line ORR was 51%, and the median chemotherapy-free interval from first-line chemotherapy was 394 days. Pt-rechallenge achieved a significantly higher ORR than non-Pt chemotherapy (40% vs 5%; p=0.0012). Regarding survival outcomes, median PFS was 8.8 months (95% CI, 5.9–11.9) in the Pt-rechallenge group vs 8.0 months (95% CI, 4.8–30.4) in the non-Pt group (HR, 1.29; 95% CI, 0.77–2.18; p=0.325). Median OS was 70.6 months (95% CI, 53.5–82.4) vs 64.4 months (95% CI, 38.7–not estimable) (HR, 1.12; 95% CI, 0.53–2.37; p=0.759); differences in PFS and OS were not statistically significant. In the Pt-rechallenge cohort, outcomes were stratified by anthracycline (A) use in 1st/2nd-line (A→A, n=17; A→non-A, n=28; non-A→A, n=12; non-A→non-A, n=7): ORRs were 50%, 35%, 27%, and 29%; median PFS were 9.3 (95% CI, 4.5–12.2), 6.4 (95% CI, 4.6–10.6), 21.0 (95% CI, 8.7–41.9), and 4.1 (95% CI, 1.8–9.3) months, respectively. Stratified by platinum-free interval (PFI) (<6 months, n=15; 6–12, n=10; 12–36, n=27; ≥36, n=12), ORR were 14%, 63%, 46%, and 20%; median PFS were 5.8 (95% CI, 1.8–19.8), 7.3 (95% CI, 2.1–14.5), 10.3 (95% CI, 5.5–23.5), and 9.0 (95% CI, 3.1–16.9) months. Conclusions: In this largest comparative study to date, platinum rechallenge demonstrated superior response rates compared to non-platinum regimens, particularly in patients with favorable PFI. Study registration: UMIN000048181.
Oral mannitol for chemotherapy-induced constipation (CIC): A randomized, multicenter, controlled study.
12146 Background: Chemotherapy-induced constipation (CIC) is a common yet frequently overlooked supportive care issue, currently, there is still a lack of efficient and affordable methods. This trial was designed to compare the efficacy and safety of orally administered mannitol injection versus lactulose in cancer patients with CIC. Methods: An open-label, multicenter, prospective RCT (ChiCTR2200056847) planned to enroll 114 adults. Participants were randomized 1:1 to oral mannitol 50 mL post-meal 3–5×/day or lactulose 30 mL once daily for 3 days. Primary endpoint: time to first spontaneous defecation (TFSD). Secondary endpoints included weekly complete spontaneous bowel movements (CSBMs), Bristol Stool Form Scale, PAC-QOL, and CTCAE v5.0 adverse events (AEs). Interim analysis was performed when 112 participants had completed the 7-day assessment; database was locked on 30 January 2026. Results: A nationwide survey (14 provinces, n=1,174) revealed significantly higher constipation rates in stage IV cancer patients (p<0.05), and found that the managements vary in effectiveness. In an RCT interim analysis (112 patients), baseline demographics were balanced between mannitol (n=56) and lactulose (n=56) groups. Median time to first defecation was significantly shorter in mannitol group with 5.5 hours (IQR 3.0-15.8) than in lactulose with 16.0 hours (IQR 5.3-27.5) (p=0.003)(Fig. 1). Secondary outcomes were comparable: weekly mCSBMs (3.0 vs. 3.0, p=0.083); Bristol Scale improvement ≥1 category (60.7% vs. 58.9%, p=0.847); and PAC-QOL score (-26 vs. -18 points, p=0.105). Both treatments were safe, with only mild, transient adverse events at similar rates (3.6% vs. 5.4%, p=0.647)(Table 1). Conclusions: Survey data confirm under-recognition of CIC and therapeutic gaps for advanced-stage patients. In this interim analysis, oral mannitol significantly shorten TFSD than lactulose, with mild adverse events, which is a rapid-onset, low-cost option for CIC management. Clinical trial information: ChiCTR2200056847. TFSD, weekly CSBMs, adverse events, PAC-QOL. Outcome Mannitol (n=56) Lactulose (n=56) p-value TFSD (median, IQR) 5.5 (3.0–15.8) hrs 16.0 (5.3–27.5) hrs 0.003 Weekly CSBMs (median, IQR) 3.0 (3.0–4.0) 3.0 (2.0–3.0) 0.083 Stool form improvement (≥1 Bristol) 34 (60.7%) 33 (58.9%) 0.847 PAC-QOL change (Δ, mean) -26 (18.3–40.5) -18 (12.5-37.5) 0.105 Any AE (%) 2 (3.6%) 3 (5.4%) 0.647