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Association of drug industry payments to oncologists and use of guideline-preferred cancer treatments.
11059 Background: Payments from the drug industry to oncologists are common and influence physicians’ prescribing decisions. However, whether payments affect the likelihood that patients receive optimal cancer treatment has not been assessed. Methods: This was a population-based cohort study. We used fee-for-service Medicare claims to identify patients with incident cancer diagnosis (new cancer diagnosis code after >= 1 year with no cancer diagnosis codes) from 2014-2020. We used National Comprehensive Cancer Network (NCCN) Guidelines to identify treatment scenarios (e.g., metastatic melanoma, stage III colon adjuvant therapy) with variation in the clinical benefit among recommended treatment options. The patient cohort corresponding to each scenario was identified using claims. We used NCCN Guidelines to identify the “optimal” treatment for each scenario (defined as the designated “preferred” treatment, with NCCN Evidence Blocks scores used for tiebreaks) at each time point across the study period. The primary outcome was whether a patient received the treatment that was, as of their diagnosis date, the optimal treatment for their cancer (vs. any non-optimal treatment). The primary exposure[s] were whether a patient’s medical oncologist received personal (“general”) payments (source: linked Open Payments data) related to 1) optimal treatment or 2) any non-optimal treatment, during the year prior to the patient’s cancer diagnosis. We fit Poisson-family generalized estimating equations, with physician-level clustering and adjustment for scenario, year, and patient characteristics, to estimate the relative risk (RR) of optimal treatment. Results: There were 14 clinical scenarios comprising 15,835 patients. There were 3,429 (21.7%) patients whose oncologist received payment for the optimal treatment, 4,891 (30.9%) for non-optimal payments, and 1,993 (12.6%) to both payment types. Oncologist receipt of payment for optimal treatment was associated with a greater likelihood (RR=1.07, 95%CI:1.01-1.13), and payment for non-optimal treatment was associated with lower likelihood (RR= 0.94, 95%CI:0.89-0.98) of patients receiving optimal treatment. Associations became stronger as payment dollar value increased; for optimal payments ≥$10,000, RR=1.26 (95%CI:1.02-1.57), and for non-optimal payments ≥$10,000, RR=0.70 (95%CI: 0.49-1.00). An estimated 41.6% of unexposed patients received optimal treatment; versus 52.6%, 29.3%, and 33.8% among patients exposed to ≥$10,000 of payments for optimal treatment only, ≥$10,000 non-optimal payments only, and ≥$10,000 of both payment types, respectively. Conclusions: Industry payments related to the optimal cancer treatment were associated with increased use of the optimal treatment. However, payments related to non-optimal treatments were more common and were associated with decreased use of optimal treatment.
The efficacy of concurrent chemoradiotherapy with/without nimotuzumab in high-risk patients with locally advanced head and neck squamous cell carcinoma after surgery: A real-world study.
e18002 Background: Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) harboring high-risk pathological features after radical surgery face high recurrence rates. This real-world study evaluated the efficacy and safety of concurrent chemoradiotherapy (CCRT) with or without nimotuzumab in this postoperative population. Methods: LA-HNSCC patients with high-risk features after surgery were stratified: those with extranodal extension (ENE) or positive/insufficient margins received nimotuzumab plus CCRT (NCCRT; extremely high-risk), while those with other high-risk factors (e.g., pT3–4, N2–3) received CCRT alone (intermediate high-risk). All received intensity-modulated radiotherapy with weekly cisplatin. Overall survival (OS) was the primary endpoint; event-free survival (EFS) and safety were secondary. Results: A total of 75 patients were enrolled (CCRT: n=50; NCCRT: n=25). The median follow-up time was 29.80 months (95% confidence interval [CI]: 25.83–33.77) in the CCRT group and 30.23 months (95% CI: 25.07–35.40) in the NCCRT group. The 2-year EFS rates were 74.1% and 60.6%, and the 2-year OS rates were 85.6% and 83.6%, respectively. Univariate analysis revealed that the platelet-to-lymphocyte ratio (PLR) and the hemoglobin-albumin-lymphocyte-platelet (HALP) score were significantly associated with OS in the CCRT group (P=0.019 and P=0.009, respectively). Treatment-related adverse events were predominantly grade 1–2, including radiodermatitis, oral mucositis, and hematologic toxicities, with no significant increase in severe toxicities observed in the NCCRT group. Conclusions: Risk-stratified adjuvant CCRT with or without nimotuzumab demonstrates promising efficacy and acceptable safety in high-risk postoperative LA-HNSCC. PLR and HALP may serve as prognostic biomarkers in intermediate-risk patients, aiding postoperative surveillance.
Early-onset cancer signature (EOCS): Pan-cancer molecular alterations with prognostic significance in early-onset (EOC) and late-onset (LOC) cancer.
3126 Background: Early-onset cancer (EOC) is an emerging global epidemic with biological and molecular features distinct from late-onset cancer (LOC). Improved delineation of genomic pathway aberrations in EOC is essential to inform risk stratification and therapeutic decision-making. However, large-scale, unbiased analyses of biological drivers across tumour types remain limited. To address this gap, we developed a pan-cancer Early-Onset Cancer Signature (EOCS) to advance understanding of the genomic architecture underpinning EOC. Methods: The AACR GENIE v16 dataset comprising 241,551 tumour samples was analysed, including 22,408 early-onset cases (≤40 years) and 219,143 late-onset cases (≥41 years) from multiple international repositories. Differentially enriched genomic alterations and pathways between EOC and LOC were identified to define the EOCS. The EOCS was subsequently evaluated across TCGA pan-cancer datasets and validated in independent cohorts, including METABRIC (breast cancer), MSKCC colorectal cancer, and MSKCC prostate cancer datasets. Results: Analysis of the AACR GENIE cohort revealed that the most significantly enriched alterations in EOC compared with LOC were CCDC6 (20% vs 10%), SYNE1 (8% vs 6%), BRAF (9% vs 6%), FLI1 (19% vs 0.5%), and EML4 (8% vs 4%). In contrast, alterations significantly enriched in LOC included KRAS (15% vs 5%), TP53 (38% vs 29%), EGFR(15% vs 5%), STK11 (3% vs 1%), and CDKN2A (10% vs 6%). Gene set enrichment analysis of EOCS-associated genes identified DNA recombination, regulation of histone H3K9 trimethylation, and homologous recombination–mediated double-strand break repair as the top three enriched Gene Ontology pathways. The EOCS was altered in 30% (3,736/10,967) of TCGA pan-cancer samples, with the highest prevalence observed in endometrial, skin, carcinosarcoma, and gastric cancers. The most frequently altered genes included SYNE1(12%), CTNNB1 (4%), PPMD1 (3%), BCR (3%), ETV6 (3%), RAD52 (3%), and H3-3A (3%). Across TCGA pan-cancer and tumour-specific cohorts, EOCS alterations were consistently associated with inferior overall survival irrespective of age at diagnosis, including pan-cancer (68 vs 83 months; p = 9.1 × 10⁻³), breast cancer (142 vs 164 months; p < 0.04), colorectal cancer (45 vs 56 months; p = 1.75 × 10⁻⁴), and prostate cancer (56 vs 77 months; p = 2.0 × 10⁻⁴). Conclusions: This pan-cancer Early-Onset Cancer Signature identifies distinct genomic pathways driving tumourigenesis in EOC. The findings provide novel biological insights into disease pathogenesis and highlight potential diagnostic and therapeutic targets, supporting the clinical relevance of EOCS across multiple cancer types.
Alignment of Vietnam’s national Essential Medicines List with cancer incidence and the WHO EML.
e23052 Background: Essential Medicines Lists (EMLs) are key policy instruments for ensuring equitable access to cancer treatment. We assessed whether the Vietnam National EML (nEML) aligns with the country’s cancer burden, and the World Health Organization (WHO) EML. Methods: Cancer medicines and indications were extracted from the 2023 WHO EML, matched to Vietnam’s national cancer incidence using GLOBOCAN 2022 data, and then compared to medicines listed on Vietnams’ nEML. Recognizing that most patients in Vietnam present with incurable disease, we assume all incident cases have a potential indication for treatment. We quantified the proportion of patients in Vietnam that could be treated if all nEML listed medicines were available. We then estimated the proportion of patients with at least one available NCCN preferred regimen based on the nEML. Our analysis focused on the top 10 incident cancers in Vietnam, and selected cancers of policy relevance (cervical cancer, testicular cancer, Hodgkin and non-Hodgkin lymphoma). Results: Of 65 cancer drugs listed in the WHO EML, 29 (44.6%) were included in Vietnams’ nEML, while one non–WHO EML drug (mitomycin) was included. Among the top 10 incident cancers in Vietnam, no nEML drugs were listed for liver or thyroid cancer where systemic therapies have limited therapeutic benefit. Paclitaxel and capecitabine, two drugs with potential indications in more than 40% of patients with cancer, are not listed on the Vietnam nEML. Among drugs with potential indications in > 10% and > 5% of patients with cancer, 9/20 (45.0%) and 15/28 (53.6%) were listed on the nEML, respectively. Among the top 10 cancers and 4 cancers of special interest, only 5/14 (35.7%) had all drugs for at least one NCCN preferred first-line regimen included in the nEML. Conclusions: A substantial gap exists between Vietnam’s nEML and the national cancer burden. The current nEML only supports a minority of NCCN preferred first line regimens for common cancers in Vietnam. We identified several low-cost drugs that could potentially benefit a large proportion of the population and should be considered in future iterations of Vietnam’s nEML.
Graft and infectious outcomes following immune checkpoint inhibitor exposure in kidney transplant recipients with non-melanoma skin cancer: A multicenter real-world study.
e21563 Background: Kidney transplant recipients (KTRs) face a disproportionately high risk of non-melanoma skin cancer (NMSC) due to chronic immunosuppression. While immune checkpoint inhibitors (ICIs) have revolutionized NMSC management, their use in KTRs remains controversial due to high rates of allograft rejection (40%–50%) reported in small, retrospective series. Real-world evidence characterizing both graft and infectious outcomes in KTRs with NMSC remains limited. We utilized a large multicenter database to evaluate outcomes in KTRs receiving ICI therapy. Methods: This retrospective cohort study used de-identified EHR data from the TriNetX Research Network. Adult KTRs with NMSC (2018-2025) were identified and stratified by ICI exposure. Patients treated with any ICI (PD-1/PD-L1/CTLA-4) were compared with ICI-naïve controls. Propensity score matching was performed for demographics, baseline kidney function, immunosuppression regimen, comorbidities, and cancer severity proxies. Outcomes assessed over 730 days of follow-up included graft rejection/failure, dialysis utilization, transplant complications, acute care utilization, and a composite opportunistic/viral infection endpoint. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: After matching, each cohort included 113 patients. ICI exposure was associated with significantly higher risk of graft rejection or failure (19.5% vs 9.7%; HR 2.43, 95% CI 1.17-5.02, p = 0.01) and opportunistic/viral infections (21.2% vs 13.3%; HR 2.08, 95% CI 1.09-3.99, p = 0.02). ICI therapy was also associated with increased transplant-related complications (35.4% vs 30.1%; HR 1.59, 95% CI 1.00-2.53, p = 0.05) and acute care utilization (61.1% vs 48.7%; HR 1.72, 95% CI 1.20-2.47, p < 0.01). Dialysis utilization was numerically higher in the ICI cohort (19.5% vs 14.2%; HR 1.59, 95% CI 0.83-3.03) but did not reach statistical significance (p = 0.16). Table 1. Conclusions: In this propensity-matched real-world cohort of KTRs with NMSC, ICI therapy was associated with approximately two-fold higher rates of graft rejection/failure and infections over 2 years. These findings represent clinically important safety signals and support multidisciplinary risk-benefit assessment and close graft monitoring when ICIs are considered in kidney transplant recipients. Key outcomes over 2-years after immune checkpoint inhibitor exposure. Outcome ICI (n=113) No ICI (n=113) HR (95% CI) P value Graft rejection/failure 19.5% 9.7% 2.43 (1.17-5.02) 0.01 Opportunistic/viral infections 21.2% 13.3% 2.08 (1.09-3.99) 0.02 Transplant complications 35.4% 30.1% 1.59 (1.00-2.53) 0.05 Acute care utilization 61.1% 48.7% 1.72 (1.20-2.47) <0.01 Dialysis utilization 19.5% 14.2% 1.59 (0.83-3.03) 0.16
Risk prediction models for familial breast cancer: A Cochrane systematic review and meta-analysis.
10545 Background: Women with a family history of breast cancer (BC) have an increased risk of developing the disease. Several BC risk prediction models are used in clinical practice to estimate future BC risk, however, their comparative performance in women with a family history of BC is uncertain. The aim of this study was to systematically identify, describe, and critically appraise BC risk prediction models developed or validated in women with a family history of BC, and to synthesize their performance in predicting BC occurrence in this population. Methods: We searched MEDLINE, Embase, CINAHL, and ISI Web of Science up to February 2022, with a targeted MEDLINE update to 19 December 2024. We included studies that developed or externally validated BC risk prediction models in women with a family history of BC, provided family history was included as a predictor. Data were extracted using the CHARMS checklist, and risk of bias was assessed using PROBAST. Where data from more than three validation studies were available, random-effects meta-analyses of calibration (observed/expected [O/E] ratios) and discrimination (c-statistic) were conducted. Results: Forty-five studies were included. Twelve models were externally validated in the target population; four were validated more than three times and included in meta-analyses. Reporting quality was variable, and most studies had high or unclear risk of bias. The Gail (BCRAT) model was well calibrated (pooled O/E 1.06, 95% CI 0.91–1.25) but showed modest discrimination (c-statistic 0.61, 95% CI 0.57–0.66). BOADICEA was also well calibrated (O/E 0.98, 95% CI 0.90–1.17) with modest discrimination (c-statistic 0.65, 95% CI 0.58–0.71). Tyrer-Cuzick (IBIS) overpredicted risk (O/E 0.86, 95% CI 0.74–0.98), while BRCAPRO underpredicted risk (O/E 1.44, 95% CI 1.25–1.62). Discriminatory accuracy was similar across Tyrer-Cuzick v8, BOADICEA, and BRCAPRO, with pooled c-statistics of 0.64 (0.58 to 0.71), 0.65 (0.58 to 0.71),0.64 (0.54 to 0.73) respectively and slightly higher than Gail (pooled c-statistic 0.61 (0.57 to 0.66)) . Conclusions: In women with a family history of BC, Gail and BOADICEA are well calibrated, while Tyrer-Cuzick overpredicts and BRCAPRO underpredicts risk. No model demonstrated clearly superior discrimination. Considering both calibration and discrimination, BOADICEA may be useful for clinical risk assessment in this population, although conclusions are limited by study heterogeneity, small numbers of validation studies in the target population, and high or unclear risk of bias. Improved model performance and reporting are needed. This abstract is based on a post-peer review version of a Cochrane Review. Upon acceptance, the final version is expected to be published in the Cochrane Database of Systematic Reviews (www.thecochranelibrary.com).
GK01 stemness-enriched tumor-reactive T-cell therapy plus IL-2 in advanced solid tumors: ORR and clonal persistence results in a first-in-human phase I study (GUARDIAN-01).
2540 Background: T-cell exhaustion and poor persistence limit tumor infiltrated lymphocytes (TILs) efficacy in solid tumors. GK01 is an autologous tumor-reactive T-cell product enriched for stem cell memory T cells (TSCM: CD45RA + CD62L + ) and diverse T-cell receptor (TCR) clonotypes to promote durable engraftment. We conducted GUARDIAN-01 (NCT06954558), a phase I study of GK01 plus IL-2 in advanced solid tumors. Methods: This single-arm, open-label study enrolled patients with advanced solid tumors (ECOG PS 0-1; measurable disease per RECIST v1.1). Patients received standard lymphodepletion, GK01 (5×10 9 -1×10 11 cells per manufacturing yield), and IL-2 (300,000 IU/kg IV q12h, up to 5 days). Repeat infusion was permitted at investigator discretion based on clinical benefit. Primary endpoint was safety; secondary endpoints included objective response rate (ORR), disease control rate (DCR), and cellular kinetics via absolute lymphocyte count (ALC) and TCR sequencing. Results: From March 2025 to January 2026, 6 patients were enrolled (median age 53.5 years; median 2 prior lines; tumor types included gastric n = 3, pancreatic n = 1, penile SCC n = 1, and melanoma n = 1). Manufacturing succeeded in all patients; median time from tissue procurement to infusion was 28 days (range 25-39). Infused GK01 exhibited median TSCM frequency of 71% (range 42-92%) and demonstrated robust expansion and stemness properties. Upon tumor challenge, these T cells secreted IFN-γ at a median of 1,632 pg/mL (range, 35 - 4,886). Median dose was 2.8×10 10 cells (range 1.4×10 10 -8.8×10 10 ); 2 patients received repeat infusion. The median total IL-2 dose administered was 4 (range 1-5), with the first dose administered approximately 6 hours after GK01 infusion. No dose-limiting toxicities (DLTs) occurred. G3/4 adverse events were exclusively hematologic (neutropenia, thrombocytopenia, leukopenia, lymphopenia in all patients), attributable to lymphodepletion. Chills, fever, and erythroderma occurred in all patients but G1-2, resolving within 2 weeks. At median follow-up of 169 days (range 80-297), ORR was 66.7% (4/6 PR; 2/6 SD), and DCR was 100%. The median peak ALC reached at 11.3×10 9 /L (range 4.9-22.7) at days 7-9 post-infusion, remained elevated at 3.1×10 9 /L (range 2.0-6.4) at 1 month. Among patients with available peripheral-blood samples (n = 4), product-derived TCR clonotypes comprised 94% of the circulating repertoire at day 7 and 92% at 2 months. Conclusions: In this first-in-human study, GK01 plus IL-2 demonstrated a favorable safety profile with no DLTs and manageable toxicity. The TSCM-enriched product achieved a 67% ORR and 100% DCR, with product-derived clonotypes persisting at > 90% of the T-cell repertoire at 2 months. These findings validate the stemness-enriched T-cell platform and support expansion cohorts in selected solid tumor indications. Clinical trial information: NCT06954558 .
Prostate-specific antigen outcomes of darolutamide and androgen deprivation therapy in patient subgroups by age, comorbidities, and concomitant medications: ARANOTE post hoc analyses.
5103 Background: Darolutamide (DARO) + androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (HR 0.54, 95% CI 0.41–0.71; P<0.0001) vs placebo (PBO) + ADT in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) in the phase 3 ARANOTE (NCT04736199) trial, with a favorable safety profile. Here, we report the impact of age, comorbidities (comorbid), and use of concomitant medications (conmeds) ongoing at baseline on prostate specific antigen (PSA) outcomes in pts treated with DARO or PBO. Methods: Pts were randomized 2:1 to DARO 600 mg orally twice daily or PBO, both with ADT. Pts were grouped by age and number/type of comorbid or conmeds reported at baseline. Descriptive statistics ( post hoc ) summarized baseline demographics, disease characteristics, and PSA outcomes by age, comorbid, and conmed subgroups. Results: Baseline demographics and disease characteristics were generally similar between DARO (n=446) and PBO (n=223) across all subgroups by age (<65, 65–74, or ≥75 years [yrs]), comorbid (<5 or ≥5), and conmeds (<5 or ≥5), respectively. Rates of reaching PSA <0.2 ng/mL at any time were consistently higher with DARO vs PBO across all age (<65 yrs, 62% [n=69/112] vs 21% [n=13/63]; 65–74 yrs, 62% [n=116/187] vs 21% [n=19/89]; ≥75 yrs, 64% [n=81/126] vs 12% [n=7/59]), comorbid (<5, 66% [n=160/244] vs 21% [n=26/122]; ≥5, 66% [n=86/130] vs 14% [n=10/71]), and conmed (<5, 67% [n=115/173] vs 22% [n=21/96]; ≥5, 62% [n=93/151] vs 16% [n=11/71]) subgroups. With DARO, rates of reaching PSA <0.2 ng/mL at any time were consistent among pts with metabolic disorders with or without corresponding conmeds (71% [n=43/61] vs 69% [n=29/42]). The rate of reaching PSA <0.2 ng/ml was slightly lower in patients with cardiovascular disorders who were not receiving corresponding conmeds at baseline (51% [n=22/43]) compared with those receiving corresponding conmeds (64% [n=119/187]). A substantially lower rate of PSA progression was observed with DARO (8% [n=22/266]) vs PBO (33% [n=13/39]) among pts that reached PSA <0.2 ng/mL. Median time to PSA progression among patients that reached PSA <0.2 ng/mL was 421 days (range, 85–702) and 256 days (range, 85–514) for DARO and PBO, respectively. Conclusions: Overall, an efficacy benefit was observed with DARO, irrespective of age, and number of comorbidities or concomitant medications reported at baseline in pts with mHSPC, including those with cardiovascular or metabolic disorders, with or without corresponding conmeds, respectively. These results support the use of DARO in mHSPC, even in pts with older age, substantial comorbidities, and greater use of concomitant medications. Clinical trial information: NCT04736199 .
A multi-institutional, single-arm, phase 2 study of durvalumab plus amrubicin in patients with relapsed extensive-stage small cell lung cancer (Aphrodite trial).
8105 Background: In patients (pts) with sensitive relapsed (SR) and refractory relapsed (RR) small cell lung cancer (SCLC), amrubicin (AMR) is one of the current standard treatments in Japan. However, the overall survival (OS) in RR is particularly poor, with approximately 6-9 months and a 1-year overall survival rate (1yr-OS rate) of 34%, which is not satisfactory. We conducted the phase 2 exploratory proof-of-concept trial based on preclinical results, which showed that the combination of an anti-PD-1 antibody and a topoisomerase II inhibitor had a synergistic effect on cancer cells. This trial was funded by AstraZeneca K.K. Methods: This trial enrolled pts with SR or RR SCLC that recurred after first-line chemo-immunotherapy. They were treated with durvalumab (1,500 mg on day1) and AMR (40 mg/m 2 on days1-3), every three weeks until progression. After assessing the safety of the combination therapy in the lead-in cohort, we initiated the phase 2 part of the trial. The primary endpoint was the 1yr-OS rate calculated based on a year consisting of 48 weeks. The secondary endpoints consisted of OS, progression-free survival (PFS), overall response rate (ORR) etc. The expected 1yr-OS rate for SR and RR were 61.1% and 44.4%, respectively, which were 10% higher than the systematic review result for AMR alone in Japanese pts. Based on this review result and considering feasibility, the sample size was planned as 18 pts for each SR and RR. Results: Between July 2022 and August 2024, a total of 23 (SR: 5; RR: 18) pts were enrolled. All pts had previously received treatment with platinum-containing drugs and immune checkpoint inhibitors (ICI). The SR group could not be enrolled till sufficient sample size for statistical analysis. The 1yr-OS rate was 80.0% for SR group, which included a complete responder. The efficacy results for the RR group were: The 1yr-OS rate was 44.4% (95% confidence interval (CI): 21.6-65.1). The median PFS and OS were 15.1 weeks (95% CI: 11.0-23.3) and 43.1 weeks (95% CI: 24.6-64.3), respectively. The ORR was 38.9% (95% CI: 17.3-64.3). Grade 3 or higher adverse events were observed in 65.2% of all 23 pts, but no new events beyond those previously reported were identified. The most frequent Grade 3 or higher adverse event was neutropenia (43.5%), with febrile neutropenia occurring in 13.0%. Grade 3 or higher pneumonia was observed in 4.3%, and no treatment-related deaths were reported. Conclusions: The combination therapy of durvalumab and AMR suggests favorable efficacy and tolerable safety, particularly in pts with RR, even in those who had already received ICI treatment. Clinical trial information: jRCT2061220036.
First-in-human phase 1 study of TQB6411, an EGFR/c-Met bispecific antibody-drug conjugate (ADC), in patients with advanced solid tumors.
3032 Background: EGFR and c-Met overexpression are common across various solid tumors. TQB6411 is a novel ADC binding to both EGFR and c-Met with a valency of 1:2 to enhance the affinity to c-Met. Here we report the preliminary results of this first-in-human phase 1 study of TQB6411(NCT07043751). Methods: Patients (pts) with advanced malignant tumor who had failed or were intolerant to standard treatment were eligible. TQB6411 was administered intravenously once every 3 weeks. An accelerated titration design was used for the initial dose level (0.8 mg/kg), followed by a conventional 3+3 dose escalation design for the remaining dose levels. The primary endpoints were dose-limiting toxicity (DLT), recommended phase II dose and safety. Results: As of December 31, 2025, 26 pts were enrolled and received research treatment (median age [range], 60[33–75] years; 46.2% female). The most common diagnosis was non-small cell lung cancer (NSCLC, 21 pts), followed by esophageal cancer (EC, 3 pts) and colorectal cancer (CC, 2 pts). All pts had received at least one previous line of systemic treatment. Dose group assignments were as follows: 1 in 0.8mg/kg, 3 in 2.4mg/kg, 13 in 4mg/kg, 6 in 5.3mg/kg, and 3 in 6.6mg/kg. By the data cutoff date of January 9, 2026, the dose had been escalated to 6.6mg/kg, with no DLT occurring. The median treatment duration was 3 cycles (rang:1-9). In 22 pts who were followed up for at least 21 days, 19 (86.4%) experienced at least 1 treatment-related adverse event (TRAE). The most common TRAEs included asthenia (54.5%), infusion reaction (50.0%, decreasing to 38.9% in the ≥4 mg/kg dose group after prophylaxis modification), myalgia (27.3%), alopecia (22.7%), and neutrophil count decreased (22.7%). No interstitial lung disease occurred. Only 4 cases of grade 3 AEs (two of neutrophil count decreased, one of allergic shock, one of white blood cell count decreased) were observed in 3 pts and were all attributed to TQB6411. No ≥ grade 4 AEs occurred. In the ≥4 mg/kg dose group, 8 pts received at least one imaging assessment, 4 achieved a partial response (PR), giving an objective response rate of 50.0%. The disease control rate was 100%. The details of efficacy results are shown in the table below. Conclusions: In this ongoing phase 1 study. TQB6411 showed an impressive safety profile, with a lower incidence of higher-grade TRAEs (especially lower haematological toxicities), and encouraging efficacy, with tumor responses could be observed even in the relatively lower dose group. Clinical trial information: NCT07043751 . 4mg/kg (N = 6) 5.3mg/kg (N=2) PR, n 3 (NSCLC: 2, EC:1) 1(NSCLC) SD, n 3 (NSCLC) 1 (NSCLC)
Impact of lymph node dissection extent on disease-free survival with postoperative nivolumab plus concurrent chemoradiotherapy in head and neck squamous cell carcinoma: A post-hoc analysis of the NIVOPOSTOP trial.
6001 Background: Postoperative nivolumab added to concurrent Chemo-Radiotherapy (CRT) after surgery has been shown to improve disease-free survival (DFS) in patients with resected head and neck squamous cell carcinoma (HNSCC) at high risk of relapse. However, extensive nodal dissection has long be suspected to hinder response to immunotherapy but prospective data remains scarce. Methods: We analyzed the surgical procedures of the patients included in the primary analysis of the NIVOPOSTOP study regarding neck lymph node dissection (LND). Patients were classified with either uni- or bilateral LND. The number of nodes in the pathological report was also studied. The extent of the LND on DFS was analyzed in univariate and multivariate analysis. Results: Surgical information was available for all 666 patients. Four patients did not undergo any LND. Of the 662 patients who underwent nodal surgery, 239 (36%) underwent unilateral LND and 423 (64%) bilateral LND. The proportion of patients with bilateral / unilateral LND was similar in both treatment. Patients who underwent bilateral LND had statistically higher stage tumors versus unilateral LND (76% vs 61% stage IV) and a significantly higher proportion of laryngeal and hypopharyngeal tumors (17% vs 3% and 16% vs 7% respectively). The median numbers of nodes removed were 39 overall, 25 on the right side of the neck, and 24 on the left. As compared to unilateral LND, bilateral LND was associated with worse DFS in univariate analysis (HR 1.56 (95%CI 1.18; 2.05)). After adjusting for performance status, tumor site and p16 status, clinical stage, pathological risk factors of relapse (nodal extracapsular extension, margin status, perineural invasion, ≥ 4 involved nodes), the association was no longer statistically significant: HR 1.26 (95%CI 0.92; 1.71), Wald test p-value 0.15. There was no interaction between the type of LND (unilateral or bilateral) and the type of treatment (without or with nivolumab) on DFS. The benefit of adding Nivolumab to CRT was similar for unilateral LND (HR 0.79 (95%CI 0.50; 1.26)) and bilateral LND (HR 0.77 (95%CI 0.57; 1.03)) in Cox model stratified for p16 status. Regarding the extent of LND, the benefit of adding Nivolumab to CRT in the 330 patients who underwent removal of more than 39 neck lymph nodes, on one or both sides, was similar to that of the whole population (HR 0.75 (95%CI 0.54; 1.05)). Conclusions: The DFS benefit of adding nivolumab to standard postoperative therapy (cisplatin-RT) was not changed by whether the LND was bilateral or unilateral and persisted in patients in whom more than 39 cervical lymph nodes were removed, on one or both sides. As such, no evidence supports reducing the extent of neck LND when immunotherapy is incorporated into the management of high risk resected HNSCC. Clinical trial information: NCT03576417 .
Association of asynchronous, time-flexible digital multidisciplinary care with overall survival in advanced biliary tract cancer treated with immune checkpoint inhibitors.
4116 Background: Delayed recognition and fragmented management of immune-related adverse events (irAEs) can trigger unnecessary interruption/discontinuation of immune checkpoint inhibitors (ICIs) and compromise real-world outcomes. We built an asynchronous, message-based multidisciplinary care system embedded in a widely used instant messaging platform to support longitudinal management for advanced biliary tract cancer (BTC) on ICIs, and assessed outcome changes from exploratory to protocolized implementation beyond secular trends. Methods: Single-center retrospective cohort of 546 adults with unresectable locally advanced/metastatic BTC receiving ≥1 ICI dose (Jan 2019–Jan 2024). All patients entered a clinician-moderated closed digital care group with structured triage and multidisciplinary coordination. By ICI start date: WGMS-E (before Jan 1, 2021) vs WGMS-P (on/after Jan 1, 2021). Primary endpoint: overall survival (OS). Secondary: progression-free survival (PFS), irAE recognition/management, and ICI rechallenge. Inverse probability of treatment weighting (IPTW) balanced baseline covariates. Interrupted time-series (ITS) analysis disentangled intervention effect from secular improvements in care. Results: Median follow-up 29.1 months; median OS overall 15.0 months. OS improved in WGMS-P vs WGMS-E (21.3 vs 12.4 months; log-rank P < 0.0001). IPTW-weighted Cox: WGMS-P associated with lower mortality (HR 0.55; 95% CI 0.43–0.69; P < 0.001) and higher 1-/2-year survival (~18%/~19% absolute). PFS also favored WGMS-P (HR 0.72; 95% CI 0.59–0.89; P = 0.0019). Overall irAE incidence was similar, but first irAE recognition occurred earlier in WGMS-P (restricted mean difference −1.68 months within 12 months). Permanent ICI discontinuation due to irAEs decreased (11% vs 22%), while rechallenge increased (10% vs 4%) without higher recurrent irAEs. ITS showed reversal of an increasing pre-intervention mortality trend to a decreasing post-intervention trend. Conclusions: A protocolized, asynchronous, message-based multidisciplinary care system integrated into routine oncology workflows was associated with improved survival among patients with advanced BTC treated with ICIs. By enabling earlier irAE recognition, reducing unnecessary permanent discontinuation, and facilitating safer rechallenge, this low-cost digital intervention may represent a scalable strategy to optimize real-world immunotherapy outcomes beyond secular advances in cancer care. These findings suggest that small, low-cost organizational changes in care delivery may translate into disproportionately large survival gains.
Immune-related adverse events with immune checkpoint inhibitors: Insights from real-world practice in Brazil.
e23338 Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of multiple malignancies and are associated with a broad spectrum of immune-related adverse events (irAEs). Early recognition and appropriate intervention are critical for effective irAE management and to reduce treatment discontinuation in routine clinical practice. However, real-world data describing the incidence and patterns of irAEs remain limited. Methods: We conducted a retrospective, descriptive, single-center study using electronic medical records at a tertiary oncology center in São Paulo, SP, Brazil, to characterize patients treated with ICIs who developed irAEs between January 1, 2018, and December 31, 2025. Adult patients with histologically confirmed solid tumors who received at least one dose of an ICI, either as monotherapy or in combination (with another ICI and/or chemotherapy), were included. Patients with pre-existing autoimmune disease requiring immunosuppressive therapy, or receiving chronic systemic corticosteroids or other immunosuppressants at baseline for any indication, were excluded. irAEs were identified from clinical documentation and graded according to CTCAE v5.0. Descriptive statistics were used: categorical variables were summarized as counts and percentages, and continuous variables were summarized as median (interquartile range). Results: A total of 236 patients were included. The median age was 63 years (IQR 47–75), and 57.2% were female. Most patients received ICIs in the palliative setting (80.5%) and had good performance status, with ECOG 0-1 in 89.8%. Melanoma was the most frequent primary tumor (27.9%), followed by lung cancer (26.7%). Pembrolizumab was the most frequently used ICI (44.5%). Adverse events of any grade occurred in 54.2% of patients, of which 40.7% were immune-related. Among patients with immune-related adverse events, the most frequent categories were endocrine toxicities (26.0%) and cutaneous toxicities (22.9%). The median cycle at irAE onset was 3 (IQR 2–7). Grade 3-4 adverse events were observed in 12.7% of patients. Overall, systemic corticosteroids were required in 18.6% of patients, and treatment interruption or discontinuation due to toxicity occurred in 18.2% of patients. Conclusions: In this real-world single-center cohort, irAEs associated with ICIs were common and clinically relevant, frequently requiring systemic corticosteroids and leading to treatment interruption or discontinuation in a substantial proportion of patients. These findings emphasize the importance of early recognition and structured management of irAEs in routine oncology practice.
Deciphering the intricate crosstalk of the EFNA1-EPHA3 axis in orchestrating the proangiogenic niche of cervical adenocarcinoma: A promising therapy target.
e17508 Background: Cervical adenocarcinoma (ADC) shows more malignant phenotypes and poorer prognosis compared to squamous cell carcinoma (SCC). Anti-angiogenesis therapy is a promising therapeutic strategy for cervical cancer, yet it is not as efficient in ADC as that in SCC. Therefore, a better understanding of ADC angiogenesis is needed to develop precise anti-angiogenic therapies. Methods: A 120 patients clinical cohort of 24 ADC patients and 96 SCC patients were included. Single-cell RNA sequencing was performed on 42 samples (12 ADC and 21 SCC). Integrated 3D angiogenesis study system in vitro including vascularized ADC-derived tumoroids and tumoroids-on-a-chip and in vivo xenograft were established to explore the anti-angiogenic effect of targeting the EFNA1-EPHA3 axis by ifabotuzumab. Results: ADC patients displayed more aggressive clinical features (higher vaginal involvement, parametrial infiltration, uterine involvement, lymph node metastasis, adnexal involvement and recurrence incidence). Importantly, a higher incidence of lymphovascular space invasion (LVSI) in patients with ADC, suggesting ADC patients were more prone to angiogenesis compared with SCC patients. ADC epithelial cells and ADC-associated fibroblasts wrapped around tumour microvessels via the EFNA1-EPHA3 axis, forming a unique structure "proangiogenic niche". Based on the ADC-derived tumoroids we established, we constructed 3D vascular-like system integrated ADC-derived tumoroids and microfluidics-based tumoroids-on-a-chip, which successfully recapitulated the proangiogenic niche supported by the EFNA1-EPHA3 axis within ADC. For preclinical exploration, we validated the antiangiogenic effect of targeting the EFNA1-EPHA3 axis using ifabotuzumab based on in vitro vascular-like system integrated 3D ADC-derived tumoroid model, microfluidics-based tumoroids-on-a-chip and an in vivo xenograft model, highlighting the potential of ifabotuzumab in preclinical antiangiogenic therapy for ADCs. Conclusions: Our study inventively proposed "proangiogenic niche" connected by EFNA1-EPHA3 axis and highlighted ifabotuzumab as a promising anti-angiogenesis therapy for ADCs. Besides, we originally constructed integrated 3D angiogenesis study system.
Evaluation of fine-tuned small language models (SLMs) vs large language models (LLMs) in modeled patient conversations for lung cancer screening.
e24116 Background: Lung Cancer Screening (LCS) uptake in the US remains suboptimal at approximately 18%, with disproportionately lower rates among those with limited health literacy. While Generative AI offers a scalable solution to improve patient access to information, uninstructed commercial large language models (LLMs) exhibit language complexity that limits their utility as equitable decision-support tools. Building on our prior work demonstrating their limitations, we aimed to develop a deployable, patient-centric, small language model (SLM) to address this accessibility gap. Methods: We fine-tuned two SLMs (Google: Gemma-7B and MedGemma-4B) using Parameter-Efficient Fine-Tuning (PEFT/LoRA) on a curated dataset of physician-scored, empathetic dialogues. We modelled conversations using five patient personas (e.g. anxious, low health-literacy) to compare fine-tuned SLMs against uninstructed LLMs (GPT-4o, Gemini Pro 2.5), with static patient information (FAQs). Endpoints included readability (Flesch-Kincaid Grade Level [FKGL]), empathy (reduction in "fear-inducing" sentiment via RoBERTa analysis), clinical safety (semantic adherence to national patient information guidance via BERTScore) and technical density (Type-Token Ratio). Results: Uninstructed LLMs produced responses with a mean reading difficulty of Grade 11.8 (SD 1.7), exceeding the recommended 6th-8th grade level for patient materials. In contrast, the fine-tuned Gemma-7B SLM achieved a mean Grade Level of 6.6 (SD 2.2), making it significantly more accessible than both the generalist models ( P < .001) and static patient information ( P < .001). Regarding empathy, the 7B model reduced the frequency of fear-inducing language by 44% compared to the LLMs (12.1% vs 21.6%; P < .05). Crucially, this simplification did not compromise safety; the 7B model demonstrated high semantic adherence to official patient guidance (BERTScore 0.95) and was non-inferior to public FAQs ( P > 0.05). The smaller MedGemma-4B, however, exhibited a trade-off: while highly accurate, it prioritised technical density (Type-Token Ratio 0.97) over readability (Grade 14.8; P < .001 vs 7B), rendering it less suitable for direct patient interaction. Conclusions: Building on our prior demonstration of an equity blindspot with uninstructed commercial LLMs, this study suggests that a fine-tuned 7B-parameter SLM may decouple clinical accuracy from linguistic complexity in the context of LCS patient information. We demonstrate that SLMs offer a safe, deployable, and resource-efficient alternative that maintains high fidelity to national guidelines while remaining accessible to low-literacy populations. Future work will focus on validating these findings in real-world patient cohorts to assess impact on screening uptake.
A retrospective analysis examining liquid biopsies with tissue biopsies in patients with advanced non–small cell lung cancer.
e20683 Background: Non-small cell lung cancer (NSCLC) is genetically diverse, often harboring actionable mutations (AM) that can be targeted. It is critical that providers accurately and quickly identify AM through next-generation sequencing (NGS). Tissue-based biopsies (Tbx) are invasive and have long turnaround times. Blood-based biopsy (Bbx), a less invasive and faster technique, analyzes circulating tumor DNA from blood samples. Our first aim is to report TBx and Bbx concordance rates stratified based on different AM. Our second aim is to report the lead time provided by Bbx compared to Tbx in starting treatment. Methods: This single-institution, retrospective, IRB-approved study analyzed patients treated between January 1, 2016 and December 31, 2025. Only patients whose charts were complete and contained both a Tbx and a Bbx obtained within 30 days of one another at the time of initial diagnosis were included. We included only cases with fully scanned NGS reports available in the electronic medical record—not summaries, interpretations, or partial documentation. Results: 66 patients were analyzed. Median age was 69 years, with 41% male and 59% female. Ethnicities include Asian (26%), African American (9%), Hispanic (3%), and Caucasian (51%). 51% reported current or prior tobacco use. 68% had a tissue biopsy followed by liquid biopsy. 67% had an AM finding on Bbx with predominant reason for ‘negative result’ being ‘ctDNA not detected”; while 55% had an AM finding on Tbx, with most common reason for ‘negative result’ being insufficient tissue. 24% of patients had an AM solely present on Bbx while 9% of patients had an AM solely present on Tbx. Concordance rates between Tbx and Bbx were stratified based on mutations: EGFR exon 19 (95%)(84.9% - 98.7%), EGFR exon 21 (95%)(84.9% - 98.7%), ALK (95%) (84.9% - 98.7%), ROS (98%) (89.7% - 99.9%), MET (92%)(80.6% - 96.8%), BRAF (90%)(78.5% - 95.8%). Time to report for treatment for AM based on Bbx was a median of 8 days while Tbx was 30 days. Amongst the patients with AM finding on Bbx, 39% were started on targeted treatments based on BBx results prior to availability of results from Tbx with a median lead time of 13.5 days. Conclusions: Our study adds valuable real-world data to the existing literature. While concordance between the two modalities is extremely high for all types of AM, our data also shows that mutations can be solely picked up on Bbx but not on Tbx and vice versa. This finding supports the complementary use of both Tbx and Bbx at initial diagnosis as necessary for thoracic oncologists. Discordance in mutation detection by Bbx and Tbx can be due to tumor heterogeneity, sensitivity of the assays, as well as RNA quality and quantity. Since our cohort spanned nearly a decade, discordance could also have been influenced by the evolution of NGS assays and tech. Our data also showcases the lead-time advantage with Bbx, enabling early initiation of treatment.
A double-blind, double-dummy, randomized, controlled phase 3 trial of iparomlimab and tuvonralimab (QL1706) vs QL1604 as consolidation therapy following concurrent or sequential chemoradiotherapy (cCRT/sCRT) in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC).
TPS8133 Background: LS-SCLC is a highly aggressive malignancy with poor prognosis. Positioning effective consolidation strategies is a key focus to improve long-term patient outcomes. Prominently, immune checkpoint inhibitors (ICIs) have emerged as consolidation therapy after cCRT or sCRT for LS-SCLC. QL1706 is a bifunctional antibody against both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4, and iparomlimab (QL1604) is an anti-PD-1 agent. In previous studies, both QL1706 and QL1604 demonstrated manageable safety profiles. Notably, QL1706 also showed encouraging preliminary anti-tumor signals in SCLC, which indicated the potential as consolidation therapy (Zhao et al. 2023; Huang et al. 2023). This trial aims to compare the efficacy and safety of QL1706 and QL1604 as consolidation therapy in pts with LS-SCLC without progression after cCRT or sCRT. Methods: In this multicenter double-blind double-dummy randomized controlled phase 3 trial (NCT06789796), pts with pathologically-confirmed LS-SCLC per AJCC 8 th edition are recruited. Pts are eligible if aged ≥18 years, with adequate organ function, ECOG PS scored 0 or 1, and do not have disease progression after completion of the requested cCRT or sCRT. Prophylactic cranial irradiation (PCI) is permitted before randomization. Approximately 636 pts are planned to be randomized 1:1 to receive either QL1706 (at 5 mg/kg) plus QL1604 placebo or QL1604 (at a fixed dose of 200 mg or at 3 mg/kg for pts weighing <40 kg) plus QL1706 placebo via intravenous infusion on day 1 in a 21-day cycle. Treatment will be continued until disease progression, intolerable toxicity, initiation of new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, trial termination, or up to 24 months, whichever occurs first. Randomization is stratified by disease stage (I/II vs. III), receipt of PCI (yes vs. no), and the type of CRT (cCRT vs. sCRT). The co-primary endpoints are progression-free survival (PFS) per RECIST v1.1 assessed by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints are investigator-assessed PFS, 1-year and 2-year PFS rates assessed by BICR and investigator, objective response rate, disease control rate, duration of response, 1-year and 2-year OS rates, safety, pharmacokinetics, and immunogenicity. Exploratory endpoints are biomarker assessments and their relationship to efficacy and prognosis, as well as patient-reported outcomes. Overall two-sided Type I error (α=0.05) controlled by fixed-sequence testing: BICR assessed PFS will be tested first, followed by OS if significant. An interim analysis is planned. The study will be conducted across around 79 sites in China, and enrollment is ongoing. Clinical trial information: NCT06789796 .
Petra Utroša
A Chiral Multifunctional Phosphine Ligand for Gold‐Catalyzed Diastereo‐ and Enantioselective Cyclization of Yne‐enones/Enol‐Addition
ABSTRACT The Au(I)‐catalyzed asymmetric cascade cyclization of yne‐enones/addition represents a powerful strategy for constructing furan skeletons; however, the use of enol‐type carbon nucleophiles in this transformation remains a considerable challenge. In this study, we report the development of a novel bio‐inspired chiral multifunctional phosphine ligand and its application in Au(I)‐catalyzed highly diastereo‐ and enantioselective cyclization of yne‐enones/enol‐addition. The catalytic system tolerated a broad range of substrates, for the first time, providing access to furan products bearing consecutive stereocenters via this reaction type. Control experiments and DFT calculations underscore the validity of our cooperative multifunctional design, wherein modular multiple chiral centers and tailored noncovalent interactions collectively account for the excellent stereocontrol and high chemoselectivity observed.