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A phase 1, first-in-human (FIH) study evaluating the safety, pharmacokinetics, and efficacy of ABBV-969 in patients with metastatic castration-resistant prostate cancer (mCRPC).
5014 Background: Prostate-specific membrane antigen (PSMA) and six-transmembrane epithelial antigen of prostate 1 (STEAP1) are overexpressed in >80% of metastatic prostate cancer tumors. ABBV-969 is a first-in-class PSMA/STEAP1 dual-targeting antibody drug conjugate with a topoisomerase 1 inhibitor (Top1i) payload. We report results from the completed dose escalation part of the phase 1, FIH study (NCT06318273) evaluating ABBV-969 in patients (pts) with mCRPC. Methods: Pts were ≥18 years with confirmed metastatic prostate adenocarcinoma, had an ECOG performance score ≤1, a serum prostate-specific antigen (PSA) level ≥1.0 ng/mL, and hemoglobin ≥9 g/dL at study entry. Pts received ≥1 novel hormone agent (NHA) and ≥1 taxane (unless unable to receive or declined taxane), and progressed on prior NHA. Pts received 1 mg/kg–12.5 mg/kg of ABBV-969 monotherapy every 3 weeks until disease progression or intolerable toxicity. Primary objective was to determine safety and tolerability. Secondary objectives were preliminary efficacy, pharmacokinetics, and recommended phase 2 dose. Results: As of Jan 2026, 49 pts with mCRPC received ABBV-969 in the dose escalation part of the study. Median follow-up was 11.1 months (95% CI, 8.4–13.2), and median number of prior lines was 5 (range 1–9). Pt demographics and safety results are shown in Table 1. Thirty-one (63%) pts had Grade (G) ≥3 TEAEs, primarily G3 anemia (n=24). Dose and exposure responses were observed, with durable PSA and objective responses noted at all dose levels ≥3 mg/kg. At dose levels ≥3 mg/kg, confirmed PSA50 and PSA90 responses were 67% (95% CI, 52–81) and 28% (95% CI, 15–44), respectively. Among 29 pts with RECIST-evaluable disease, the confirmed ORR, as assessed by investigator, was 45% (95% CI, 26–64). At data cut, 26 pts were receiving ongoing treatment. Radiographic PFS will be presented. Conclusions: ABBV-969 demonstrated promising antitumor activity and a manageable safety profile in heavily pretreated pts with mCRPC. Dose optimization is ongoing. Clinical trial information: NCT06318273 . Pt demographics and safety. TotalN=49 Median age, years (range) 71 (57–84) Median PSA, µg/L (range) 74 (2–2879) Disease location, n (%)BoneLymph nodeLiverLungAdrenal gland 43 (88)20 (41)8 (16)7 (14)2 (4) Prior therapy, n (%) a Androgen-receptor pathway inhibitorDocetaxelCabazitaxel 177 Lu-PSMA-617 49 (100)41 (84)19 (39)23 (47) Any Grade TEAE of interest, n (%)Hematologic toxicityGastrointestinal toxicitySalivary gland toxicity 38 (78)33 (67)6 (12) TEAE leading to, n (%)Discontinuation b InterruptionReduction 3 (6)24 (49)16 (33) TEAE leading to death, n (%) c Pneumonitis c 1 (2)1 (2) DLT events, n (%) d 3 (6) a Only therapies of interest listed. b G3 pneumonitis and disease progression. c ABBV-969-related. d Anemia at ≥8 mg/kg doses. DLT, dose-limiting toxicity.
Prevalence and factors associated with chemotherapy-induced anemia in early and locally advanced breast cancer: A prospective tertiary care center study from India.
e12688 Background: Chemotherapy-induced anemia (CIA) affects up to 89% of non-anemic cancer patients undergoing chemotherapy. CIA significantly impacts treatment outcomes and quality of life. This prospective study investigated the prevalence, associated factors, and quality-of-life implications of CIA in early and locally advanced breast cancer patients undergoing neoadjuvant or adjuvant chemotherapy. Methods: A prospective study enrolled 200 eligible patients with Stage I–III breast cancer receiving chemotherapy at a tertiary cancer center in Kerala (September 2023–June 2025). A baseline hemoglobin level of ≥12 g/dL was required. Patients were monitored pre-chemotherapy for the development of anemia and classified according to WHO criteria. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool. Results: All 200 patients (100% female, median age 56 years) developed CIA. Anemia severity distribution: mild 36.5% (n=73), moderate 48.5% (n=97), severe 15% (n=30). Statistically significant factors associated with severe anemia included younger age ≤ 50 years (p=0.004), premenopausal status (p=0.005), dose-dense chemotherapy (p<0.001, OR=6.60), and neoadjuvant treatment sequence (p=0.001, OR=4.13). Quality-of-life scores decreased significantly with increasing anemia severity across all FACT-An domains (p<0.001). Post-treatment quality of life improved substantially in severe CIA patients. Conclusions: This study establishes CIA as a universal hematologic toxicity warranting proactive surveillance and early intervention protocols in breast cancer populations, particularly in younger patients receiving intensive chemotherapy. Integration of CIA assessment into routine supportive care monitoring represents an actionable quality improvement opportunity to optimize treatment tolerance, preserve functional capacity, and enhance patient-reported outcomes throughout the cancer trajectory. Prevalence and risk factors associated with severe chemotherapy-induced anemia. Anemia Severity Number (n) Percentage (%) Risk Factors Odds Ratio 95% CI P Value Mild (Grade 1) 73 36.5 Age >50 years 0.31 0.14–0.68 0.004 Moderate (Grade 2) 97 48.5 Postmenopausal status 0.32 0.14–0.70 0.005 Severe (Grade 3) 30 15.0 Dose-dense regimen 6.60 2.75–15.82 <0.001 Neoadjuvant chemotherapy 4.13 1.74–9.80 0.001
Comprehensive molecular profiling of salivary gland cancers: A single-institution experience.
e18136 Background: Standardized therapeutic strategies are currently lacking for salivary gland cancers (SGCs). Molecular profiling may improve diagnostic and prognostic accuracy, and support personalized treatment. Methods: Between August 2022 and December 2025, 115 patients with SGCs were managed at the Veneto Institute of Oncology, Padua. Molecular profiling was only performed in recurrent/metastatic (R/M) patients with unknown actionable targets or those who had not previously responded to targeted therapy. Comprehensive genomic profiling was performed using the TruSight Oncology 500 panel. The aim was to evaluate the spectrum of genomic alterations and to identify predictive or prognostic biomarkers to guide personalized therapy. Molecular findings were reviewed by the Veneto Regional Molecular Tumor Board. A tumor mutational burden (TMB) ≥10 mutations/Mb was considered a potentially actionable biomarker. Results: A total of 28 patients with R/M SGCs were retrospectively analyzed. The most common primary site was the parotid gland (15 patients), followed by the submandibular gland (7 patients) and minor salivary glands (6 patients). Test failures occurred in 5 cases. Among the 23 profiled patients, ductal carcinoma was the most frequent histotype (10 patients), followed by adenoid cystic carcinoma (ACC; 9). Other non-ACC cases included two adenocarcinomas NOS, one mucoepidermoid carcinoma, and one epithelial-myoepithelial carcinoma. Overall, 76 pathogenetic/likely pathogenetic alterations were identified: 70 DNA mutations (92%) and 6 RNA fusions (8%). High TMB (TMB-H) was detected in 2 patients (9%). Nineteen actionable targets according to the ESCAT definition were identified in 14 patients (61.%). Five patients harbored more than one actionable alteration. Most therapeutic targets were found in non-ACC histotypes (Table1). Personalized treatment was administered to 7 patients (50 %) through compassionate-use, off-label programmes, or clinical trials, achieving an objective response rate (ORR) of 45%. Seven patients with actionable mutations did not receive targeted therapy due to drug unavailability or clinical decisions. Conclusions: SGCs remain a therapeutic challenge due to their biological heterogeneity and limited treatment options. Comprehensive molecular profiling is a valuable tool for characterizing the genomic landscape and identifying potential therapeutic targets, particularly in non-ACC histotypes. Actionable alterations n (%) Non-ACCn.14 ACCn.9 NTRK fusions 1 (7%) 0 PIK3CA mutations/amplification 3 (21%) 0 H-RAS mutation 4 (29%) 0 NOTCH1 0 1 (11%) BRAF V600E 3 (21%) 0 ALK/ROS1 fusion 1 (7%) 0 Her2 amplification/mutation 2 (14%) 0 HRD-like profile* 1 (7%) 0 TMB-H 1 (7%) 1 (11%) dMMR 1 (7%) 0 *HRD-like: presence of genomic alterations suggestive of homologous recombination deficiency.
Trends in eligibility criteria in solid tumor systemic therapy trials over time.
e23018 Background: Friends of Cancer Research (FRIENDS) advocates for the broadening of eligibility criteria to ensure clinical trials are representative of real-world populations. Whether these recommendations have resulted in measurable changes in eligibility criteria over time remains unclear. We compared eligibility criteria in systemic therapy clinical trials for solid tumours conducted over a 10-year period. Methods: We identified randomized phase 2 and 3 clinical trial protocols evaluating systemic therapies for solid tumours published in 2012-2013 and 2022-2023 in the New England Journal of Medicine, Lancet, and Lancet Oncology. We focused on extraction of eligibility criteria on key recommendations from FRIENDS including HIV status, brain metastases, and organ dysfunction (e.g., myocardial infarction history). We compared eligibility criteria across the time points using Chi-square tests for categorical variables and Mann Whitney U tests for skewed continuous data. Results: We included 42 and 98 protocols from 2012-13 and 2022-23, respectively. Most protocols were phase III trials. Older protocols predominantly focused on breast, gastrointestinal, and skin cancers (33.3%; 11.9%; 14.3%), whereas more recent protocols more commonly evaluated gastrointestinal, genitourinary, and lung cancers (25.5%; 18.4%; 18.4%). Although targeted therapies were consistently examined across time, protocols shifted from a chemotherapy-dominant focus toward immunotherapy. Over time, there was a significant reduction in the proportion of studies excluding patients with brain metastases (71.4% in 2012-13 vs 33.0% in 2022-23). A higher proportion of 2022-23 protocols included patients with a history of myocardial infarction compared with 2012-23 protocols (26.2% vs 38.8%; p = 0.0001). Conversely, a higher proportion of recent protocols excluded patients with positive HIV status compared with older protocols (2012-13: not mentioned 64.3%; excluded 35.7%; 2022-23: not mentioned 21.4%; included with caveat 9.2%; excluded 69.4%). Conclusions: We observed significant differences in eligibility criteria over time. The increased inclusion of patients with brain metastases is encouraging; however, in other areas such as HIV status, ongoing work is needed to broaden criteria and ensure that trial populations are reflective of the real-world populations in which the drugs are likely to be used. These exclusions may compromise external validity and equity, highlighting the need for closer alignment with regulatory recommendations.
Potential cancer susceptibility genes in metastatic lung cancer: A Hong Kong territory–wide genomic study.
e22646 Background: Cancer susceptibility genes (CSGs) are increasingly identified in lung cancer with the widespread adoption of comprehensive genomic profiling (CGP). However, the prevalence of putative CSG variants detected through tumor only sequencing and their associations with molecular and clinical features in Asian patients with metastatic lung cancer remain poorly defined. Methods: This territory wide prospective cohort study included patients with metastatic lung cancer who underwent tumor only comprehensive genomic profiling using FoundationOne CDx as part of the Hong Kong Territory Wide Lung Cancer Genomics Project. Patients reported to harbor putative CSG variants were identified. Clinical characteristics, including age at diagnosis, sex, family history, as well as molecular features including common actionable alterations and PD L1 expression, were compared between patients with and without putative CSG variants. Results: Among 1,324 patients analyzed, 50 patients (3.8%) were reported to harbor putative CSG variants. The most frequent alteration was the MUTYH splice site mutation c.892 2A > G (44% among patients with CSGs), followed by ATM alterations (16%). Alterations in BRCA2 and RAD51D were each observed in 6%, BRCA1 and RAD51C in 4%, and CHEK2, BRIP1, MLH1, TSH2, RET, SDHA, and VHL in 2% each.Median age at diagnosis was similar between patients with and without putative CSG variants (65 vs 66 years, NS), with slight male predominance (74% vs 66%, NS). The overall frequency of family history of cancer was comparable (40% vs 41.6%, NS); however, a numerically higher proportion of patients with putative CSG variants had a family history of lung cancer (16% vs 12.6%, p = 0.21, NS).Patients with putative CSG variants demonstrated a higher proportion of PD L1 positivity (50% vs 37%, p = 0.06) and MET alterations (6% vs 1%, p = 0.0004). The prevalence of EGFR mutations was also higher (44% vs 35%, p = 0.012), while frequencies of ALK (2% vs 1.7%, NS), ROS1 (2% vs 1.5%, NS), and BRAF (2% vs 0.7%, NS) alterations were comparable. Among patients carrying MUTYH mutations, 64% harbored concurrent EGFR mutations, the majority of which were common EGFR variants of exon 19 deletion and L858R mutations (95%). Conclusions: Putative cancer susceptibility gene variants are infrequently identified through tumor only CGP in metastatic lung cancer but are associated with distinct molecular features, including higher rates of EGFR and MET alterations and increased PD L1 expression. While CGP inform therapeutic decision making, it also potentially facilitate prompt referral for genetic counseling on hereditability.
Adjuvant or rescue disitamab vedotin for high-risk non–muscle invasive bladder cancer with HER2 overexpression: A phase II multi-center study.
4616 Background: Disitamab vedotin (DV), a HER2-targeted antibody–drug conjugate (ADC), has shown efficacy in metastatic urothelial carcinoma. However, its role in high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients with HER2 overexpression remains unexplored. We report preliminary findings from an ongoing phase II trial evaluating DV as adjuvant or rescue therapy in this population. Methods: Two cohorts were enrolled: patients receiving adjuvant therapy following transurethral resection (cohort A) and those undergoing rescue therapy after BCG failure (cohort B). Eligible patients had HR-NMIBC with HER2 overexpression. DV was administered at 120 mg intravenously every 2 weeks for up to 10 cycles. The primary endpoints were safety, 12-month recurrence-free survival (RFS) in cohort A, and 3-month clinical complete response (cCR) rate in cohort B. Secondary endpoints included 6-month RFS (cohort A) and duration of response (DOR, cohort B). Exploratory analyses evaluated the prognostic value of urinary tumor DNA (utDNA) using samples collected at baseline, end of treatment, and at the time of disease recurrence. This study is registered with ClinicalTrials.gov (NCT05996952). Results: Between September 2023 and October 2025, 28 patients were enrolled—22 in cohort A (median age 62 years [range, 33–75]; 3 women [13.6%]) and 6 in cohort B (median age 66 years [range, 60–72]; all men). Median follow-up was 13.4 months (range, 2.1–24.2) for cohort A and 17.0 months (range, 1.8–22.9) for cohort B. In cohort A, 6- and 12-month RFS rates were 95.2% and 73.4%, respectively. In cohort B, the 3-month cCR rate was 100%, and the median DOR was not reached (range, 1.7–19.7 months). All patients experienced treatment-related adverse events (TRAEs); 4 patients (14.3%) had grade ≥ 3 TRAEs. The most common TRAEs were elevated alanine aminotransferase (42.9%), alopecia (42.9%), and fatigue (35.7%). Exploratory analysis of baseline utDNA status demonstrated significant prognostic stratification, with positive patients exhibiting inferior 1-year RFS compared to those with negative status (50% vs. 91%, P=0.043). Conclusions: DV demonstrated a manageable safety profile and encouraging efficacy in patients with HR-NMIBC and HER2 overexpression in both adjuvant and rescue settings. The trial is ongoing, following a Simon two-stage optimal design, with a target enrollment of 52 patients in cohort A and 25 in cohort B. Study initiation was in May 2023. Clinical trial information: NCT05996952 .
Epidemiological trends and burden of liver cancer mortality due to hepatitis B in South Asia: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.
e16209 Background: Hepatitis B virus (HBV) remains a major driver of liver cancer mortality in South Asia. Despite the availability of effective vaccination and antiviral therapies, the long-term regional and country-specific mortality trends attributable to HBV remain inadequately characterized. We aimed to evaluate temporal trends and forecast future mortality burden across South Asia. Methods: We conducted a retrospective population-based analysis of age-standardized mortality rates (ASMRs) for liver cancer attributable to hepatitis B from 1990 to 2023 across South Asia, using the Global Burden of Disease 2023 database, stratified by country and sex. Temporal trends were quantified using estimated annual percentage change (EAPC) with 95% confidence intervals (CIs). Advanced machine-learning–based time-series models were applied to forecast ASMRs through 2050, with uncertainty assessed using prediction intervals. Results: From 1990 to 2023, liver cancer mortality attributable to hepatitis B demonstrated a significant increasing trend in South Asia overall (both sexes EAPC 0.46; 95% CI 0.27–0.65). Rising trends were observed in both females (EAPC 0.58; 95% CI 0.41–0.75) and males (EAPC 0.56; 95% CI 0.35–0.77), with consistently higher ASMRs among males. Country-specific analyses revealed the steepest increases in Pakistan (both sexes EAPC 0.55), Nepal (0.54), and India (0.46). Bangladesh showed a divergent pattern, with increasing mortality among males (EAPC 0.21; 95% CI 0.05–0.37), while female mortality remained relatively stable (EAPC −0.13; 95% CI −0.45 to 0.19). Bhutan exhibited modest and largely non-significant changes across sexes. Forecasting models project persistently elevated or rising ASMRs through 2050, particularly among males. Bangladesh and Bhutan are projected to maintain high male mortality burdens, while South Asia overall demonstrates widening prediction intervals beyond 2035. Conclusions: Liver cancer mortality attributable to hepatitis B is increasing across South Asia, with pronounced sex and country-level heterogeneity. Rising trends among males, particularly in Bangladesh, India, Pakistan, and Nepal, underscore critical gaps in HBV prevention, diagnosis, and long-term antiviral coverage. Location Sex EAPC Lower 95%CI Upper 95%CI Bangladesh Both 0.02 -0.19 0.22 Bangladesh Female -0.13 -0.45 0.19 Bangladesh Male 0.21 0.05 0.37 Bhutan Both 0.07 -0.22 0.37 Bhutan Female 0.20 -0.09 0.49 Bhutan Male 0.02 -0.26 0.31 India Both 0.46 0.26 0.66 India Female 0.58 0.38 0.78 India Male 0.56 0.35 0.78 Nepal Both 0.54 0.26 0.82 Nepal Female 0.14 -0.09 0.37 Nepal Male 0.81 0.53 1.10 Pakistan Both 0.55 0.41 0.69 Pakistan Female 0.96 0.75 1.17 Pakistan Male 0.29 0.17 0.41 South Asia Both 0.46 0.27 0.65 South Asia Female 0.58 0.41 0.75 South Asia Male 0.56 0.35 0.77
First-in-human study of BG-C9074 (B7-H4–targeting ADC) in advanced solid tumors: Dose escalation and safety expansion.
3013 Background: B7-H4, a transmembrane glycoprotein, has limited expression in normal tissue, but is upregulated in a variety of solid tumors. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4. We present results of monotherapy dose escalation and safety expansion from the ongoing phase 1 study. Methods: BG-C9074-101 (NCT06233942) is a first-in-human, multicenter study of BG-C9074 as monotherapy and in combination with other anticancer therapies in patients (pts) with advanced solid tumors. Pts with advanced solid tumors, irrespective of B7-H4 expression, received BG-C9074 IV every 3 weeks in escalating doses from 1 to 9 mg/kg. Endpoints included safety, preliminary antitumor activity (per RECIST v1.1) and pharmacokinetics. Results: As of Dec 29, 2025, 123 pts with advanced solid tumors received BG-C9074 monotherapy in phase 1a (ovarian [OC], n = 62; HR+/HER2- breast cancer, n = 28; triple negative breast cancer [TNBC], n = 18; cholangiocarcinoma, n = 11; endometrial, n = 3; squamous non-small cell lung cancer, n = 1). Median (range) prior lines were 4 (0-13). 8 pts experienced DLTs (thrombocytopenia [n = 2, 6.5 mg/kg; n = 1, 7 mg/kg], febrile neutropenia [n = 1, 6.5 mg/kg; n = 1, 7 mg/kg], neutropenic infection [n = 1, 7 mg/kg], fatigue [n = 1, 6 mg/kg], nausea [n = 1, 9 mg/kg], and unexplained death [n = 1, 9 mg/kg]). Treatment-related adverse events (TRAEs) occurred in 113 pts (91.9%); grade (gr) ≥3 in 30.1%. The most common TRAEs were nausea (53.7%; gr ≥3, 4.1%), neutrophil count decreased/neutropenia (44.7%; gr ≥3, 18.7%), and fatigue (37.4%; gr ≥3, 2.4%). Hematologic and gastrointestinal toxicities were manageable with dose modifications and/or supportive care. Among 114 efficacy-evaluable pts, confirmed ORR (cORR) was 28.1% (95% CI: 20.1-37.3), including 2 CRs (1 OC, 6.5 mg/kg, 1 TNBC, 5 mg/kg) and 30 PRs (Table); unconfirmed ORR was 33.3% (24.8-42.8; 3 CRs, 35 PRs). Responses were observed across doses and levels of B7-H4 expression, without consistent association of response with B7-H4 expression across tumor types. Median (range) study follow-up was 6.0 (0.3-17.7) months. ADC and free payload concentrations decreased in a biexponential manner with a half-life of ~7 days for ADC. Exposure for ADC and free payload increased approximately dose proportionally. Conclusions: BG-C9074 demonstrates a tolerable safety profile in pts with advanced solid tumors. Encouraging antitumor activity was observed in OC and TNBC. Dose expansion and optimization are ongoing. Clinical trial information: NCT06233942 . OC (n=55) TNBC (n=16) HR+/HER2- BC (n=28) Total (N=114) cORR, % (95% CI) 34.5(22.2-48.6) 31.3(11.0-58.7) 17.9(6.1-36.9) 28.1(20.1-37.3) CR, n (%) 1 (1.8) 1 (6.3) 0 (0.0) 2 (1.8) PR, n (%) 18 (32.7) 4 (25.0) 5 (17.9) 30 (26.3) SD, n (%) 32 (58.2) 5 (31.3) 16 (57.1) 60 (52.6) PD, n (%) 4 (7.3) 5 (31.3) 7 (25.0) 17 (14.9) Not evaluable, n (%) 0 (0.0) 1 (6.3) 0 (0.0) 5 (4.4)
Integrating tumor-infiltrating iymphocytes (TILs) in the biomarker landscape of gastroesophageal adenocarcinoma: Going beyond PD-L1.
4098 Background: Immune checkpoint inhibitors (CPI) are standard of care in perioperative and metastatic gastro-esophageal adenocarcinoma (GEA). PD-L1 scoring remains heterogeneous, with multiple assays and substantial interobserver variability. In breast cancer, immunotherapy responses occur even in PD-L1–negative tumors when tumor-infiltrating lymphocytes (TILs) are present. Exploratory analyses from CM649 suggest that immune infiltration and T-cell signatures may better capture CPI benefit than PD-L1 alone, particularly with ipilimumab–nivolumab. We evaluated TILs and their relationship with established biomarkers in a large GEA cohort. Methods: We performed a single-center retrospective study including localized and metastatic GEA patients diagnosed between 2019–2023. Histopathology included MMR status, HER2 (IHC/SISH), PD-L1 CPS, and CLDN18.2 (≥75% tumor cells). TILs were blindly reviewed by an expert pathologist using international TILs-WG guidelines (in press). Baseline characteristics and follow-up were collected until August 2024. Results: A total of 230 patients were included (140 localized, 90 metastatic). MMR, PD-L1 CPS, CLDN18.2, and HER2 status were available for all. By Lauren classification, 83 tumors were diffuse (36%), 131 intestinal (57%), and 17 mixed (7%). TILs were dichotomized at < 20% and < 10%. TIL density differed significantly across Lauren subtypes (p = 0.0007): diffuse tumors showed markedly lower infiltration (76% with TILs < 20%) compared with intestinal tumors (60% with TILs ≥20%). Using the < 10% cutoff, diffuse tumors again showed lower immune infiltration (78% vs. 22%; p < 0.001). PD-L1 CPS categories ( < 1, 1–4, 5–9, ≥10) did not differ by subtype. Notably, in CPS < 1 tumors, 28/48 (58%) were TIL-high (≥10%), whereas CPS ≥10 tumors showed strong concordance with TIL-high status (25/30, 83%). HER2-positive tumors had a higher proportion of TIL-high cases than HER2-negative tumors (OR 3.55; 95% CI 1.64–8.39; p = 0.0004). CLDN18.2 positivity showed no association with TILs (p = 0.44; OR 0.80; 95% CI 0.46–1.37). Conclusions: Using international TILs-WG guidelines, TIL assessment is feasible in routine GEA pathology. TIL density varied significantly across Lauren subtypes, with diffuse tumors showing consistently low immune infiltration. PD-L1 CPS did not reflect these differences and showed substantial discordance with TILs, particularly in PD-L1–negative but TIL-high tumors, suggesting potential CPI sensitivity. HER2 positivity, but not CLDN18.2, was associated with higher TIL levels. These findings support further evaluation of TILs alongside PD-L1 CPS/TAP score as improved predictive biomarkers for anti-PD-1 or anti-PD-1/CTLA-4 therapy.
Older adults with extensive-stage small-cell lung cancer treated with first-line chemoimmunotherapy: Updated systematic review and meta-analysis.
e20152 Background: Small-cell lung cancer (SCLC) accounts for ~10–15% of lung cancers, and most patients present with extensive-stage disease (ES-SCLC) with poor survival. PD-1/PD-L1 immune checkpoint inhibitors (ICIs) added to first-line platinum-etoposide have changed standard care, but older adults (≥70 years) remain underrepresented despite forming a large real-world ES-SCLC population. With newer data and longer follow-up now available, we updated prior evidence to better define outcomes in older patients treated with ICI–chemotherapy. Methods: Following PRISMA principles, we searched multiple electronic databases from inception through January 5 for randomized trials of first-line platinum–etoposide with vs without PD-1/PD-L1 ICIs. The most mature report per trial was used. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Random-effects meta-analysis pooled hazard ratios (HRs) with heterogeneity assessed by I²/τ²; funnel plots and leave-one-out analyses. Results: Ten studies contributed OS. ICI–chemotherapy significantly improved OS versus control (HR 0.79, 95% CI 0.71–0.89), with moderate heterogeneity (I² 31.8%, τ² 0.0096; p = 0.154) and a prediction interval of 0.61–1.02. Four studies contributed PFS, demonstrating improved PFS (HR 0.67, 95% CI 0.60–0.74) with low heterogeneity (I² 10.4%, τ² 0.0013; p = 0.341) and a prediction interval of 0.54–0.82. Leave-one-out analyses showed stable effects, and funnel plots did not suggest major small-study effects. Conclusions: In updated randomized evidence, adding PD-1/PD-L1 ICIs to first-line platinum- etoposide provides clinically meaningful improvements in both OS and PFS, with low-to-moderate heterogeneity. These findings support continued use in older adults while emphasizing the need for better age-stratified reporting and dedicated studies to refine patient selection.
Integrating tumor growth models to improve late-stage lung cancer outcome prediction using early-stage clinical trial data.
8532 Background: Immunotherapy has substantially improved clinical outcomes but poses distinct challenges for response assessment due to heterogeneous and non-monotonic tumor kinetics. RECIST 1.1 rely on unidimensional lesion measurements that may incompletely capture spatial heterogeneity which can result in limited characterization of tumor growth. Tumor growth modeling provides a complementary, quantitative framework for capturing longitudinal tumor dynamics. Different frameworks have been proposed to model total disease progression and response to treatment from total tumor volume. However, model selection may be challenging with each model capturing distinct growth mechanisms. In this work, we present a framework integrating complementary tumor growth models using a neural network classifier to predict late-stage outcomes from early-stage timepoints. Methods: We retrospectively aggregated deidentified data from 417 anonymized subjects with metastatic non-small cell lung cancer (NSCLC) treated with immunotherapy. Serial CT datasets were acquired at five timepoints over a 30-week period and lesions were annotated by expert radiologists according to RECIST 1.1 criteria. Tumor burden was derived from radiologist annotations using a previously validated AI method that reconstructs 3D lesion volumes from bidimensional data. For each subject, Modified Gompertz (MG) and Stein-Claret (SC) models were implemented to estimate intrinsic tumor growth parameters. Both models were fitted using early on-treatment data up to 21 weeks and used to predict response to treatment at week 30. To evaluate complementarity and the ability of early tumor dynamics to predict radiological response, model parameters were combined and used to train a two-layer neural network for radiological outcome classification. Performance of the combined MG+SC was compared with single-model classifiers on response (CR/PR) vs non-response (SD/PD) and progression (PD) vs non-progression (CR/PR/SD) using accuracy and sensitivity metrics. Results: The cross-validated accuracy in classifying responders and non-responders at week 30 was 81.1% from the combined MG+SC model (sensitivity=79.2%; specificity=83.0%), higher than both individual models (accuracy = 77.8% and 68.0% for MG and SC respectively). The combined modeling framework confirmed higher accuracy (70.7%) when distinguishing progressive disease from the non-progressor group (sensitivity=64.5%, specificity=76.5%) when compared to both MG (69.1%) and SC (66.8%). Conclusions: This work showed that integrating early-stage dynamics from complementary mechanistic growth models improves week-30 radiographic outcome prediction over individual models in metastatic NSCLC immunotherapy trials. This framework can enable earlier identification of patient-level response that may support treatment adaptation.
Noninvasive detection of early gastric cancer via red blood cell DNA features associated with tumor-induced hematopoietic stress.
4093 Background: Early detection of gastric cancer (GC) is limited by invasive endoscopy and the low sensitivity of current blood-based biomarkers for early-stage disease. Emerging evidence indicates that GC engages in complex crosstalk with the bone marrow microenvironment, imposing stress on hematopoiesis. Tumor-derived exosomal and inflammatory mediators reprogram transcriptional and epigenetic profiles in hematopoietic progenitors, driving abnormal hematopoiesis and inducing genomic instability. Here, we report a noninvasive strategy for GC detection based on genome-wide profiling of DNA remnants in mature red blood cells (rbcDNA) and validate its performance for early-stage disease across independent multicenter cohorts. Methods: We analyzed rbcDNA from 1–2 mL peripheral blood of 865 individuals, including 434 treatment-naive patients with stage I–III GC (~60% stage I) and 431 non-GC controls with benign gastric conditions. Shallow whole-genome sequencing revealed reproducible rbcDNA read-depth features that distinguished GC from non-cancer states. A machine-learning classifier was trained on dimensionally reduced rbcDNA features in a discovery cohort (n = 435), with a cutoff fixed at 90% specificity. The locked model was then evaluated in a test cohort (n = 109) and three independent validation cohorts from distinct medical centers (n = 321). Results: In a discovery cohort, we identified GC-associated rbcDNA features that were significantly enriched in hematopoietic regulation and cell-cycle pathways, reflecting systemic hematopoietic stress rather than tumor-derived copy-number alterations. The resulting classifier achieved AUCs of 93% in the discovery cohort and 95% in the test cohort. At the predefined cutoff, the classifier yielded 83% overall sensitivity and 79% sensitivity for stage I GC in the test cohort. Across three independent medical center cohorts, the model achieved sensitivities of 83%, 90%, and 86%, with specificities ranging from 89% to 94%, consistent with the discovery and test cohorts. The assay effectively distinguished early-stage GC from precancerous lesions, including atrophic gastritis and intestinal metaplasia, while showing limited detection in non-gastric solid tumors. Importantly, rbcDNA identified ~80% of GC cases that were negative for conventional serum tumor markers. Conclusions: These findings establish rbcDNA as an effective biomarker for accurate, noninvasive detection of early-stage GC.
Survival outcomes of neoadjuvant endocrine therapy versus chemotherapy in hormone receptor–positive breast cancer: An NCDB analysis.
e12669 Background: Neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NCT) are accepted treatment strategies for postmenopausal women with hormone receptor–positive (HR+), HER2-negative invasive breast cancer (IBC). Contemporary comparisons of surgical outcomes and survival remain limited. Methods: Women aged ≥50 years with stage II–III, HER2-negative (IHC 0–1+ or 2+/FISH-negative), HR+ IBC diagnosed from 2010–2017 were identified from the NCDB. Patients received NET or NCT followed by surgery and adjuvant endocrine therapy were included. Overall survival (OS) was analyzed using Kaplan–Meier methods and multivariable Cox regression Results: Among 6,857 patients, 1,619 (23.6%) received NET and 5,238 (76.4%) received NCT. NET was independently associated with older age, higher comorbidity burden, government insurance, greater travel distance ( > 200 miles), and T2 tumors, while NCT was associated with community facility treatment, higher tumor grade, and greater nodal involvement. NET was associated with lower odds of mastectomy compared with NCT (19.4% vs 80.6%; adjusted odds ratio [aOR] 0.63, 95% CI 0.53–0.75). Adjuvant radiation use did not differ after adjustment. NET was associated with lower odds of achieving at least a partial response (aOR 0.58, 95% CI 0.44–0.76), although longer NET duration ( > 115 days) was associated with reduced mastectomy rates. Median follow-up was 178 months with similar median OS; 5 yr survival at 94.6% vs 95.2%, 9 yr survival at 48.6% vs 52.1% for NET vs NCT respectively. NCT conferred a modest survival advantage in the full cohort (adjusted hazard ratio [HR] 0.89, 95% CI 0.81–0.98; p = 0.016) and in ER+/PR+ tumors (HR 0.85, 95% CI 0.77–0.94; p = 0.002), with no difference in single HR-positive disease. Conclusions: NET is preferentially used in older, more comorbid patients and those with geographic or socioeconomic barriers and is associated with lower mastectomy rates and largely comparable survival to NCT. Interpretation is limited by the retrospective design, potential selection bias, availability of Oncotype DX only in subset of pts, and lack of specific therapy used.
Final results of Alliance A031902: A phase III trial of enzalutamide plus rucaparib as first-line therapy in metastatic castration-resistant prostate cancer (CASPAR).
5069 Background: Inhibition of androgen receptor (AR)-signaling results in increases in double-strand DNA breaks and genomic instability. PARP inhibitors (PARPi) are a standard treatment option for patients (pts) with homologous recombination repair mutations (HRRm). Combinations of PARPi and AR pathway inhibitors (ARPI) are associated with synthetic lethality in multiple pre-clinical studies. Clinical trials have suggested potential benefits with co-targeting PARPi and ARPI in pts with and without HRRm. Methods: Alliance A031902 compared radiographic progression-free survival (rPFS) and overall survival (OS) as co-primary endpoints with enzalutamide and rucaparib (Enz/Ruca) versus enzalutamide plus placebo (Enz/Plac) for pts with metastatic castration resistant prostate cancer (mCRPC) regardless of BRCA/HRRm status. This trial was conducted by the Alliance for Clinical Trials in Oncology in 36 centers in the US. Target sample size was 1,002 patients. Eligibility required mCRPC with or without measurable metastatic disease and was agnostic regarding HRRm status. The trial was discontinued in 10/2023 due to changes in the treatment landscape for this pt population. Results: Between 10/21 and 4/23, 61 pts were randomized to Enz/Ruca (n=30) or Enz/Plac (n=31). Known BRCA1/2 or PALB2 mutations were present in 1 pt (3.3%) in the Enz/Ruca arm and 1 pt (3.2%) in the Enz/Plac arm; wildtype in 14 (46.7%) vs 15 (48.4%), and unknown in 15 (50%) vs 15 (48.4%), respectively. Three patients (11.5%) in the Enz/Ruca arm discontinued due to an adverse event (AE) vs 0 in the Enz/Plac arm. Among response-evaluable pts, 7/26 (27%) in the Enz/Ruca arm discontinued due to disease progression vs 10/31 (33%) in the Enz/Plac arm. Most common grade 3+ AEs were anemia (33% vs 3%) and hypertension (17% vs 10%) in the Enz/Ruca arm and Enz/Plac arm, respectively. All 61 pts were evaluable for response assessment. PSA declines ≥50% and ≥90% were observed in 79% vs 45% and 60% vs 43% of pts receiving Enz/Ruca versus Enz/Plac, respectively. Median PFS in the Enz/Ruca vs Enz/Plac arms was 17.1 vs 14.2 mos, respectively (HR 1.13 [95% CI: 0.42-3.01], p=0.81), median rPFS (inclusive of unequivocal clinical progression) was 17.1 vs 11.7 mos ( HR 0.72; 95% CI: 0.31-1.67, p = 0.44), and median OS was not reached vs 27.0 mos (HR 0.65; 95% CI: 0.29-1.45, p=0.29). Conclusions: In this prematurely terminated phase III study, Enz/Ruca was generally well tolerated, with the safety profile consistent with prior PARPi/ARPI combinations. Efficacy outcomes for rPFS and OS are inconclusive due to limited sample size. Definitive conclusions regarding the clinical benefit of this combination cannot be determined from this study. Clinical trial information: NCT04455750 .
Cardiovascular safety planning in NCCN-cited breast cancer trials: Audit and surveillance framework.
e24022 Background: Cardiovascular (CV) and venous thromboembolism (VTE) risks differ across systemic breast cancer therapies. NCCN-cited trials underpin treatment recommendations but may embed inconsistent CV and VTE safety surveillance. Methods: Audit of phase II–III systemic-therapy trials cited in NCCN Breast Cancer Guidelines. We created a novel scoring system CVERQ-BC (Cardiovascular evaluation and reporting quality in Breast Cancer) (scored 0–12), capturing reported baseline CV risk; baseline imaging; prespecified serial imaging; baseline ECG; troponin/NP strategy; quantitative CV endpoint definitions; prespecified CV endpoints; central adjudication; CV AE grading; inclusion of stable CVD; BP monitoring with HTN criteria; CV dose-mod/hold rules. VTE score (0–3) captured validated VTE risk models, protocolized prophylaxis, and prespecified objective VTE endpoints. CVERQ-BC scoring was based on review of trial publications, full texts, study protocols, and trial registrations. Two independent reviewers scored each trial, with discrepancies resolved by consensus. Analyses were descriptive with exploratory comparisons by class, era, and sponsor. Results: We included 129 unique trials (1990–2026); 49.6% were industry-sponsored. Median CVERQ-BC was 2 (IQR 2–4); 56.6% scored ≤2 and 6.2% ≥8. Key CV elements were infrequently reported: baseline CV risk (28.7%), baseline imaging (32.6%), prespecified follow-up imaging (24.8%), ECG surveillance (10.9%), biomarker strategy (3.1%), prespecified CV endpoints (26.4%), and central adjudication (10.9%). CVERQ-BC did not differ by sponsor type (p = 0.39) or era among industry trials (p = 0.31). By class (median [IQR]): HER2-directed 6.0 [4.5–7.5], anthracycline 3.0 [2.0–6.0], taxane 3.0 [2.0–6.0], fluoropyrimidine 2.0 [2.0–5.0], alkylator 2.0 [1.25–5.0], platinum 2.0 [2.0–3.5], endocrine 2.0 [2.0–4.0], CDK4/6 inhibitor 2.0 [2.0–3.5]. In HER2-directed trials, baseline and serial cardiac imaging was reported in 77.8% (21/27), explicit quantitative CV endpoint definitions in 77.8% (21/27), and prespecified CV endpoints in 70.4% (19/27). Outside HER2-directed evidence, mechanism-aligned safety domains were uncommon, with QTc or ECG surveillance in QT-liability tyrosine kinase inhibitor and CDK4/6 inhibitor trials, blood pressure criteria in VEGF or VEGFR-directed regimens, and ischemia monitoring in fluoropyrimidine trials each reported in 20% or fewer studies. Conclusions: Reported CV/VTE safety planning in NCCN-cited trials is heterogeneous and concentrated in HER2-directed evidence. Without guideline-specified class-adapted surveillance standards (and possible under-reporting), variability may underestimate cardiotoxicity and limit generalizability to patients with baseline CVD. CVERQ-BC provides a reproducible, class-adapted checklist for trial protocols, reporting, and guideline citation.
Access to trastuzumab deruxtecan for HER2-low metastatic breast cancer in Brazil’s Unified Public Health System: A population-impact model.
1539 Background: HER2-low disease has recently emerged as a distinct, targetable category in metastatic breast cancer (MBC), with trastuzumab deruxtecan (T-DXd) demonstrating a clinically meaningful overall survival (OS) benefit. In Brazil, however, access to innovative oncology therapies within the Unified Health System (SUS) is frequently delayed. We quantified the population-level consequences of delayed access to T-DXd for patients with HER2-low MBC. Methods: We conducted a nationwide population-impact analysis from the public-payer perspective, combining Brazilian epidemiologic data with survival benefit estimates derived from randomized clinical trials, using an exponential approximation to model long-term outcomes under delayed-access scenarios. An annual eligible cohort was constructed stepwise from incident MBC (21,133/year), applying: SUS dependence (proxy: 1 - private coverage, p=0.759), HER2-low prevalence (p=0.320), HR+ proportion among HER2-low (proxy using luminal status, p=0.747), and probability of reaching the eligible line of therapy (p line=0.50). Treatment effect inputs were taken from the DESTINY-Breast04 HR+ subgroup (median OS 23.9 vs 17.5 months. OS HR=0.64 [95% CI 0.48–0.86]). Primary outcome was preventable deaths/year, computed as treated/year × (1 − HR), where treated/year equals the annual eligible cohort multiplied by uptake (95%, 75%, 50%). A sensitivity range for preventable deaths was generated by varying HR across its trial-reported 95% CI. Life-years gained over 10 years were estimated as treated/year × 10 × Δmedian OS (years). One-way sensitivity varied p (HER2-low) from 0.25 - 0.46 (uptake fixed at 95%). Results: The modeled annual eligible cohort was 1,917 patients/year, treated/year was 1,821 (95% uptake), 1,438 (75%), and 959 (50%). Estimated preventable deaths/year were 656 (range 255-947), 518 (201-748), and 345 (134-498), corresponding to 6,560, 5,180, and 3,450 deaths avoided over 10 years, respectively. Life-years gained over 10 years were 9,713, 7,668, and 5,112 across the three uptake scenarios. Varying p(HER2-low) from 0.25-0.46 yielded 513-943 preventable deaths/year and 7,588-13,962 life-years gained (10 years) at 95% uptake. Conclusions: Delayed access to T-DXd within Brazil’s public health system may result in substantial, avoidable mortality among patients with HER2-low MBC. These findings highlight the urgent need for accelerated incorporation pathways, consistent HER2-low testing, and operational readiness to translate proven survival gains into real-world benefit. Scenario Uptake Treated/year Preventable deaths/year Range (HR 95% CI) Life-years gained (10 years) Base-case (95%) 95.0% 1,821 656 255 – 947 9,713 Moderate (75%) 75.0% 1,438 518 201 – 748 7,668 Conservative (50%) 50.0% 959 345 134 – 498 5,112
Breast cancer care in Armenia: An assessment of diagnostic and treatment capacity.
e13623 Background: Timely diagnosis and access to treatment are essential components of effective breast cancer care. Despite a growing breast cancer burden in Armenia, the availability of diagnostic and treatment services has not been comprehensively evaluated. We implemented a survey at health centers in Armenia to assess the availability of diagnostic and treatment modalities for breast cancer. Methods: We conducted a cross-sectional descriptive cohort study, employing a validated breast cancer survey adapted and translated into Armenian from the Tanzania Breast Health Care Assessment 2017 and the Sergipe 2018: Breast Healthcare Assessment. In collaboration with administrators at Armenia’s National Center of Oncology, three tertiary hospitals and one breast care facility in Yerevan, the capital city, were selected for participation in this study. These institutions were determined to be representative of the highest-capacity sites for breast cancer treatment in the country. The study was reviewed by the Yerevan State Medical University and UCLA Medical School institutional review boards and deemed exempt from human subjects research. Results: All sites reported functional MRI, ultrasound, and CT capabilities; three operate an MRI with a dedicated breast coil. Only one PET scanner is available nationwide, and is located at one of the participating institutions. All four sites reported performing breast surgery, three reported use of immunotherapy, and two reported access to radiation therapy. No site endorsed possessing a Cobalt-60 unit, and only one site reported having a linear accelerator (LINAC). Most surveyed antineoplastic agents were available at three institutions; methotrexate was reported at only one site. Two sites included gene profiling in the pathology report, two conducted BRCA 1/2 testing, and two performed bone scans. Three sites performed sentinel lymph node biopsy with blue dye, and two used radiotracer techniques. Conclusions: Diagnostic and treatment capacity for breast cancer varies across institutions in Armenia. While most surveyed diagnostic and therapeutic modalities were available at at least one site, limited access to certain advanced technologies and uneven distribution of services may require patients to seek care across multiple institutions. As this assessment reflects resource availability rather than utilization, further evaluation of patient- and system-level barriers is needed to contextualize breast cancer outcomes in Armenia.
Strengthening supportive care–patient guidance oncology models for adolescents and young adults with cancer: A community-based approach by Gunvati Jagan Nath Kapoor Foundation GJK.
e23062 Background: Adolescents and Young Adults (AYA) with cancer face unique clinical, psychosocial, and socioeconomic challenges that significantly affect treatment adherence, quality of life, and long-term survivorship outcomes. Despite advances in cancer therapy, supportive care services for AYA patients remain fragmented and under-prioritized, particularly in low- and middle-income settings. The GJK model for Patient Guidance is tailored specifically for AYA cancer patients, in this aspect specifically the testicular patients. GJK’s Guidance framework adopts a holistic, patient-centered approach integrating psychosocial counselling, treatment navigation, financial guidance, stakeholder connect, and caregiver engagement. The model emphasizes early intervention from diagnosis through treatment and survivorship, with a strong focus on mental well-being, and social reintegration. Digital engagement tools, and partnerships with oncology centers enable scalable and sustainable delivery of services. Methods: Our model is integrated within the hospital healthcare system. Patients received psychosocial interventions in form of services such as documentation assistance, financial guidance, emotional support, navigation, linkages, financial aid, accommodation guidance so that they do not abandon treatment. Results: Between 2020 and 2025, 2394 patients with urological malignancies were referred for psychosocial support, of whom 606 (25%) were diagnosed with Germ Cell Tumors (GCT). The majority of GCT patients 537 (89%) were adolescents and young adults aged 15–39 years. Treatment compliance was observed in 484 (80%) of GCT patients. A total of 8097 psychosocial support services were delivered, with patients accessing an average of 3–4 visits during active treatment. ₹3,79,09,000 funds were raised through various stakeholders to effectively help with treatment costs for these patients. Digital engagement and survivors meet led to 474 patients served and provided a platform to empower and create a platform for survivors to create a peer network. Conclusions: Program insights demonstrate improved patient engagement, reduced treatment abandonment, enhanced emotional well-being, and better coordination between clinical and other stakeholders in the health system. The GJK Patient Guidance model highlights the importance of age-appropriate, culturally sensitive supportive care interventions for AYA patients and underscores the role of a non-profit in bridging critical gaps in oncology care. This initiative advocates for the systematic integration of AYA-focused supportive care within oncology programs and offers a replicable framework to strengthen patient services across diverse healthcare settings, enhance adherence and optimize clinical outcomes.
Identification and frequency of <i>EGFR</i> mutations among NSCLC patients in Nigeria: Preliminary findings.
e20057 Background: Epidermal Growth Factor Receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), particularly adenocarcinoma, are predictive biomarkers for response to EGFR tyrosine kinase inhibitors (TKIs). However, data from sub-Saharan Africa remain limited, contributing to under-representation in global precision oncology frameworks and restricting evidence-based treatment decision-making in the region. This study aims to determine the frequency and and molecular spectrum of EGFR mutations among Nigerian patients with lung adenocarcinoma and to generate locally relevant evidence to inform precision oncology strategies. Methods: This ongoing multi-center study analyzed formalin-fixed paraffin-embedded (FFPE) tumor tissue from 124 patients diagnosed with NSCLC, (lung adenocarcinoma) across Nigeria. DNA was extracted and subjected to real-time polymerase chain reaction (RT-PCR) using a mutation-specific assay panel optimized to detect alterations in EGFR exons 18–21, including exon 19 deletions, L858R, L861Q, G719X, S768I, exon 20 insertions, and the resistance mutation T790M. Results: EGFR-sensitive mutations were identified in 48 of 124 samples (38.70%). Mutation prevalence was notably higher among females (24.19 %) compared to males (14.51%). Exon 19 deletions and the L858R point mutation in exon 21 accounted for the majority (89.58 %) of all EGFR mutations detected. Less frequent mutations included exon 20 insertions, G719X, and T790M (10.42 %), while no mutations were detected in L861Q. Conclusions: A high proportion of Nigerian patients with lung adenocarcinoma harbor actionable EGFR mutations, with a mutation spectrum comparable to that reported in other global populations. These findings provide critical locally generated evidence supporting routine EGFR testing and underscore the urgent need to expand access to molecular diagnostics and targeted therapies in Nigeria. Integrating biomarker-driven care into national cancer control strategies is essential to advancing equitable precision oncology in sub-Saharan Africa.
Impact of the Navya Earthshot–enabled clinical decision support system on treatment turnaround time in oncology care: A real-world study from a tertiary cancer center in India.
1588 Background: Delays in Oncology care often result from systemic inefficiencies and patient-related barriers, leading to delayed treatment decision. Navya Earthshot is a validated Artificial Intelligence (AI) enabled clinical decision support system that matches patient records to standard-of-care oncology guidelines to generate evidence-based treatment recommendations. This study evaluated the real-world impact of Navya Earthshot implementation at a Tertiary Cancer Centre in India on turnaround time (TAT) for cancer directed treatment decision. Methods: This was a prospective, pre–post observational study conducted in two phases at a tertiary cancer centre in India. Baseline data collected prior to Navya Earthshot integration (December 2023–February 2024; n = 148) were compared with data from the post-implementation phase (February 2025–May 2025; n = 488). Navya Earthshot was embedded into routine clinical workflows, matching patient-specific clinical information to National Cancer Grid (NCG) guidelines to generate treatment options. These recommendations were reviewed by treating oncologists and discussed in daily multidisciplinary tumour boards. Patients were tracked from registration through diagnostic completion to treatment decision. The primary outcome was the turnaround time (TAT) for treatment decision, defined as the number of days from patient registration to treatment decision. Statistical comparisons were performed using the Mann–Whitney U test, with significance set at p < 0.05. Results: A total of 636 patients were included in the analysis, with 148 (pre-implementation phase) and 488 (post-implementation phase). Median TAT decreased from 21.4 Interquartile Range (IQR) days pre-implementation to 16.73 days (IQR) post-implementation, representing a 21.8% reduction ( p < 0.05). The use of the Navya Earthshot decision support system was associated with a statistically significant reduction in overall TAT. This reduction reflects faster progression from patient registration through diagnostic completion to treatment decision in the post-implementation cohort. Conclusions: Integration of Navya Earthshot-enabled decision support system significantly improved treatment decision timelines in a high-volume public oncology setting. These findings demonstrate that scalable, guideline-aligned, patient-centric AI solutions can enhance workflow efficiency and strengthen end-to-end cancer care delivery in resource-constrained environments. Impact of Navya Earthshot implementation on turnaround time for treatment decision. Metric Pre-ImplementationPhase Post- ImplementationPhase % Change p-value Turnaround Time (TAT) 21.4 days 16.73 days ↓ 21.8% <0.05