Browse Articles
Discover research articles across all indexed journals
Phase II trial of SYS6010, an EGFR antibody-drug conjugate (ADC) in patients with advanced esophageal squamous cell carcinoma (ESCC).
4047 Background: SYS6010 is an EGFR- ADC composed of an EGFR-specific antibody, a cleavable linker, and the topoisomerase I inhibitor (TOPOi) JS-1. Preliminary clinical data from the phase I study of SYS6010 monotherapy in patients with solid tumors showed an acceptable safety and encouraging preliminary efficacy (ChiCTR2300072141). Here, we report the efficacy and safety results of SYS6010 in patients with ESCC in the phase II trial. Methods: Patients with advanced ESCC that was refractory or intolerant to standard therapy were enrolled. In the dose-expansion part, SYS6010 was administered intravenously at a dose of 3.6 mg/kg every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) assessed by the investigator. Results: As of Jan 14, 2026, 48 patients with ESCC (median age, 64.5 years; male, 89.6%; ECOG PS 1, 87.5%; metastatic disease, 93.8%) were enrolled and received SYS6010. Ten patients (20.8%) had received ≥3 prior lines of systemic therapy. The median follow-up was 3.9 months (mo; Q1-Q3: 3.1-5.6). Among 40 efficacy-evaluable patients, the confirmed ORR (cORR) was 35% (95%CI 20.6-51.7), and the disease control rate (DCR) was 67.5% (95%CI 50.9-81.4). Median progression-free survival (mPFS) was 4.6 mo (95% CI, 2.7–NR; 48% maturity). The 3-mo and 6-mo PFS rates were 56.3% and 41.4%, respectively. 15 patients remain on treatment with SYS6010. For TOPOi-naïve patients (n = 34), cORR and DCR were 41.2% (95%CI 24.7-59.3) and 70.6% (95%CI 52.5-84.9), respectively. mPFS was 4.6 mo (95%CI 2.8-NR; 45% maturity), with 3-mo and 6-mo PFS rates of 62.5% and 43.2%, respectively. 14 patients remain on treatment with SYS6010. Overall, 97.9% (47/48) of patients experienced treatment-related adverse events (TRAEs). Grade ≥3 TRAEs occurred in 31 (64.6%) patients. Common grade ≥3 TRAEs (≥5%) included neutropenia (29.2%), anemia (18.8%), leukopenia (18.8%), thrombocytopenia (12.5%), lymphocytopenia (8.3%), vomiting (8.3%), and nausea (6.3%). TRAEs led to treatment discontinuation in 4 (8.3%) patients. One death of unknown reason was reported and assessed by the investigator as related to the study drug. Conclusions: SYS6010 demonstrated a manageable safety profile and promising antitumor activity, supporting further development in patients with advanced ESCC, especially TOPOi-naïve patients. A phase 3 study is planned to compare SYS6010 with standard of care (SOC) in patients with TOPOi-naïve ESCC. Clinical trial information: ChiCTR2500099933.
Dose optimization in FDA oncology drug approvals: Factors associated with observing exposure-efficacy relationships.
e15127 Background: Exposure–response analysis has been recognized as a fundamental component in dose selection, optimization, and regulatory decision making across all phases of drug development. Our previous research has identified that when exposure–efficacy (E-E) relationships are observed, the likelihood of being subject to postmarketing requirements (PMRs) or postmarketing commitments (PMCs) related to dose optimization is significantly reduced. For successful E-E analyses, this study primarily evaluated the association between the number of dose levels used in E-E analyses and the observation of E-E relationships, and secondarily identified factors associated with observing E-E relationships in single-dose analyses. Methods: New oncology drugs approved in the United States between 2010 and 2024 were evaluated. Data were sourced from the publicly available Drugs@FDA database. The association between observation of E-E relationships and evaluated dose levels was assessed using odds ratios with 95% confidence intervals. Factors associated with observation of E-E relationships in a single dose evaluation were analyzed using logistic regression. Results: The analysis included 139 drugs, with 86 (61.9%) using a single dose and 53 (38.1%) using multiple dose levels for E-E analysis (Table 1). The association between observation of E-E relationship and multi-dose E-E analysis was statistically significant (χ² = 7.71, df = 1, p = 0.0055), with an odds ratio of 2.78. (95% CI: 1.34–5.78). In the analysis of factors associated with observing E-E relationships in a single dose evaluation, antibody based targeted drugs were identified as a significant factor using a logistic regression model. Conclusions: Our study revealed that the E-E relationships were evaluated using a single-dose for the majority of drugs (61.9%). E-E analysis conducted across multiple dose levels were strongly associated with a higher likelihood of observing E-E relationships. These findings highlight the importance of evaluating E-E analysis using multiple dose levels, which may help reduce the risk of being subject to PMRs and PMCs related to dose optimization. In addition, our study indicates that E-E relationships were more likely to be observed for antibody based targeted drugs, even though the analysis was conducted in a single dose level. Observation of E-E relationships and dose levels used in the analysis. E-E relationships were observed E-E relationships were NOT observed Total Multiple dose levels 38 15 53 Single dose 41 45 86 E-E, exposure–efficacy.
Fruquintinib plus FOLFIRI or mFOLFOX6 as second-line therapy for patients with <i>RAS</i> -mutant metastatic colorectal cancer (mCRC): A phase II, multicenter, open-label study.
3528 Background: Nearly half of metastatic colorectal cancer (mCRC) patients harbor RAS mutations, and the standard second-line regimen for this substantial subgroup of patients is combination chemotherapy (FOLFIRI/FOLFOX) with bevacizumab, which offers limited efficacy. Fruquintinib, an oral VEGFR-1, -2, and -3 inhibitor, has shown efficacy in refractory mCRC. This study evaluated the efficacy and safety of fruquintinib in combination with FOLFIRI or FOLFOX as second-line therapy for patients with RAS-mutant mCRC. Methods: This multicenter, open-label, single-arm phase II trial enrolled patients with RAS mutant mCRC who had failed first-line standard therapy. Participants received fruquintinib (4 mg once daily, days 1-21) plus FOLFIRI or mFOLFOX every 28 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: As of Nov 11, 2025, 42 eligible pts were enrolled and received at least one cycle of treatment. Baseline characteristics included median age (63.0 [range: 35-74]), male (59.5%), ECOG PS 1 (66.7%), left-sided (73.8%), liver metastasis (59.5%), prior anti-VEGF therapies (73.8%). The median PFS was 8.1 months (95% CI: 6.18, 9.46) and median OS was not reached yet. The Kaplan-Meier estimates for PFS rates at 3, 6, 9, and 12 months were 85.3%, 73.5%, 35.9%, and 15.4%, respectively. In the subgroup analysis, median PFS were longer in pts without liver metastases (8.4mo vs 6.4mo, HR: 1.65, 95%CI: 0.65-4.18), those with left-sided lesion (8.1mo vs 4.8mo, HR: 2.14, 95%CI: 0.79-5.77) and pts without prior anti-VEGF therapies (8.4mo vs 6.5mo, HR: 1.79, 95%CI: 0.59-5.36). The ORR was 52.5% (21/40) which consisted of CR 5% and PR 47.5%. The DCR was 97.5% (39/40). Additionally, the most common any grade treatment-emergent adverse events (TEAEs) were hypertension (23.8%), diarrhea (19.1%), and mucositis (19.1%). Grade ≥3 TEAEs was 14.3% including diarrhea (4.8%), intestinal obstruction (2.4%) and leukopenia (2.4%). Conclusions: Fruquintinib combined with either FOLFIRI or mFOLFOX6 as second-line therapy for patients with RAS-mutant metastatic colorectal cancer (mCRC) demonstrated promising efficacy and a manageable safety profile. Clinical trial information: NCT05634590 .
Impact of dedicated care coordination on access to multidimensional support services in young-onset colorectal cancer: A pragmatic trial.
11008 Background: The incidence of young-onset colorectal cancer (YOCRC) is increasing, and affected patients experience distinct challenges. YOCRC patients may benefit from a dedicated care coordinator that systematically assesses their unmet needs and facilitates referrals to multidimensional support services. Methods: In this pragmatic trial, we assigned newly diagnosed CRC patients aged <50 years who presented to a tertiary academic institution between 2023-2025 to usual multidisciplinary care, or usual care plus additional encounter(s) with a dedicated care coordinator as a part of the YOCRC program. Patient-reported concerns and distress were collected at initial presentation. The primary endpoint was the rate of utilization of support services designed to address multidimensional needs of YOCRC patients. Multivariable regression was performed to identify predictors of service utilization. Results: Among 1,250 YOCRC patients (mean age 42.8±6.0 years; 45.4% female; 77.3% white), 46.3% had rectal cancer. Emotional concerns were most common (41.0%), followed by physical (36.1%), practical (27.8%) and social (9.4%) concerns. The YOCRC coordinator successfully established contact with 604 individuals. Clinically significant distress (distress score ≥4) was reported by 27.4%, with no significant difference between groups (26.5% vs. 29.2%, p=0.34). Unmet service needs were reported by 39.1% in the intervention group, of whom 80.5% subsequently accessed corresponding support services. Patients with established contact with the YOCRC coordinator were more likely to access support services (Table 1, 72.5% vs.44.7%, p<0.001). On multivariable analysis, coordinator contact (aOR 1.48, 95%CI 1.22-1.80), rectal cancer diagnosis (aOR 1.36, 95%CI 1.13-1.62), and clinically significant distress (aOR 1.23, 95%CI 1.01-1.50) predicted greater multidimensional service utilization. Conclusions: YOCRC patients experience substantial emotional concerns and unmet needs. Integration of a YOCRC coordinator was associated with significantly increased utilization of multidimensional support services. This pragmatic trial supports a personalized, needs-driven care delivery model, that integrates patient-reported outcomes to further optimize targeted referrals. Multidimensional support services accessed by YOCRC patients with vs. without established contact with YOCRC coordinator. Contact Established (n=604) Contact Not Established (n=646) p Social Work 378 (62.6%) 288 (44.6%) <0.01 Genetics 229 (37.9%) 126 (19.5%) <0.01 Wound, Ostomy, Continence 196 (32.5%) 69 (10.7%) <0.01 Supportive care 92 (15.2%) 77 (11.9%) 0.09 Oncofertility 77 (12.7%) 39 (6.0%) <0.01 Integrative Medicine 73 (12.1%) 34 (5.3%) <0.01 Nutrition 46 (7.5%) 40 (6.2%) 0.32 Psychiatry 41 (6.8%) 19 (2.9%) <0.01 Adolescent and Young Adult Program 58 (9.6%) 29 (4.5%) <0.01
Association of skin cancer with Bruton tyrosine kinase inhibitors: A FAERS analysis.
e21551 Background: Bruton tyrosine kinase inhibitors (BTKis)—including Ibrutinib, Acalabrutinib, Zanubrutinib, and Pirtobrutinib—have revolutionized treatment of B-cell malignancies (e.g., CLL, MCL). However, secondary skin cancers have been increasingly reported in patients receiving BTKis. Preclinical and clinical evidence suggests BTKis (especially ibrutinib) may predispose patients to non-melanoma and melanoma skin cancers. We conducted a FAERS analysis to evaluate the association between BTKis and skin cancer risk. Methods: All reports in the FDA Adverse Event Reporting System (FAERS) from Q4 2013 through Q2 2025 listing a BTKi as a suspect drug were identified (N = 88,792). Skin cancer events were defined using relevant MedDRA preferred terms, including squamous cell carcinoma, basal cell carcinoma, and melanoma. The frequency and proportion of skin cancer reports were summarized for each BTKi and descriptively compared across agents. Results: Among 88,792 BTKi-associated reports, 413 skin cancer cases were identified (0.46%). Ibrutinib accounted for the majority of cases (n = 359), followed by Acalabrutinib (n = 42) and Zanubrutinib (n = 12); no skin cancer reports were identified with Pirtorutinib. Skin cancer reports predominantly occurred in older patients (≥65 years) and were more common in males. Across BTK inhibitors, skin cancer reports represented approximately 0.39–0.47% of total reported adverse events. Conclusions: Post-marketing surveillance data demonstrate a consistent signal of reported skin cancers among patients receiving BTK inhibitors, with the highest number of reports observed for Ibrutinib. While causality cannot be inferred from FAERS data, these findings highlight a potential class-associated safety concern and support the importance of routine dermatologic surveillance in patients treated with BTK inhibitors. Further prospective and real-world studies are warranted to better define absolute risk and underlying mechanisms. Skin cancer reports by BTK inhibitors. Drug Skin Ca cases (n) Skin Ca cases as % of BTKi AEs Ibrutinib 359 0.47% Acalabrutinib 42 0.39% Zanubrutinib 12 0.39% Pirtobrutinib 0 0% Total 413 0.46%
Beyond TMB: Characterizing tumor-intrinsic genomic architectures of immune resistance.
2586 Background: Immune checkpoint inhibitors (ICI) are increasingly selected based on tumor mutational burden (TMB); however, clinical benefit remains inconsistent. We hypothesized that tumor-intrinsic genomic alterations associated with immune suppression, immune exclusion, and antigen presentation failure frequently coexist with ICI-enabling biomarkers and define distinct resistance architectures. Methods: We analyzed tissue-based genomic profiling data from 7,773 solid tumors. TMB-high (TMB-H) tumors were evaluated for genomic alterations implicated in ICI resistance, including PTEN loss-of-function (LOF), STK11 and KEAP1 LOF, WNT /β-catenin pathway alterations ( CTNNB1 activating mutations, APC truncation/biallelic loss), B2M LOF (antigen presentation), JAK1/2 LOF (interferon signaling), and MDM2/MDM4 amplification. Results: Among 908 TMB-H tumors, 30.6% harbored at least one immune resistance–associated alteration. PTEN LOF was the dominant functional resistance event (7.6%) and represented the central hub in tumors with multiple resistance alterations (65.6%; 21/32). WNT pathway alterations were frequent, with APC truncation (15.9%; 144/908) exceeding CTNNB1 mutations (2.6%; 24/908), indicating heterogeneous modes of WNT activation. Importantly, WNT -driven tumors demonstrated divergent immune escape architectures: CTNNB1 -mutant tumors were enriched for B2M LOF (16.7%; 4/24), whereas APC -mutant tumors rarely harbored B2M loss (0.7%; 1/144), suggesting antigen presentation-dependent versus immune-exclusion-dominant resistance, respectively. Across the TMB-H cohort, increasing mutational burden was significantly associated with higher B2M LOF frequency (Wilcoxon rank-sum p = 3.6 × 10⁻⁶), consistent with immune editing under high neoantigen pressure. Interferon signaling alterations were rare ( JAK1 : 0.2%; 2/908; JAK2 : 0.0%; 0/908). Conclusions: TMB identifies immune pressure but not immune competence. Intrinsic ICI resistance in TMB high tumors is structured around a PTEN-WNT-B2M genomic axis, with distinct immune escape architectures determined by the mode of WNT activation. Integrating negative genomic predictors of immune response with established biomarkers may improve immunotherapy stratification and inform development of rational combination strategies. Prevalence of genomic alterations associated with intrinsic ICI resistance in TMB-high solid tumors. ICI resistance marker Prevalence in TMB-High Tumors STK11 2.4% KEAP1 0.3% PTEN 7.6% CTNNB1 2.6% APC 15.9% B2M 2.4% JAK1 0.2% JAK2 0.0% MDM2 2.5% MDM4 0.4%
Efficacy of venetoclax-based therapy in t(11;14)–positive relapsed/refractory multiple myeloma: A systematic review and meta-analysis.
e19570 Background: Translocation between chromosomes 11 and 14 [t(11;14)] is one of the most common primary cytogenetic abnormalities in multiple myeloma. Venetoclax is a highly selective, oral BH3 mimetic that binds B-cell lymphoma-2 (BCL-2), inducing apoptosis in BCL-2–dependent plasma cells. Early phase studies suggested promising activity of venetoclax-based regimens, particularly in t(11;14) relapsed/refractory multiple myeloma (RRMM). However, venetoclax has not received FDA approval for the treatment of RRMM, in part due to results from two phase III randomized trials. Methods: A systematic literature search was performed across PubMed-MEDLINE, Embase-OVID, CENTRAL, ClinicalTrials.gov, and Web of Science databases up to January 1, 2025. Randomized phase III trials evaluating venetoclax-based therapy versus standard-of-care regimens in patients with t(11;14)-positive RRMM were included. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and time to deterioration in disease-related symptoms (TTDDS) were secondary outcomes. Hazard ratios (HRs) were pooled using a random-effects inverse-variance model with heterogeneity assessed using the I² statistic. Results: A total of 298 patients from two phase III randomized controlled trials (CANOVA and BELLINI) were included. Venetoclax-based therapy was associated with a directionally favorable improvement in PFS (pooled HR 0.40; 95% CI, 0.08–1.91). No pooled OS benefit was observed (HR 1.15; 95% CI, 0.78–1.71). Venetoclax-based regimens demonstrated a trend toward prolonged TTDDS (TTDDS HR 0.70; 95% CI, 0.46–1.05). Substantial heterogeneity was observed for PFS (I² = 88.8%), while heterogeneity was minimal for OS and TTDDS (I² = 0%). None of the pooled efficacy outcomes reached statistical significance. Conclusions: Venetoclax-based therapy demonstrates a directionally favorable effect on PFS and TTDDS in t(11;14)-positive RRMM. In BELLINI, despite a small subgroup sample size, venetoclax demonstrated an effect size rarely observed in RRMM, whereas CANOVA was conducted against a highly active comparator. Future trials should prioritize t(11;14) populations and consider non-inferiority or combination-based comparator designs. The lack of statistical significance in pooled outcomes likely reflects differences in trial design and treatment backbone rather than absence of biological activity. Summary of outcomes. Study Venetoclax-Based Regimen Control Regimen PFS* HR(95% CI*) OS* HR(95% CI*) TTDDS* HR (95% CI*) CANOVA Venetoclax + Dexamethasone Pomalidomide + Dexamethasone 0.82(0.60–1.14) 1.19(0.80–1.77) 0.77(0.49–1.21) BELLINI Venetoclax + Bortezomib + Dexamethasone Placebo + Bortezomib + Dexamethasone 0.16(0.06–0.45) 0.35(0.03–3.84) 0.46(0.18–1.18) Pooled Estimates 0.40(0.08–1.91) 1.15(0.78–1.71) 0.70(0.46–1.05)
<i>MTAP</i> deletions and co-mutational landscape from whole genome sequencing in primary CNS tumors.
3117 Background: Biallelic deletions of the MTAP (methylthioadenosine phosphorylase) gene are frequent in solid tumors and confer synthetic lethality to PRMT5 (protein arginine methyltransferase 5) inhibition. Clinical trials are exploring the safety and efficacy of PRMT5 inhibitors (PRMT5i). Targeting additional co-occurring actionable alterations, such as gain-of-function mutations, with kinase inhibitors in combination with MTAP -directed synthetic lethality may potentiate therapeutic efficacy. MTAP deletions are present in up to 40% of glioblastomas (GBM) and occur sporadically in other primary central nervous system (CNS) tumors. Identification of actionable targets beyond MTAP deletions could enable combination strategies in these diagnoses, with otherwise limited therapeutic options. Whole-genome sequencing (WGS) with exon-level copy number alteration (CNA) analysis allows accurate determination of MTAP status, assessment of concordance with copy number variations (CNVs) in the neighboring CDKN2A and CDKN2B genes, and evaluation of the prevalence of co-occurring actionable alterations (including IDH1, KRAS, PIK3CA, FGFR, and NTRK alterations). Methods: A total of 145 consecutive patients with primary WHO grade 4 gliomas or other primary CNS tumors underwent WGS at the time of diagnosis as part of the prospective Neurogenome Study at Copenhagen University Hospital between January 2023 and October 2025. 57 patients (39%) were female, and the median age was 59 years (range, 26–78). MGMT promoter methylation was detected in 59 patients (40.4%); 6 tumors were not evaluable for MGMT status. 130 cases (GBM, n=118; astrocytoma, IDH -mutant, n=12) had reliable MTAP copy number analysis, samples with e.g. high fraction of normal tissue where excluded from analysis. Results: Among the 130 evaluable cases, 52 (40%) harbored biallelic MTAP deletions, 37 (28%) had monoallelic deletions, and 39 (30%) had no MTAP deletions. 2 cases (1.5%) had deletion of one MTAP allele with partial deletion of the second allele (exon-level deletions). Concordance between MTAP CNVs and CDKN2A/ B CNVs—defined as either biallelic deletion or non-biallelic deletion of both MTAP and CDKN2A/B genes—was observed in 113 of 130 cases (87%). 31 cases harbored additional potentially actionable alterations. In tumors with biallelic MTAP deletions, 9 cases contained co-occurring actionable targets ( FGFR fusion 1; KRAS mutation 1; NTRK fusion 1; PIK3CA mutation 4; IDH1 + PIKCA3 mutations 1; IDH1 mutation + PTPRZ1-MET fusion 1). Conclusions: MTAP biallelic deletions were frequent at diagnosis in this primary CNS tumor population, whereas partial deletions of the MTAP gene (exon deletions) were rare. High concordance with CDKN2A/B status on WGS was observed. A subset of cases with biallelic MTAP deletions harbored other actionable targets underscoring the potential for combining PRMT5i with other targeted agents.
HER2 expression in squamous cell carcinoma of the vulva: A systematic review and meta-analysis.
e17653 Background: Vulvar cancer is a rare gynecologic malignancy comprising 1–3% of all cases. No established standard exists for advanced disease. Recent activity of HER2-directed antibody–drug conjugates in solid tumors (ORR ~37%) highlights the need to better characterize HER2 expression in vulvar cancer. The aim of this study was to determine prevalence of HER2 expression in vulvar cancer through a systematic review and meta-analysis. Methods: We performed a systematic search of Medline, Embase, CENTRAL, and the Cochrane Database of Systematic Reviews from inception to May 2025. Eligible studies included ≥10 vulvar cancer cases with HER2 assessment by immunohistochemistry and/or in situ hybridization. Vulvar Paget’s was excluded. Two reviewers independently screened studies. A random-effects model was used to estimate pooled HER2-positivity. Heterogeneity was assessed using Cochran’s Q and Higgins’s I². Publication bias was explored with Egger's test. Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n=752) across 5 countries met inclusion criteria. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Lymph-node involvement was reported in six studies including 361 patients, where lymph node status was positive in 48% (n=173). Molecular profiling was limited. Among three studies with known TP53 status (n=206), 59% expressed TP53 (n=122), and among two studies with known human papillomavirus (HPV) status (n=128), 21% (n=27) were HPV positive. Six studies were American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)-compliant. Pooled HER2 expression across ASCO/CAP compliant studies was 2% (95%CI 1%, 3%) and for ASCO/CAP non-compliant studies was 21% (95% CI: 2%, 52%). The overall pooled estimated proportion of HER2 positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies with an I² value of 90.2% [95% CI: 84.1%; 93.9%], but no significant publication bias was observed (Egger’s test p = 0.364). HER2 positive status was associated with nodal involvement and presence of distant metastases (2 studies; n=73 patients), as well as with adenocarcinoma histology (1 study; n= 143 patients). HER2 expression was not associated with survival in three studies that reported clinical outcomes. Conclusions: HER2 positive expression in squamous cell carcinoma of the vulva appears uncommon but may be underestimated. Standardized assessment using contemporary ASCO/CAP criteria is needed to clarify the prevalence of HER2-low, ultra-low versus HER2-positive disease to inform potential use of HER2-targeted therapy among patients with vulvar cancer.
Adjuvant oxaliplatin plus S-1 versus docetaxel plus S-1 for stage III gastric cancer after D2 gastrectomy (DRAGON-Adjuvant): A multicenter, open-label, phase 3, randomized, non-inferiority study.
TPS4249 Background: Adjuvant therapy is the standard treatment for stage II-III gastric cancer patients after radical D2 gastrectomy. Neoadjuvant therapy has been demonstrated as an effective strategy for resectable gastric cancer patients, while less than 2% of patients received such treatment in China. Therefore, adjuvant chemotherapy following radical resection is still widely used in current clinical practices. For stage III gastric cancer patients, oxaliplatin or docetaxel combined with oral fluoropyrimidine as adjuvant regimens are recommended by clinical guidelines. Although historical data show comparable efficacy between these regimens, direct comparisons are not feasible due to differences in study design, enrolled populations, and treatment cycles. Regimen selection is mainly based on clinical experience, as high-level evidence is still lacking. Currently, minimal residual disease (MRD) detection based on ctDNA testing can indicate patient prognosis and adjuvant therapy selection in colorectal cancer. The role of ctDNA-based MRD detection in adjuvant therapy of gastric cancer is still under investigation. This study aims to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus docetaxel plus S-1 (DS) as adjuvant therapy for stage III gastric cancer, and to explore the role of MRD in adjuvant setting of gastric cancer. Methods: DRAGON-Adjuvant (NCT07366528) is a prospective, open-label, multicenter, randomized, non-inferiority study in patients aged from 18 to 80 years who are histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction, with pathological staging at AJCC stage IIIA to IIIC after standard D2 gastrectomy and R0 resection. Patients had no prior neoadjuvant therapy. Eligible patients will be randomized and assigned into experiment group (SOX, n = 193) and control group (DS, n = 194), respectively. Experiment group patients will be treated with eight 3-week cycles of intravenous oxaliplatin (130mg/m 2 on day 1 for each cycle) with orally S-1 on days 1 to 14 of a 3-week cycle. Control group patients will be treated with S-1 on days 1 to 14 of a 3-week cycle (C1), then intravenous infusion of docetaxel (40mg/m 2 ) on day 1 of each cycle and S-1 on days 1 to 14 of a 3-week cycle (C2 to 7), then S-1 continued on days 1 to 28 of 6-week cycles for up to 1 year. S-1 dose is dependent on body surface area. The primary objective is to assess that 3-year disease-free survival rate of SOX group is not inferior to DS group. Secondary objectives are to compare the 5-year overall survival rate, safety profiles, and recurrence sites in two groups. Exploratory objective is to assess the correlation of MRD with treatment efficacy and patient prognosis. As of January 2026, the DRAGON-Adjuvant is recruiting patients at 5 sites in China. Clinical trial information: NCT07366528 .
Serum VEGF-A concentrations as a predictive biomarker of immunotherapy response in refractory metastatic colorectal cancer (mCRC): An exploratory analysis of CCTG CO.26.
3547 Background: Benefits of immune checkpoint inhibitors (ICIs) in unselected proficient mismatch repair (pMMR) mCRC remain unestablished. This exploratory analysis of CCTG CO.26 evaluated whether serum VEGF-A concentrations may influence ICI efficacy. Methods: CCTG CO.26 was a phase II trial that randomized refractory mCRC patients (pts) (2:1) to Durvalumab + Tremelimumab + Best supportive care (DT) vs Best supportive care (BSC) alone and was positive for overall survival (OS). VEGF-A concentrations were determined in baseline serum samples using an ELISA method. OS and progression-free survival (PFS) were compared between high and low groups based on median VEGF-A concentration in each treatment arm. An optimal cutoff was also identified using a minimal p-value approach. VEGFA mRNA expression from tissue-based RNA-seq was analyzed in the INSPIRE study, a separate, single arm, multicohort phase II trial comprising multiple tumor types treated with pembrolizumab for external validation. Results: Baseline VEGF-A concentrations were available for 161 pts (47 BSC, 114 DT). Median VEGF-A concentration was 1166 pg/ml (range: 226 – 4898; IQR: 784-1755). VEGF-A concentrations were significantly higher in ECOG 1 vs 0 pts (p = 0.03), and in pts who had previously received regorafenib (p = 0.03). Grouped by median VEGF-A, median OS was longer in DT-treated patients with low VEGF-A (7.39 months for DT-Low vs. 6.08 DT-high; hazard ratio (HR) 0.62, 95% confidence interval (CI): [0.42–0.90], p = 0.01), but not in BSC treated patients (4.44 months BSC-Low vs. 4.11 BSC-High; HR 1.05 [0.57–1.92], p = 0.88; interaction HR 0.56 [0.28–1.14], p = 0.11). An optimal VEGF-A threshold of 1540 pg/mL was identified using a minimal p-value approach, with 33.5% pts having high VEGF-A concentrations. Median OS was 7.29 vs 4.37 months for DT-Low and DT-High pts (HR 0.53 [0.35–0.80], p < 0.005), and 3.55 vs 7.46 months for BSC-Low and BSC-High pts (HR 1.50 [0.80–2.80], p = 0.21; interaction HR 0.33, [0.16–0.70], p < 0.005). In multivariable analyses incorporating ECOG, presence of liver metastases, plasma tumor mutation burden and arginine levels, low VEGF-A concentrations remained statistically associated with improved OS with DT (HR 0.46 [0.30–0.70], p < 0.001; interaction HR 0.18 [0.083–0.41], p < 0.0001). There was no association between VEGF-A concentrations and PFS in any arm. In the INSPIRE study (n = 66), VEGFA mRNA expression was lower in responders (p < 0.001) and significantly associated with improved PFS (HR 0.45 [0.25–0.79], p = 0.006) and OS (HR 0.47 [0.26–0.85], p = 0.013) across tumor types. Conclusions: Refractory mCRC patients with low VEGF-A concentrations may derive benefit from ICIs. This is the first report to suggest that serum VEGF-A concentration is a potential predictive biomarker for benefit from ICIs. These findings should be prospectively validated.
Targeted bronchial washing fluid–based sequencing for detection of actionable genomic alterations in early-stage non–small cell lung cancer: A comparative analysis with plasma and surgical tissue.
e20056 Background: In early-stage non–small cell lung cancer (NSCLC), plasma-based liquid biopsy has limited sensitivity due to low circulating tumor DNA shedding. This study evaluated the performance of targeted bronchial washing fluid (TBWF) as a tumor-proximal source for genomic profiling. Methods: This prospective observational study enrolled patients with clinical stage I–IIIA NSCLC undergoing diagnostic bronchoscopy followed by curative-intent surgical resection. Next-generation sequencing (NGS) was performed on TBWF, plasma, and matched surgical tissue specimens. The primary outcome was the detection rate of actionable genomic alterations (GAs) across specimen types. Secondary outcomes included concordance, co-occurring GAs, and procedural safety. Results: Among 52 patients with successful triplet NGS results, at least one actionable GA was identified in 79%. TBWF-based NGS detected actionable GAs in 69.2%, comparable to surgical tissue (71.2%; P = 0.830) and significantly higher than plasma (6%; P < .001). Concordance between TBWF and tissue was 83%, whereas concordance involving plasma was markedly lower. Across stages I–III, TBWF maintained detection rates comparable to tissue, while plasma showed marked stage dependence. Co-occurring GAs were detected more frequently in tissue (69%) than TBWF (44%). Targeted bronchial washing was safe, with only mild self-limited bleeding reported (17%). Conclusions: TBWF-based NGS provides reliable detection of actionable GAs in early-stage NSCLC, showing performance comparable to surgical tissue and clearly superior to plasma. TBWF may complement genomic profiling, particularly when preoperative tissue is limited.
Patterns in place of death amongst Black women with breast cancer: A retrospective study.
e13741 Background: Breast cancer remains a leading cause of cancer-related mortality amongst Black women, who experience disproportionately higher mortality rates compared to other racial groups. Structural inequities, delayed diagnoses, differences in treatment access, and socioeconomic barriers contribute to these disparities. Despite the high burden of breast cancer in the Black community, limited research has examined end-of-life outcomes, particularly the patterns in the place of death. Understanding where Black women with breast cancer die can provide insight into healthcare access, utilization of palliative services, and regional disparities in care. This study investigates trends in the place of death amongst Black women with breast cancer in the United States from 1999-2020. Methods: A retrospective analysis was conducted using data from the CDC WONDER database, examining death certificates listing breast-cancer-related deaths (ICD-10 codes C50.0-C50.9) in Black women from 1999-2020. Demographic factors including year, age, and urbanization status were examined with respect to the place of death. The number and percentage of deaths occurring in various locations were tracked to identify patterns and trends. Results: 151,734 deaths were attributed to breast cancer in Black women from 1999 to 2020. The majority occurred in inpatient settings (39.5%), followed by deaths at home (30.9%). Temporally, home deaths in 2020 approached a two-fold increase compared to 1999. In addition, deaths in nursing homes/long-term care facilities rose progressively with advancing patient age, peaking in women aged 85 years and above. Comparing across urbanization statuses, Black women in urban settings were nearly twice as likely to die in hospice compared to women in rural settings (7.7% vs 4%). Regionally, the South and Midwest census regions recorded the highest burdens. Conclusions: Distinct and evolving patterns in place of death are observed among Black women with breast cancer, with significant variation by age, time period, and urbanization status. The increasing shift toward home deaths over time suggests gradual improvement in end-of-life care utilization; however, the persistently high proportion of inpatient deaths and the rising burden of nursing facility deaths among older women underscore ongoing gaps in timely palliative care integration. Marked rural–urban disparities in hospice deaths further highlight structural inequities in access to end-of-life services. Targeted efforts to expand equitable hospice availability, promote earlier palliative care referral, and address geographic barriers are essential to improving patient-centered end-of-life care for Black women with breast cancer.
Updated two-year overall survival and toxicity outcomes of BCMA CAR-T therapy compared with teclistamab in multiple myeloma.
7527 Background: B-cell maturation antigen (BCMA) targeted chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies have transformed the treatment landscape for relapsed or refractory multiple myeloma. In a prior real-world study, CAR-T therapy was associated with improved short-term overall survival compared with teclistamab; however, follow-up was limited to less than one year. Longer-term comparative outcomes between these modalities remain insufficiently characterized. This sequel study evaluates the updated two-year overall survival and toxicity outcomes. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, comprising data from over 70 healthcare institutions in the United States, to identify patients with multiple myeloma treated between 2021 and 2023 with either CAR-T therapy (ciltacabtagene autoleucel [cilta-cel] or idecabtagene vicleucel [ide-cel]) or teclistamab. Patients who received other bispecific antibodies, including elranatamab, talquetamab, or linvoseltamab, were excluded. Two mutually exclusive cohorts were defined: patients who received CAR-T therapy without prior or subsequent teclistamab and patients who received teclistamab without prior or subsequent CAR-T therapy. Propensity score matching was performed to balance baseline demographics, comorbidities, prior therapies, and laboratory values. HR and 95% CI were estimated using Cox proportional hazards models for two-year overall survival, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Results: A total of 351 CAR-T cell therapy recipients and 507 teclistamab recipients were included. After propensity score matching, 227 patients were retained in each cohort, with well-balanced baseline characteristics, including demographics (mean age: 65 years, White: 74%, male: 53%), comorbidities, and prior multiple myeloma treatments, including immunomodulatory drugs, proteasome inhibitors, dexamethasone, and anti-CD38 antibodies. Mean follow-up durations were comparable between the CAR-T and teclistamab cohorts at 524 and 438 days, respectively. CAR-T therapy was associated with significantly improved two-year overall survival compared with teclistamab (HR: 0.61, 95% CI: 0.43-0.87, p=0.005). In contrast, CAR-T therapy was associated with higher risks of CRS (HR: 1.48, 95% CI: 1.12-1.96, p=0.003) and ICANS (HR: 2.02, 95% CI: 1.20-3.41, p=0.007). Conclusions: In this extended two-year real-world analysis, CAR-T therapy was associated with superior overall survival compared with teclistamab, albeit with increased immune-mediated toxicities. These findings build upon prior short-term data and underscore the need for prospective studies directly comparing BCMA-targeted treatment strategies across longer follow-up intervals.
Predictive value of ctDNA-based MRD combined with PET-CT and gastroscopy for treatment efficacy in locally advanced esophageal squamous cell carcinoma: A phase II exploratory clinical trial.
e16119 Background: Based on the SANO trial establishing active surveillance non-inferiority after clinical complete response (cCR) in oesophageal cancer, and prior evidence of prognostic value of ctDNA (circulating tumor DNA) in locally advanced esophageal squamous cell carcinoma (ESCC), this phase II exploratory trial aims to evaluate the combined predictive value of ctDNA, PET-CT, and gastroscopy for treatment efficacy in cCR patients after neoadjuvant therapy. Methods: Patients (pts) with locally advanced or oligometastatic ESCC (cT1-4a N+ M0/M1 [limited to supraclavicular lymph node metastasis only]) were enrolled. Treatment comprised induction chemotherapy (albumin-bound paclitaxel/cisplatin/capecitabine, 3 cycles) followed by concurrent radiotherapy (50 Gy) with 2 cycles of anlotinib (10 mg, p.o., qd, d1-14, q3w) and camrelizumab (200 mg, iv, d1, q3w). Post-treatment response was assessed at 4-6 weeks. A post-radiotherapy surveillance regimen integrating ctDNA-based MRD (minimal residual disease) detection, PET-CT, and gastroscopy was implemented. Patients with no evidence of disease (negative for MRD [M], PET-CT [P], and gastroscopy [G]) were classified as MPGN. Any positive finding among these three modalities were classified as MPGP. Subsequent surgery considered residual disease and patient preference. The primary endpoint was the 2-year event-free survival (EFS) rate. Secondary endpoints included pathological complete response (pCR) rate, 2-year overall survival (OS) rate, and safety. Results: As of January 14, 2026, 40 pts were enrolled (median age 63 years). Stage distribution: 47.5% III, 25.0% IVA, 20.0% IVB. After a median follow-up of 17.5 months (IQR: 11.2, 33.5), the 2-year EFS rate was 55.6% (95% CI, 38.9-79.3), with a median EFS of 34.9 months (95% CI: 21.1-NA). Of the 16 patients (40.0%) undergoing radical surgery post-neoadjuvant therapy, pCR and R0 rates were 43.8% (95% CI: 19.8-70.1) and 93.8% (95% CI: 69.8-99.8), respectively. A primary tumor ΔSUVmax reduction of ≥65% post-radiotherapy correlated with improved EFS (p = 0.0052) and OS (p = 0.0050). Patients were classified as MPGN (n = 9) or MPGP (n = 28). The 2-year EFS rate was 85.7% (95% CI: 63.3-100.0) in MPGN vs. 47.1% (95% CI: 27.3-81.1) in MPGP; 2-year OS rate was 100.0% vs. 62.1% (95% CI: 42.3-91.3), respectively. Any-grade TEAEs occurred in 92.5% of patients, most commonly esophagitis (70.0%), odynophagia (60.0%), leukopenia (32.5%), and fatigue (22.5%). Conclusions: Integrated post-treatment assessment using ctDNA-based MRD, PET-CT, and endoscopy shows predictive potential for survival in locally advanced ESCC following induction chemotherapy and concurrent radiotherapy with anlotinib and camrelizumab. These results require prospective validation in larger cohorts with longer follow-up. Clinical trial information: ChiCTR2200056920.
Clinical outcomes of patients with PI3K pathway alterations by treatment type: The MD Anderson Cancer Center IMPACT 2 study.
3150 Background: The phosphatidylinositol 3-kinase (PI3K) pathway regulates cell growth, metabolism, and survival and is involved in immune modulation. Alterations in PI3K signaling drive tumor progression and drug resistance in advanced cancers and are associated with poorer prognosis. Herein, we report the clinical outcomes of patients with PI3K pathway alterations treated in the IMPACT 2 study (2014-2023; NCT02152254). Methods: Patients with advanced cancer underwent tumor biopsy and molecular profiling (CLIA-certified lab). Pathway analysis was conducted using the maftools R package. PI3K pathway alterations were defined as those involving the PI3K, AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2 genes. Cases were discussed at Molecular Tumor Board meetings. Patients were treated on clinical trials with investigational agents that included matched targeted therapies (MTTs) when available. We analyzed the following outcomes by treatment type (MTT vs. non-matched targeted therapy [NTT] and immunotherapy [IO] vs. non-IO): objective response rate (ORR; complete response + partial response), clinical benefit rate (CBR; ORR + stable disease ≥4 months), progression-free survival (PFS), and overall survival (OS). Results: Of 491 treated patients with targetable alterations, 133 (27.1%) had PI3K pathway alterations (median age, 60.3 years [range, 20.5-79.8]; female, 60.9%; ECOG performance status 1, 85.7%; median number of prior therapies, 3 [range, 0-14]; liver metastases, 42.9%; >2 metastatic sites, 44.3%; high lactate dehydrogenase levels, 42.1%; low albumin level, 9%). The most common tumor types were breast cancer (18%), colorectal cancer (15%), and sarcoma (12%). Concomitant pathway alterations were TP53 (49.6% of patients), RTK/RAS (43.6%), and cell cycle (35.3%). Other tumor characteristics included PD-L1≥1%, 40.5% (32/79); MSI-H, 2.2% (2/89); and TMB-H, 10.3% (9/87). MTT included mTOR inhibitors, n=17; AKT inhibitors, n=5, and PI3K inhibitors, n=4. Clinical outcomes are shown in the Table. Conclusions: Taking into consideration the relatively limited use of AKT and PI3K inhibitors compared with mTOR inhibitors, no differences were noted in tumor response, PFS, or OS, by type of treatment. Other contributing factors may include the biological complexity of targeting this pathway, the small number of patients and/or the limited availability and antitumor activity of MTTs. Clinical trial information: NCT02152254 . All patients MTT NTT P IO Non-IO P N = 133 N=26 N=107 N=35 N=98 ORR (%) 9/112 (8.0) 1/23 (4.3) 8/89 (9.0) 0.68 4/32 (12.5) 5/80 (6.3) 0.51 CBR (%) 63/112 (56.3) 15/23 (65.2) 48/89 (53.9) 0.36 18/32 (56.3) 45/80 (56.3) 1.00 Median PFS, months(95% CI) 2.96(2.27, 4.57) 4.08(2.17, NA) 2.66(2.1, 4.37) 0.36 4.14(1.84, 9.86) 2.96(2.24, 4.37) 0.31 Median OS, months(95% CI) 7.79(6.54, 10.92) 9.04 (6.64, 14.99) 7.3 (5.59, 11.21) 0.64 8.75(5.36, 25.55) 7.17(6.18, 0.78) 0.40
Sequencing trastuzumab deruxtecan and sacituzumab govitecan in metastatic breast cancer: A systematic review and meta-analysis.
e13074 Background: Antibody–drug conjugates (ADCs) have significantly improved outcomes in metastatic breast cancer (mBC), including tumors with HER2-low expression. Trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) are both approved across diverse mBC subtypes; however, no standard sequencing strategy exists for patients eligible for both agents. This systematic review and meta-analysis aimed to evaluate the clinical efficacy of T-DXd and SG used sequentially in patients with mBC in order to identify the sequencing patterns associated with improved progression-free survival (PFS) and, secondarily, overall survival (OS). Methods: A systematic literature research was conducted in December 2025 using PUBMED/MEDLINE, Scopus and Cochrane databases with additional searches of recent conferences. Prospective and retrospective clinical studies of patients receiving sequentially both ADCs, reporting PFS of the second and/or the first ADC were eligible. Published Kaplan–Meier curves were digitized to reconstruct pseudo–individual patient–level data. Outcomes of interest included PFS, following the first (PFS1) and second (PFS2) ADC, each defined as the time from initiation of the respective treatment until disease progression. Hazard ratios (HRs) were calculated for each study and pooled using fixed- and random-effects meta-analytic models. Study heterogeneity was assessed using the I² statistic. Sensitivity analyses were performed when required and feasible. Results: The literature search yielded 694 records; following duplicate removal and eligibility assessment, 17 studies were included in the final analysis. Seven studies including 474 patients were included in the PFS2 analysis (SG→T-DXd, n = 246; T-DXd→SG, n = 228). Median PFS2 was 3.3 months (95% CI: 2.9–3.7) for SG→T-DXd and 2.8 months (95% CI: 2.9–3.7) for T-DXd→SG (p = 0.008). The pooled fixed-effects HR favored SG→T-DXd (HR 1.49; 95% CI: 1.22–1.83), which was confirmed using a random-effects model (HR 1.72; 95% CI: 1.10–2.68), despite substantial heterogeneity (I² = 70.9%). Sensitivity analysis excluding one study reduced heterogeneity (I² = 0%) and yielded a pooled HR of 1.9. Conclusions: In previously treated mBC, sequencing T-DXd after SG was associated with improved PFS2 compared to the reverse sequence. These findings warrant further investigation on the optimal ADC sequence, but also underscore the need for predictive biomarkers to optimize treatment selection in each patient with mBC.
Impact of fertility concerns on endocrine therapy.
631 Background: Adolescent and young adult (AYA) women with breast cancer who have not completed their desired childbearing pre-diagnosis may be more likely to decline adjuvant endocrine therapy (ET) and/or to temporarily or permanently stop ET to pursue pregnancy. Fertility counseling and use of fertility preservation strategies (e.g., oocyte/embryo cryopreservation) might impact these decisions. Methods: In the Valuing Opinions and Insights from Cancer Experiences (VOICE) Study, we investigated whether use of fertility preservation strategies were associated with ET initiation and early discontinuation amongst AYAs with fertility concerns. Eligible females were diagnosed with stage 1–3 estrogen-receptor positive breast cancer at age 15-39 during 2013-2022 and responded to a survey in 2023-2024. Those who reported that they had not completed their desired family size or had been unsure about having completed their desired family size at the time of their cancer diagnosis were categorized as having had fertility concerns. ET initiation was defined as 2+ ET prescription fills within 18 months after diagnosis. Among ET initiators, we assessed early discontinuation (defined as lack of ET prescription fill over any 180 day period until 5 years after their first ET fill date). Due to inadequate power, we did not model the relationship between oocyte/embryo cryopreservation and ET initiation. However, we did have power to assess the association between oocyte/embryo cryopreservation and ET discontinuation using multivariable Cox regression to calculate Hazard Ratios (HR) and 95% Confidence Intervals (CI). HRs for discontinuation were adjusted for age at diagnosis, stage, study site, diagnosis year, income, and children before diagnosis (yes/no). Results: Among 518 AYA breast cancer survivors, 56% (N = 290) had fertility concerns at diagnosis. Of these 290, 41% had 1+ child before diagnosis, 90% received fertility counseling, 27% froze eggs or embryos, and 10% had 1+ child after diagnosis. The majority (89%) initiated ET. Among the 32 who did not initiate ET, 7 (22%) reported that fertility concerns impacted that decision. Oocyte/embryo cryopreservation was used by 26% of ET initiators and 34% of ET non-initiators. Among the 258 ET initiators, 89 (35%) discontinued ET early. Compared to those who did not use fertility preservation strategies, patients who froze oocytes/embryos were more likely to discontinue ET (HR 1.89; 95% CI 1.18–3.05). Among those who discontinued ET, 19% had 1+ child after diagnosis (compared to 2% among those who did not discontinue ET). Conclusions: This study confirmed prior studies showing that many AYAs with breast cancer have fertility concerns, and these concerns may impact decisions about ET. In our analysis, those who cryopreserved oocytes/embryos were more likely to discontinue ET early, and a higher proportion who discontinued ET had 1+ live birth after breast cancer.
Spectrum of germline pathogenic and novel BRCA1 and BRCA2 gene mutations in a cohort of 1780 breast and ovarian carcinoma patients from east India.
10614 Background: Advances in our understanding of the molecular basis of cancer have pushed us in a new era of personalized medicine in oncology. The adoption of personalized medicine in Breast cancer (BC) and Ovarian cancer (OC) care holds significant promise. Homologous recombination repair (HRR) process aids in the restoration of halted replication forks during DNA replication. Where, an effective HRR depends on the normal functioning of oncoproteins, BRCA1 and BRCA2 playing crucial roles. Methods: Germline Next Generation Sequencing based BRCA1 & BRCA2 gene panel on ion torrent technology was employed in 1780 diagnosed BC and OC patients for genetic-molecular evaluation. Bioinformatics pipelining and data analysis was performed as per Ion Reporter pre-designed stringent workflows for germline variant screening. Variants were called as per ACMG guidelines and framework. Results: A total of 993 (55.8%) BC, 673 (37.8%) OC and 114 (6.4%) patients with co-existing BC & OC participated in the study. Out of which, 232 (13%) patients were found to harbour a clinically significant BRCA1 or BRCA2 gene variant. Predominantly, BRCA1 was the most mutated gene (68%; n = 158), followed by BRCA2 (32%; n = 74) across cohort. 48.2% of BRCA variants were noted in BC while 41.7% in OC and 10.1% in co-existing BC & OC patients respectively. Majority of the pathogenic variants (55.4%) were detected in high-grade tumors with mean age of 45.2 years. Exon-10 (33.3%) of BRCA1 and exon-11 (47.2%) of BRCA2 genes were the most mutated regions detected. Additionally, findings revealed 21 (9.1%) novel (14 in BRCA1 and 07 in BRCA2 genes) variants across BRCA genes not reported previously in ClinVar (NCBI) or BIC (Breast Information Core) databases. BRCA1 gene, exon-02, c.68_69del (185delAG) was the most pre-dominant (10.3%) variant in the patient cohort. Conclusions: India has emerged as the global cancer capital with BC being the most incidental cancer in women. Investigating the BRCA1, BRCA2 gene status in the current patient cohort has enabled the identification of not only the recurring hotspot pathogenic variants but also novel variants, as per the NCCN guidelines with actionable targets. Among BC, elevated and alarming frequency of TNBC patients (37.5%) was noted. The study findings provide a wide spectrum of BRCA gene variants specific to East-Indian patients with novel gene mutations pertaining to Indian population. These findings support the development of targeted therapeutic strategies by enabling the alignment of individual patients with treatments most likely to confer clinical benefit. Such precision oncology approaches may improve therapeutic efficacy, minimize treatment related toxicity, and ultimately enhance quality of life among cancer patients. Keywords: Breast & Ovarian cancer; BRCA1; BRCA2; NGS; Precision therapeutics.
Electrolyte Covalent Organic Frameworks for Exceptional Potassium Ion Conduction
ABSTRACT In this research we report the concept and strategy of electrolyte covalent organic frameworks for high‐rate low‐activation‐energy potassium ion conduction. One‐pot polymerization of monomers with oligo(ethylene oxide) chains of different lengths creates crystalline porous electrolyte frameworks with discrete electrolyte interfaces in pores. Integration of potassium salts to the pores develops potassium ion‐electrolyte networks, offering pathways for potassium ion transport. Notably, the frameworks with well‐developed electrolyte interfaces improve ion conductivity, which is not a simple numeric summation of electrolyte chains but shows an exponential correlation. The materials operate over temperatures from 40°C to 190°C under anhydrous conditions and achieve an ion conductivity as high as 3.2 × 10 −3 S cm −1 with a low activation energy of 0.2 eV. Notably, under humid conditions, the conductivity further increases to 2.1 × 10 −1 S cm −1 with an activation energy of only 0.04 eV, suggesting a frictionless ion conduction. Remarkably, potassium ion batteries show a stable and wide voltage window of –6 – 6 V, with a high potassium ion transference number of 0.76. Our results pave a way to exceptional potassium ion conduction through molecular design of electrolyte frameworks and show their promise for various types of energy storages under solid‐state and aqueous conditions.