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Mapping the association between federal AI investment and clinical validation in oncology: A multi-source ecosystem analysis.
Vinh, Tuan, Zhang, Julie Ying, Anand, Anvi, Pham, Huy, Sun, Chenyu

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e13663 Get It

e13663 Background: Artificial intelligence (AI) in oncology, including computer vision and radiomics, has expanded rapidly with substantial federal support. However, the extent to which growth in funding and publications is accompanied by growth in prospective interventional evaluation is not well quantified. We conducted an ecosystem-level analysis to compare temporal trends in federal awards, peer-reviewed publications, and interventional clinical trial registrations in AI-oncology. Methods: We performed a cross-sectional landscape analysis spanning 2015–2025 using three public data sources: (1) federally funded extramural awards indexed in NIH RePORTER (including NIH/NCI and other agencies where available); (2) interventional studies registered on ClinicalTrials.gov; and (3) PubMed-indexed publications. Records were identified using a consistent Boolean query requiring AI-related terms (“artificial intelligence,” “machine learning,” “deep learning,” “neural network,” “large language model,” “computer vision,” “natural language processing,” “radiomics”) AND oncology-related terms (“cancer,” “oncology,” “tumor,” “neoplasm,” “carcinoma,” “melanoma,” “leukemia,” “lymphoma”). Annual absolute counts were extracted (without normalization) to preserve volume differences across the ecosystem. We summarized growth over time and calculated publication-to-trial and grant-to-output ratios. Results: Between 2015 and 2025, AI-oncology federal awards totaled 11,503. PubMed-indexed AI-oncology publications increased 38-fold from 558 (2015) to 21,414 (2025), totaling 81,782. Interventional AI-oncology trial registrations increased from 2 (2015) to 84 (2025), totaling 372 across the period. Overall, the publication-to-interventional-trial ratio was 220:1; interventional trial registrations represented 0.45% of publication volume. For every federal award, approximately 7 publications were produced, but only 0.03 interventional trials were registered. Conclusions: Across 2015–2025, AI-oncology funding and publications increased dramatically, while interventional trial registrations remained comparatively sparse. This persistent publication-to-trial gap highlights a translational bottleneck and supports targeted initiatives to accelerate prospective validation, such as dedicated funding mechanisms, multi-center evaluation networks, and trial-ready implementation infrastructure, to realize clinical benefit from AI in cancer care.
Neutrophil counts as a prognostic biomarker following breast cancer surgery: Insights from a Mayo Clinic platform study.
Liu, Li , Billstein, Laura , Vinh, Tuan, Zhang, Julie Ying, Fickel, Abigail, Du, Kaili , Lees, Elizabeth , Sun, Chenyu

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e12691 Get It

e12691 Background: Breast cancer prognosis is influenced not only by tumor-specific factors but also by systemic inflammatory responses. Elevated circulating neutrophils after surgery may reflect one such systemic inflammatory response that promotes a pro-tumorigenic environment. Neutrophil extracellular traps (NETs) have been recognized as promoters of cancer activity. However, there have been no studies looking at neutrophil count alone as an independent inflammatory marker in cancer. Clinical prognostic significance of post-operative neutrophil counts remains incompletely understood. If proven significant, neutrophil count is a simple, widely available measure to predict post-operative outcomes in patients with breast cancer. Methods: Data from the Mayo Clinic Platform were retrospectively analyzed, including only breast cancer patients with normal BMI and neutrophil counts recorded within one week after breast surgery. Patients who underwent radical mastectomy were excluded. Patients were stratified into two groups based on neutrophil count: high (>7×10⁹/L) and normal (1.7–7×10⁹/L). Clinical outcomes assessed included age distribution and 5-year overall survival. Age differences were evaluated using Cohen’s D, and Kaplan-Meier survival curves and hazard ratio estimation were performed using the Mayo Clinic Platform's tool. Results: A total of 899 patients were included in the study cohort: 303 in the high neutrophil group (Cohort A) and 596 in the normal neutrophil group (Cohort B). Age distributions were comparable between groups (Cohort A mean 59.2 ± 13.1 years; Cohort B mean 59.1 ± 14.3 years; Cohen's d = 0.0079). High neutrophil counts were significantly associated with reduced 5-year survival (77.8% vs. 84.5%) and an increased risk of mortality (HR 1.63; 95% CI: 1.16–2.29; P = 0.0041). Conclusions: Recent literature supports that surgery-induced NET formation may drive metastatic progression. Findings from this retrospective analysis at Mayo Clinic suggest that elevated neutrophil counts after breast cancer surgery are associated with poorer survival and may reflect systemic inflammation. While markers like NLR and NPAR have prognostic value, neutrophil count alone is a practical, accessible biomarker for clinical use. Limitations of this study include potential confounding factors such as lifestyle and comorbidities, and lack of subgroup analysis by breast cancer type, stage, and other treatments in addition to surgery. Further prospective studies are still needed for validation. Five-year survival rate comparison. Statistic High Neutrophil counts Normal Neutrophil counts Patient Count 303 596 1 Month Survival 99% 99.8% 5 Month Survival 97% 99.3% 10 Month Survival 94.4% 97.3% 30 Month Survival 85.4% 91.9% 60 Month Survival 77.8% 84.5% Hazard Ratio* 1.63 (95% CI: 1.16–2.29) P = 0.0041.
Staffing, accepted indications, and dose of Phase II cardiac rehabilitation: country income class and time-based comparisons from the International Council of Cardiovascular Prevention and Rehabilitation’s (ICCPR) 2025 Audit Update
Mampuya, Warner , Jiandani, Mariya P , Mbau, Lilian, Rivero, Monserrat Cruz , Anchique, Claudia V. , 丁荣晶 , Schalkwijk, Dinah L. van , Gallagher, Jonathan , Fernández, Rosalia, Maskhulia, L , Martinez, Jimena, Botha, Noel V Hau, Champaiboon, Jirapa , Yokoyama, Miho, Investigators, ICCPR Global Cardiac Rehabilitation Audit Update, Akinci, Buket, Carson, Rachael Pamela, Quesada-Chaves, Daniel F, Norekvål, Tone M, Kouidi, Evangelia , Таргыновна, Аймакова Гульсим, Quito, Benjamin Jose, Lima de Melo Ghisi, Gabriela , Turk-Adawi, Karam , Mampuya, Warner M , Jiandani, Mariya P , Mbau, Lilian , Cruz Rivero, Monserrat , Anchique, Claudia V , Gallagher, Jonathan , Gaye, Ngone Diaba , Kim, Won-Seok , Seron, Pamela , Maskhulia, Lela , Batalik, Ladislav , Chen, Ssu-Yuan , Supervía, Marta , Champaiboon, Jirapa , Grace, Sherry L , Mettananda, Chamila Dinushi Kukulege , Baťalík, Ladislav , Yokoyama, Miho Nishitani , Grace, Sherry L. , Akıncı, Buket , Candelaria, Dion , Quesada-Chaves, Daniel, Norekvål, Tone M. , Szadkowska, Iwona , Jug, Borut , Aimakova, Gulsim T., Radi, Basuni

European Journal of Preventive Cardiology | May 28, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/eurjpc/zwag292 | PMID 42207983 Get It

Abstract Aims To characterize global variation in cardiac rehabilitation (CR) staffing, indications, and prescribed dose by country income classification and compare findings with the International Council of Cardiovascular Prevention and Rehabilitation’s 2016 Global Audit. Methods and results Cross-sectional REDCap survey of Phase II/post-discharge CR programmes (May–September 2025). Outcomes were multidisciplinary team size/composition, accepted cardiac and non-cardiac indications, and centre-based CR dose. Comparisons were made across World Bank country income classifications and Audit decade (2016 vs. 2025). Of 7025 programmes identified globally, 1505 (median programme response rate = 62%/country) initiated a survey, from 90/113 (80%) countries with CR. CR was delivered by a multidisciplinary team of 7 (median; P25–P75 = 5–8; nurses, physiotherapists, cardiologists, and dietitians most common); teams were smaller in low-income countries (median = 4; P < 0.001), and physician specialty varied. Non-low-income programmes consistently accepted (≥90%) patients with acute coronary syndrome, with programmes in low-income countries less often accepting related interventions (e.g. surgery: low-income 0% vs. high-income 97%; P < 0.01), but non-cardiac indications were more frequently accepted (e.g. primary prevention, diabetes, and lung disease). Acceptance of heart failure increased compared with the previous Audit (70% vs. 87%; P < 0.001). Centre-based programmes prescribed a median of 20 h (P25–P75 = 12–30), typically two sessions/week over 8 weeks. Globally, 65 (72%) countries prescribed a median ≥12 sessions/programme. Programmes in upper-middle-income countries prescribed more sessions (median = 24, P25–P75 = 12–36; P < 0.001). Dose did not differ meaningfully between Audits (P = 0.07). Conclusion CR programmes globally are offered by small, but multidisciplinary teams. They accept guideline-indicated patients, with applicable variation by context. Insufficient dose in one-quarter of countries underscores investment need.
Understanding the impact of gold and silver signals on ERAS applications: A survey of hematology/oncology fellowship program directors.
Miller-Chism, Courtney N. , Close, Julia , Bazhenova, Lyudmila, Katzel, Jed A., Patel, Reema , Tawagi, Karine, Riffon, Mark, Prather, Abbey, Bazhenova, Lyudmila , Katzel, Jed Abraham , Riffon, Mark, Rothe, Michael, Manochakian, Rami

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 9007-9007

10.1200/jco.2026.44.16_suppl.9007 Get It

9007 Background: Since transition to virtual interviews, application and interview inflation have increased the work burden of GME recruitment. In 2021, AAMC ERAS implemented a process that allows applicants to assign signals to top programs of interest. There is a paucity of guidance on optimal use of ERAS signals (ES), resulting in apprehension and uncertainty amongst applicants and program directors (PD). For the 2026 ERAS cycle, Hematology/Oncology programs (HOP) had the option to participate in ES, in which applicants are provided 5 gold (G) signals and 15 silver (S) signals. First-hand knowledge on how ES was utilized by HOP, as well as PD perceptions about ES, may guide best practices on ES. Methods: During the ASCO Oncology Training Program Leadership Retreat in November 2025, an anonymous survey, assessing HOP utilization and perception of ES, and the impact of ES on recruitment practices, was launched. One PD from each HOP was invited to complete the survey while onsite. Results: 88 HOP (46% of ACGME HOP) are represented. 97% (n=85) utilized ES. Of HOP who used ES, 74% are academic. 32% are small (1-9 fellows), 43% medium (10-19 fellows), and 25% large (20+ fellows). 79% received 400+ applications. 69% reviewed applications without signals but gave higher consideration to signaled applicants. 25% only reviewed applications with signals. 28% used ES when creating rank list; 45% think ES utilization is appropriate during ranking. 85% reported ES did not alter their approach to applicants requiring visa sponsorship. 78% felt ES made the interview selection process easier. 66% were more satisfied with this year’s recruitment process compared to years without ES. The most requested change to ES was reduction of allowed signals, especially silver. 98% will use ES next year. Conclusions: Despite limited knowledge on ES impact on recruitment, nearly all surveyed HOP participated in ES this past year and will continue. Most HOP view ES positively though many desire changes, particularly with the number of signals. Most HOP consider all applications regardless of ES. However, some HOP with larger applicant pool are using ES as inclusion criteria for interview consideration. Signals are a strong predictor for interview invitation when internal selection criteria are met. The “borderline” applicant may be the greatest benefactor from ES, viewed similarly to the non-signaled applicant who meets internal selection criteria. Sharing PD perspectives and real-life data from this year’s ES process breeds opportunities for further improvement and increased confidence with ES. Likelihood HOP offer interview invitation based on quality of application and signals (%, n=85). Internal Selection Criteria Signal Extremely Likely Likely Neutral Unlikely Extremely Unlikely Met G 73 22 5 0 0 S 42 47 8 2 1 None 8 27 24 22 19 Nearly met G 4 35 39 19 3 S 0 9 52 28 11 Not met G 0 2 12 41 45 S 1 1 6 30 62
Initial safety and efficacy of A2B694, a logic-gated mesothelin (MSLN)–targeted Tmod chimeric antigen receptor T-cell (CAR T) therapy in patients with advanced solid tumors with HLA-A*02 loss of heterozygosity (LOH).
Molina, Julian R. , Ward, Jeffrey, Hecht, J. Randolph, Kirtane, Kedar, Marar, Rosalyn, Fankuchen, Olivia Rose, Mitchell, Jasmine, Maloney, David G. , Patel, Sandip Pravin , Dorigo, Oliver, He, Kai, Lou, Yanyan, Kundranda, Madappa N. , Xuan, Jacqueline D., Avila, Monica , Ward, Jeffrey, Kirtane, Kedar , Fankuchen, Olivia , Mitchell, Jasmine , Maus, Marcela V , Eng, Cathy , Hazim, Antonious , Dorigo, Oliver , Vu, Peter , Punekar, Salman R.

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 8579-8579

10.1200/jco.2026.44.16_suppl.8579 Get It

8579 Background: LOH may provide a means to target tumor versus normal cells, to augment the efficacy and safety of MSLN-targeted programs (Hecht et al. JCO . 2022). A2B694 is an autologous, logic-gated, Tmod CAR T therapy designed to improve tumor selectivity and decrease toxicity by integrating an MSLN CAR activator with an HLA-A*02 blocker (Hamburger et al. Mol Imm. 2020). Methods: The first-in-human, open-label, phase 1/2 EVEREST-2 (NCT06051695) study of A2B694 in patients with recurrent/metastatic MSLN-expressing cancers with tumor-associated HLA-A*02 LOH. The prescreening study BASECAMP-1 (NCT04981119) identifies eligible patients and cryopreserves leukapheresis product. Upon progression, A2B694 is manufactured and administered after lymphodepletion. Phase 1 primary objective: evaluate the safety and tolerability of A2B694 and identify a recommended phase 2 dose. Results: As of 05 January 2026, 13 patients were enrolled: 8 women/5 men, median age 59 years, 11 non-Hispanic White/2 Hispanic with unknown race. Tumor types included colorectal (n = 4), ovarian (n = 3), pancreatic (n = 3), non–small cell lung adenocarcinoma (NSCLC), gastro-esophageal, and mesothelioma (n = 1 each). A2B694 dose level (DL) groups were: DL1: 1×10 8 cells (n = 3), DL2: 2×10 8 cells (n = 4), DL3: 4×10 8 cells (n = 5), and DL4: 6×10 8 cells plus low-dose IL-2 (n = 1). Lymphodepletion prior to administration of A2B694 was well-tolerated, with expected, transient cytopenias. The only adverse event reported in more than 1 patient was grade 3 neutropenia. One patient had grade 3 ICANS and 1 patient had grade 1 CRS. There were no dose-limiting toxicities or new safety signals after up to 17 months follow-up. All 13 patients received A2B694, were efficacy-evaluable, and had A2B694 detected post-infusion in peripheral blood. While A2B694 was not detected in tumor biopsies collected in patients treated at DL1 (0/2), all patients treated at DL2-DL4 with available biopsies (3/3) had detectable A2B694 in the tumor microenvironment. A patient with KRAS G12V /STK11 co-mutated NSCLC who had progressed on carboplatin, pemetrexed, and pembrolizumab achieved a complete response (CR) at D90 post-infusion per RECIST 1.1 by central review and had a confirmed CR at D180. In addition, PET-CT scan and ctDNA on D190 demonstrated no evidence of disease. On D243, the patient had a CNS relapse, with an ongoing non-CNS CR per RANO-BM at D284. At M12, the patient's CT showed no new findings and persistence of A2B694 in the blood was confirmed by ddPCR. Conclusions: We report the first patient with NSCLC to have a CR after CAR T. Overall, A2B694 demonstrated manageable safety and tolerability in patients with advanced solid MSLN-expressing tumors with tumor-associated HLA-A*02 LOH. The maximum tolerated dose has not been reached; dose-escalation continues. Clinical trial information: NCT06051695 .
Impactof MET amplification (amp) on telisotuzumab vedotin (Teliso-V) efficacy and safety in 2L+ non-squamous (NSQ) EGFR wild-type (WT) NSCLC with c-Met protein ov
Mansfield, Aaron Scott, Daaboul, Nathalie , Horinouchi, Hidehito, Baijal, Shobhit , Lu, Shun, Ratajczak, Christine, Öhrling, Katarina, Patel, Shilpen, Woll, Kellie, Mhaske, Pallavi, Zhang, Jianhai, Verma, Mukesh, Zhao, Weilong , Roberts-Rapp, Lisa, Zhang, Nancy, Ansell, Peter, Navas, Tony , Camidge, David Ross , Bar, Jair , Horinouchi, Hidehito , Ratajczak, Christine K. , Sun, Yan , Roberts-Rapp, Lisa A., Navas, Tony A.

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 8524-8524

10.1200/jco.2026.44.16_suppl.8524 Get It

8524 Background: Teliso-V is a c-Met–directed antibody-drug conjugate comprising telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E (MMAE) payload. In the Ph2 LUMINOSITY study (NCT03539536), Teliso-V showed durable responses and manageable safety (Camidge et al, JCO 2024;42:3000-11) resulting in its accelerated approval in locally advanced/metastatic NSQ NSCLC with high c-Met protein OE (3+, ≥50%), as determined by an FDA-approved test. MET amp is a negative prognostic risk factor in advanced NSCLC, frequently associated with recurrent disease. High levels of MET amp and c-Met OE are hallmarks of MET -addicted tumors. Here, we analyzed the effects of MET amp on clinical responses to Teliso-V in LUMINOSITY. Methods: MET amp was evaluated by FISH and ctDNA in baseline samples from 108 NSQ EGFR WT NSCLC pts with c-Met OE (3+, ≥25%). MET amp by FISH was defined as having focal MET amp (MET/CEP7 ≥2.0) with MET gene copy number (GCN) ≥4. MET amp (focal) by ctDNA was defined as having plasma MET GCN ≥4 with no co-amplification in CDK6 and EGFR. c-Met OE by Immunohistochemistry (IHC; SP44) was defined as 3+ tissue staining intensity in ≥25% tumor cells (high c-Met OE: 3+, ≥50%; intermediate [int] c-Met OE: 3+, 25% to 49%). Exploratory analysis of tumor response was assessed in 76 efficacy evaluable pts with c-Met OE and MET amp assay results. Results: MET amp was detected in 34% (37/108) of pts with c-Met OE (3+, ≥25%) and was enriched by c-Met levels: 22% (11/50) in pts with Int c-Met OE (3+, 25% to 49%) and 45% (26/58) in pts with high c-Met OE (3+, ≥50%). The effects of MET amp on tumor response in LUMINOSITY are shown in Table 1. The majority of c-Met OE pts (79%) with PFS ≥10 mo (n=14) had GCN ≥10 and/or c-Met IHC 3+ ≥50%. No new safety signals were reported in pts with c-Met OE and MET amp. Conclusions: MET amp is more common in pts with high c-Met OE in this retrospective subgroup analysis. Tumor activity with Teliso-V was observed regardless of MET amp status. The impact of MET amp in pts with c-Met OE will be further evaluated in ongoing Phase 3 study (NCT04928846). Teliso-V efficacy in NSQ EGFR -WT NSCLC pts with c-Met OE with or without MET amp in LUMINOSITY. Total c-Met OE(3+, ≥25%) Total c-Met OE(3+, ≥25%) Intermediate c-Met OE(3+, ≥25%-49%) Intermediate c-Met OE(3+, ≥25%-49%) High c-Met OE(3+, ≥50%) High c-Met OE(3+, ≥50%) MET amp(N) No (N=53) Yes (N=23) No (N=30) Yes (N=7) No (N=23) Yes (N=16) ORR %(95% CI) 28 (18.0, 41.6) 39 (22.2, 59.2) 23 (11.8, 40.9) 57 (25, 84.2) 35 (18.8, 55.1) 31 (14.2, 55.6) PFS,median, mo(95% CI) 5.26 (3.71, 8.11) 8.02 (4.47, 14.65) 5.32 (2.69, 8.11) 7.52 (4.47, NA) 4.17 (3.25, 8.87) 8.02 (3.06, 25.92) OS,median, mo(95% CI) 14.5 (8.18, 17.38) 13.86 (6.54, 22.24) 14.03 (3.65, 17.02) 9.79 (6.54, NA) 16.26 (5.59, 36.44) 13.86 (3.06, 30.29)
Differences in central versus local lab PD-L1 classification in the ALCHEMIST Alliance A151216 non–small cell lung cancer (NSCLC) study.
Kozono, David E., Giri, Sharmila, Hillman, Shauna L., Nair, Meghana , Sands, Jacob, Gianani, Roberto, Sholl, Lynette M., Yu, Hui, Tan, Angelina D., Watson, Mark, Wen, Yujia , Hirsch, Fred R., Oxnard, Geoff, Malik, Shakun , Stinchcombe, Tom, Mandrekar, Sumithra J. , Kozono, David , Giri, Sharmila, Sands, Jacob , Sholl, Lynette M. , McShane, Lisa M. , Chaft, Jamie E. , Gerber, David E. , Govindan, Ramaswamy , Hirsch, Fred R., Stinchcombe, Thomas E.

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 8057-8057

10.1200/jco.2026.44.16_suppl.8057 Get It

8057 Background: The NCI Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST) study tested resected stage II-IIIB(N2) NSCLC for targetable EGFR and ALK alterations and PD-L1 expression to screen patients for biomarker-driven adjuvant therapy trials (NCT02194738). Local lab results were requested when available for comparison to central lab results. Methods: We identified patients with both central and local PD-L1 results in the ALCHEMIST adjuvant immunotherapy study screening population. Discrepancies in tumor proportion score (TPS) between central and local PD-L1 were defined using prespecified cut-points (granular: <1%, 1-<5%, 5-<10%, 10-<20%, 20-<30%, 30-<40%, 40-<50%, 50-60%, 60-<70%, 70-<80%, 80-<90%, 90-<100%; clinical: <1%, 1-<50%, 50-100%). Large discrepancies were defined as ≥ 50 percentage point differences; for these cases, local PD-L1 and hematoxylin & eosin-stained slides were requested. These and all central slides were digitally scanned at 40X. Three expert pathologists reviewed the scanned slides in a blinded fashion. Differences between patient or tumor characteristics were assessed by Chi-square and Wilcoxon rank sum tests. Percent agreement was computed within and between the reviewers. Results: Central and local PD-L1 results were available for 497 patients. 177 cases (36%) had discrepancies that placed patients in different clinical TPS categories (<1%, 1-<50%, 50-100%). Among these, 43 cases had large TPS discrepancies; 14 had available local testing slides. 46 of the 320 cases without discrepancy were randomly selected as controls. No patient or tumor characteristics were associated with discrepancy, including tumor location, histology, grade or cancer stage (p > 0.05). Pairwise comparisons of TPS according to three pathologists re-reading the same scanned PD-L1 slides showed similar levels of disagreement in clinical TPS category whether there was initial discrepancy between central and local results (24%, 34%, and 23%; mean 27%) or not (33%, 30%, and 20%; mean 28%). Among the 14 cases with large initial discrepancies and local slides available, there was agreement in clinical TPS category when the anonymized central and local scanned slides were re-read by the pathologists in 54%, 38%, and 43% of cases, despite 100% non-agreement in initial reads. There were higher rates of agreement when the tested slides both originated from the same (100%) versus different (35%) blocks, when the same (48%) versus different (40%) PD-L1 antibodies were used, and when the cases were of non-squamous (52%) versus squamous (14%) cell carcinoma. Conclusions: There are substantial differences in PD-L1 TPS read by pathologists that can result in placement of patients in different categories commonly used for clinical management. These differences have clear implications in clinical trials and routine patient care.
Adjuvant erlotinib versus observation after complete resection of EGFR -mutant NSCLC: Final overall survival results of Alliance A081105.
Mandrekar, Sumithra J. , Kozono, David E., Sands, Jacob, Giri, Sharmila, Neal, J, Constantine, Michael, Bazhenova, Lyudmila, Tan, Angelina D., Gandara, David R., Kelly, Karen, Ramalingam, Suresh S., Oxnard, Geoff, Malik, Shakun , Vokes, Everett E., Stinchcombe, Tom, Govindan, Ramaswamy , Kozono, David , Chaft, Jamie E. , Gerber, David E. , Sands, Jacob , Masters, Gregory A. , Neal, Joel W. , Bazhenova, Lyudmila , Bradley, Jeffrey D. , Gandara, David R. , Ramalingam, Suresh S. , Vokes, Everett E. , Stinchcombe, Thomas E.

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 8001-8001

10.1200/jco.2026.44.16_suppl.8001 Get It

8001 Background: The ALCHEMIST clinical trial platform, launched by the National Clinical Trials Network (NCTN) in 2014, screened patients with resected non-small cell lung cancer (NSCLC) for molecular markers and tailored post-operative adjuvant therapy trials. A081105 evaluated whether adjuvant erlotinib improved overall survival (OS) following complete resection in patients with early stage EGFR mutated lung adenocarcinoma. Methods: A081105 was a randomized phase III trial enrolling patients with completely resected stage IB (≥4 cm), II, or IIIA non-squamous NSCLC (per the 7 th TNM staging classification) harboring EGFR exon 19 deletion or L858R mutations. Patients were randomized 1:1 to erlotinib 150 mg daily for up to 2 years or placebo/observation, stratified by stage, prior chemotherapy, EGFR mutation subtype, and ECOG performance status. The primary endpoint was OS in the per-protocol (PP) population with centrally confirmed EGFR mutations, designed to detect a hazard ratio (HR) of 0.67 in favor of erlotinib with a power of 86% and one sided type I error rate of 5%. Secondary endpoints included OS and disease free survival (DFS) in a modified intent-to-treat (mITT) population with local or centrally confirmed EGFR mutations, and safety. A prespecified backstop analysis was conducted after a minimum of 5 years of follow-up on all patients. Results: Trial enrollment was discontinued when 390 of the intended 450 patients had been enrolled due to the proven benefit of adjuvant osimertinib. Among 390 enrolled patients, the arms were balanced for age (median: 67.0 years), sex (70% female), race (70% white), stage (II: 51%, IIIA: 37%), prior chemotherapy (82%), ECOG PS 0 (60%), and exon 19 deletion (57%). Adjuvant erlotinib did not significantly improve OS compared with placebo/observation in the overall PP population (364 patients, 108 events, HR 0.89; 95% CI, 0.59–1.34; 1-sided P = 0.29) or within exon 19 deletion (HR: 0.94) or L858R mutation (HR: 0.82) subgroups. Five-year OS rates were 78.6% versus 77.9%, respectively. Results were consistent in the mITT analysis (379 patients, 113 events, HR 0.86; 95% CI, 0.58–1.28). Erlotinib improved DFS (mITT: 181 events, median: 68 vs 50 months, HR 0.74; 95% CI, 0.55–1.01). Across both arms, 11% of patients started non-protocol treatment (Osimertinib: 9%) prior to disease progression, and 9% withdrew consent for all follow-up prior to recurrence. In the erlotinib arm, 3 deaths on study were reported; grade 3 or higher adverse events were reported on 39% of patients. Median duration of treatment on Erlotinib arm was 16 months; only 37% of patients completed the planned treatment. Conclusions: In resected EGFR -mutant NSCLC, adjuvant erlotinib did not improve overall survival but improved DFS. Additional studies are exploring efficacy in selected subsets of patients using genomics and proteomic analyses. Clinical trial information: NCT02193282 .
Real-world outcomes comparing the use of GLP-1 agonists in patients with multiple myeloma and comorbid obesity: A propensity score–matched analysis from a global federated health research network.
Syal, Arshi , Arya, Yajur , Mahadevia, Himil, Jones, Colton, Palma, Angimar Uriepero, Batra, Nitya, Varadi, Gàbor, Mahadevia, Himil

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7548-7548

10.1200/jco.2026.44.16_suppl.7548 Get It

7548 Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity, and emerging evidence suggests their benefits beyond glycemic control, including cardiovascular effects and potential anti-inflammatory and anti-proliferative properties. Therapeutic advances in multiple myeloma (MM) have improved the overall life-expectancy in our patients. However, metabolic comorbidities remain common, likely driven by disease burden, functional decline, ongoing inflammation, and treatment related effects. Our study evaluates the impact of GLP-1 receptor agonists on outcomes in patients with MM, exploring potential interactions between metabolic modulation and disease outcomes. Methods: We conducted a real-world retrospective cohort study using the TriNetX Global Collaborative Network, covering January 2000 to December 2025, encompassing data from 168 global healthcare organizations. Patients aged 18 and above with multiple myeloma were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and various comorbidities. We assessed outcomes including overall mortality, myocardial infarction (MI), ischemic stroke, sepsis, anemia, pancreatitis, venous thromboembolism (VTE), and ED visits. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: We identified 1716 patients with MM and obesity who received GLP-1 receptor agonists, and 13,491 patients with MM and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 1712 patients with well-balanced baseline characteristics. We followed these patients for 5 years from treatment initiation. Patients with MM who received GLP-1 had a significantly lower risk of overall mortality (Hazard Ratio [HR]: 0.423, 95% CI: 0.351-0.509, p-value <0.001), MI (Risk Difference [RD]: -3.6 %, 95% CI: -5.4 % to -1.7 %, p-value <0.001), ischemic stroke (RD: -1.7 %, 95% CI: -3.3 % to -0.1 %, p-value = 0.04), sepsis with and without shock (RD: -3.0 %, 95% CI: -4.9 % to -1.1 %, p-value = 0.002), and anemia (RD: -9.6 %, 95% CI: -12.9 % to -6.4 %, p-value <0.001). There was no statistically significant difference in the rates of VTE, ED visits, and pancreatitis between the two cohorts. Conclusions: Our study revealed that patients with MM with obesity who received GLP-1 therapy had significantly lower rates of overall mortality, MI, ischemic stroke, sepsis with and without shock, and anemia. Additional longitudinal cohort studies are required to explore the associations between these agents and inform clinical practice guidelines in these patients.