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PURPOSE:To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations. METHODS:This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS:This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date. RECOMMENDATIONS:Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Didactic lectures play an important role in hematology/oncology fellowship education. How each program structures their curricula is determined independently. To improve the trainee experience, identifying best practices is essential, but limited data about program structure exist. This marks the first cross-sectional analysis of hematology/oncology fellowship didactic curricula from a heterogenous group of programs to-date. Twenty-eight US Accreditation Council for Graduate Medical Education-accredited hematology/oncology fellowship programs were included. Local principal investigators completed a 21-question survey containing a series of multiple-choice and open-ended questions to understand participating programs’ educational curricula and structure. Responses were analyzed using descriptive statistics for multiple-choice questions and thematic analysis for open-ended questions. All participating programs completed the background assessment (100
TPS4204 Background: Patients with GC/GEJC often present with advanced disease, and prognosis for these patients is poor, with a 5-year relative survival rate of ~5%, highlighting a need for new treatment options. HER2 overexpression/amplification occurs in ~20% of cases. Adding immune checkpoint inhibition to trastuzumab (anti-HER2 monoclonal antibody) and chemotherapy has shown clinical benefit in patients with advanced HER2-positive GC/GEJC (Janjigian YY, et al. N Engl J Med 2024), and led to the approval of pembrolizumab (programmed cell death-1 [PD-1] inhibitor), trastuzumab, and chemotherapy for HER2-positive GC/GEJC with programmed cell death ligand-1 combined positive score (PD-L1 CPS) ≥1. T-DXd (a HER2-directed antibody-drug conjugate) is approved for the treatment of patients with locally advanced/metastatic HER2-positive GC/GEJC who have received a prior trastuzumab-based regimen. In addition, dual inhibition of PD-1 or PD-L1 and the immune checkpoint T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has shown encouraging results across multiple tumor types, without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is a monovalent, bispecific, humanized IgG1 monoclonal antibody targeting both PD-1 and TIGIT receptors that has shown encouraging efficacy with manageable safety as monotherapy in non-small-cell lung cancer (Hiltermann TJN, et al. WCLC 2024. Oral presentation 1751) and with chemotherapy in HER2-negative GC/GEJC (Herrero FR, et al. Ann Oncol 2024. Abs 1422P). Methods: ARTEMIDE-Gastric01 (NCT06764875) is a phase 3, randomized, open-label, sponsor-blinded, multicenter, global study that will assess the efficacy and safety of rilvegostomig with T-DXd and chemotherapy as 1L treatment in HER2-positive GC/GEJC with PD-L1 CPS ≥1. Approximately 840 participants (pts) will be randomized to Arm A: rilvegostomig + T-DXd + investigator’s (INV) choice of capecitabine or 5-fluorouracil (5-FU); Arm B: pembrolizumab + trastuzumab + INV choice of 5-FU and cisplatin (FP) or capecitabine and oxaliplatin (CAPOX); Arm C: rilvegostomig + trastuzumab + INV choice of FP or CAPOX. Eligible pts will have previously untreated, unresectable, histologically confirmed, locally advanced/metastatic HER2-positive and PD-L1 CPS ≥1 GC/GEJC and an ECOG performance status of 0 or 1. Dual-primary endpoints are progression-free survival (RECIST v1.1; blinded independent central review) and overall survival in all randomized pts. Secondary endpoints include safety/tolerability, objective response rate, and duration of response. Enrollment is planned across ~25 countries in Asia, Australia, Europe, and North and South America. Clinical trial information: NCT06764875 .
Two years of adjuvant abemaciclib plus endocrine therapy is approved and guideline-recommended in patients (pts) with HR+, HER2-, node-positive, early breast cancer (EBC) at high risk of recurrence. In initial real-world studies, the high rate (>85%) of treatment (tx) persistence beyond 3 months suggests that adjuvant abemaciclib is well-tolerated in routine clinical practice.1,2 Dose reductions were associated with higher persistence in prior studies and clinical trial data have shown that efficacy of abemaciclib was maintained with dose reductions. This study describes 6-month tx persistence and dosing patterns in pts with HR+, HER2-, node-positive EBC initiating abemaciclib 150 mg twice daily (BID). Retrospective data were accessed from the US de-identified Flatiron Health Research Database. Adults with HR+, HER2-, node-positive, EBC, who initiated abemaciclib 150 mg BID from Jan 2022-Jun 2024 were eligible and further characterized by ≥1 vs no dose reduction. Data cut-off was Dec 2024. Persistence rate was the proportion of pts on abemaciclib >6 months, allowing for ≤60-day medication gap within this period. Time to dose modifications and reasons for discontinuation (DC) were summarized. Subgroup analyses were conducted in pts confirmed as meeting the monarchE high-risk criteria (N2, N3, or N1 plus Grade 3 and/or tumor >5 cm). All analyses were descriptive. Of 1063 eligible pts, median age was 56 years (IQR 47, 65). Most had N1 (48%) or N2 (34%) disease. Median follow-up was 17.5 months (IQR 11, 25). Tx persistence at 6 months was 75%. DC was mostly due to adverse events (AEs; 19%) and <1% due to recurrence. Approximately 50% of pts had ≥1 dose reduction. Persistence was 85% in pts with ≥1 dose reduction and 64% in pts with no dose reductions. 70% of pts who DC’d by 6 months did not have a dose reduction. Median time from start of abemaciclib to first dose change and/or hold was 49 days (IQR 23, 111). During the first 30 days of tx and Days 31-90, DCs due to AEs were lower in pts with dose reductions vs pts with no dose reductions (Table). Persistence and use of dose reductions were similar in pts confirmed as meeting the monarchE high-risk criteria. In US clinical practice, a majority (75%) who initiated adjuvant abemaciclib continued abemaciclib beyond 6 months. Tx persistence was higher among pts with dose reductions relative to those with no dose reductions, and rates of early DCs due to AEs were low in pts with dose reductions. Given that dose reductions in monarchE were not associated with reduced efficacy, these additional real-world data support the use of early dose modifications to improve tolerability and tx persistence for adjuvant abemaciclib in pts with high risk of recurrence. H. Soliman, S. Dent, A. Liepa, V. Stefaniak, M. Huang, T. Sugihara, K. Moreira, K. Hudson, M. Goetz. Treatment Persistence and Dose Modifications in US Patients with HR+, HER2-, Node-Positive, Early Breast Cancer Treated with Adjuvant Abemaciclib [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-09.
The combination of CDK4/6 inhibitor (CDK4/6i) (abemaciclib [abema], palbociclib [palbo], or ribociclib [ribo]) and endocrine therapy (ET) is standard-of-care for patients (pts) with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC). These agents demonstrate similar improvements in progression-free-survival, but only ribo has shown consistent overall survival (OS) benefit across multiple phase III trials. This clinical benefit, as well as toxicity profiles, comorbid conditions, physician familiarity, and pt-specific factors, may influence initial selection and switching patterns in clinical practice. This study characterizes switching patterns in pts initiating first-line (1L) CDK4/6i + ET. We conducted a retrospective cohort study using the IntegraConnect PrecisionQ de-identified electronic health record (EHR) database, which includes data on >3 million cancer pts treated across >500 US care sites. Pts with HR+/HER2− mBC who initiated 1L treatment with abema, palbo, or ribo between 02/26/2018 and 05/16/2025 were included. Switching was defined as discontinuation of the initial CDK4/6i followed by initiation of another CDK4/6i. Data on whether the accompanying ET was changed at the time of the CDK4/6i switch were not assessed. Pts (n=179) were selected for a subset analysis based on the availability of curated discontinuation reasons (toxicity, disease progression, personal/financial), which were manually abstracted from clinical documentation. Pts were stratified by initial CDK4/6i, documented reason for switching, and time to switch (≤30, 31-90, 91-180, >180 days). Differences in time to switch by reason were assessed using Wilcoxon rank-sum testing. Among 11,928 pts with HR+/HER2− mBC who initiated 1L treatment with CDK4/6i + ET, 7,499 used palbo, 2,371 used ribo, and 2,058 used abema. Of these pts, 577 pts (7.7%) switched from palbo, 307 (12.9%) from ribo, and 264 (12.8%) from abema to an alternative CDK4/6i. Toxicity was the most frequently documented reason for switching, reported in 91.8% of pts who switched from abema, 69.7% from ribo, and 49.5% from palbo. The median duration of therapy prior to switching for toxicity was longest for palbo (131 days), followed by abema (96 days) and ribo (95 days). Disease progression as a reason for switching was most commonly reported in pts initially treated with palbo (42.3%), followed by ribo (21.2%) and abema (6.1%). Pts who switched due to disease progression had a significantly longer time to switch than those who switched for other reasons (median 444 vs. 141 days; Wilcoxon P<0.0001). Switches occurred most commonly after >180 days for palbo (58.8%), whereas earlier switches (≤180 days) were more frequent for abema and ribo (∼70%). Among those who switched from palbo, 64.1% switched to abema and 35.9% to ribo. Among pts who switched from ribo, 61.2% switched to palbo and 38.8% to abema. Of those switching from abema, 75.4% switched to palbo and 24.6% to ribo. In this real-world analysis of 1L CDK4/6i use in HR+/HER2- mBC, intra-class switching was common and most often driven by toxicity rather than disease progression. Time to switch varied by initial agent and reason for discontinuation with palbo users more frequently switching later and for progression, while earlier switches from abema and ribo were largely due to intolerance. This study’s retrospective design may introduce selection bias, and reasons for switching were not always documented. Comorbidities, tumor burden, prior treatments, and access to care were not captured, representing potential unmeasured confounders. Additionally, evolving data availability and drug approvals during the study period may have influenced treatment choices and switching patterns. S. Reganti, R. Choksi, V. Gorantla, F. Kudrik, D. Patt, S. Reddy, S. Rosenfeld, D. Parris, M. Wang, A. Rui, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, R. Mahtani. Real-world rate of switching and reasons for switching among CDK4/6i drugs among first-line metastatic HR+/HER2- breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-12-13.
