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ASCO 2025 Spotlight: The Trials Making Headlines 

July 14, 2025
Author: Abby Kim, PharmD, BCOP

The 2025 American Society of Clinical Oncology (ASCO) annual meeting lived up to its reputation as the premier global stage for oncology delivering a wave of data and reinforcing the momentum of precision medicine and immunotherapy across multiple tumor types. Let’s explore key practice-changing trials, their outcomes and their potential impact on the managed care landscape. 

Breast cancer: Targeted therapies redefining strategies 

The DESTINY-Breast09 trial marked a pivotal moment in the treatment of HER2-positive metastatic breast cancer, offering the first major advancement in the first-line setting in over a decade. This phase 3 study evaluated the use of trastuzumab deruxtecan (T-DXd) – an antibody drug conjugate - plus pertuzumab against the current longstanding chemotherapy-based regimen of docetaxel, trastuzumab and pertuzumab (THP). The results were striking as the T-DXd combination reduced the risk of progression by 44% (HR 0.56, p < 0.00001) with a median progression free survival (mPFS) of 40.7 months vs 26.9 months compared to THP.  Overall survival data remains immature but the objective response rate (ORR) of 85.1% and median duration of response exceeding 3 years positions this as a potential new standard of care (SOC).¹

Impact to patients, providers and payers: Adoption of this regimen in managed care will currently require case-by-base evaluation, as it is not yet published in full or included in the National Comprehensive Cancer Network (NCCN) guidelines.2 In addition, it must be noted that for patients with hormone receptor positive (HR+) disease, endocrine therapy can be added on and should be considered in coverage decisions.¹⁻²

The SERENA-6 trial highlighted the power of circulating tumor DNA (ctDNA) to outpace imaging by using molecular clues to guide treatment changes before clinical progression in HR+, HER2-negative advanced breast cancer. Among 3,526 patients screened, 315 with newly detected ESR1 mutations, a key driver of aromatase inhibitor (AI) resistance, were randomized to camizestrant, a next-generation SERD under investigation, or continued AI plus a CDK4/6 inhibitor. Patients switched to camizestrant at signs of molecular progression had a mPFS of 16 months vs. 9.2 months in the AI group with a significantly better quality of life and favorable safety profile.³

Impact to patients, providers and payers: SERENA-6 introduces a new model of molecularly guided treatment application that has the potential to delay disease progression and reduce downstream costs. While routine ctDNA testing is not yet SOC or widely covered, payers must begin preparing for its integration as molecular monitoring becomes central to personalized cancer treatment. If approved, camizestrant integration into practice will depend on guideline inclusion and the readiness of the community to support biomarker-driver treatment switches before radiographic progression.⁴ 

Gastrointestinal cancers: Immunotherapy reshaping the landscape 

The ATOMIC trial is the first phase 3 study to show that adding atezolizumab to standard adjuvant chemotherapy significantly improves outcomes in patients with stage III dMMR colon cancer – a molecular subtype that is notably more common in early-onset colorectal cancer which is on the rise. In this randomized trial of 712 patients, those who received mFOLFOX6 (5-FU, leucovorin, oxaliplatin) plus atezolizumab followed by atezolizumab monotherapy achieved a 3-year disease free survival (DFS) of 86.4% vs. 76.6% with chemotherapy alone resulting in a 50% reduction in the risk of recurrence or death (HR 0.50, p < 0.0001). The benefit was consistent across age groups and risk categories positioning this as a potential new SOC.⁵

Impact to patients, providers and payers: The data signals a shift toward adjuvant immunotherapy in early-stage colon cancer with NCCN adding this as a 2A recommendation in their most recent update. Payers should prepare for increased use of molecular testing to identify dMMR status and for the cost implications of adding immunotherapy to adjuvant treatment.⁵⁻⁶ 

Building on the momentum of adjuvant immunotherapy seen in the ATOMIC trials, the MATTERHORN trial demonstrated adding durvalumab to perioperative FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) chemotherapy significantly improves outcomes in patients with resectable, locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. In this phase 3 study of 948 patients, the addition of durvalumab led to a statistically significant improvement in event-free survival (EFS) translating to a 29% reduction in the risk of progression, recurrence or death. This represents a potential shift in perioperative SOC for a disease with persistently high recurrence rates.⁷

Impact to patients, providers and payers? The MATTERHORN trial underscores the growing role of immunotherapy in curative-intent treatment, expanding its reach beyond the metastatic setting. This evolution presents both opportunity and complexity. While improved EFS may reduce long-term costs associated with recurrence, payers should prepare for the upfront investment of immunotherapy in gastric cancers.  

GLP-1 receptor antagonists and obesity related cancers 

We’d be remiss not to spotlight the GLP-1 data that added a new dimension to this year’s meeting – especially in light of Prime Therapeutics (Prime) continued research and leadership in this space. In a large real-world analysis of 85,000 adults with obesity and type 2 diabetes, researchers evaluated whether the use of a GLP-1 reduced the risk of obesity-related cancers compared to DPP-4 inhibitors, which are weight neutral. Over a median follow-up of 3.9 years, GLP-1 use was associated with a 7% lower risk of obesity-related cancers (adjusted HR 0.93, p = 0.005) and an 8% reduction in all-cause mortality (adjusted HR 0.92, p = 0.001). The protective effect was particularly notable for colorectal cancers which are on the rise in both young and older populations. In addition, the benefit was more pronounced in women. These findings suggest that GLP-1s may offer dual benefits in both metabolic disease management and cancer prevention.⁸

Impact to patients, providers and payers? While these agents are already under scrutiny for their high cost, this new data may support broader coverage over time in high-risk populations. Payers may need to consider long-term value-based frameworks that account for downstream savings from reduced cancer incidence.⁹

These highlights represent just a glimpse of the groundbreaking data presented at the 2025 ASCO Annual Meeting. With many more studies presented and poised to reshape clinical practice we can look forward to continued innovation and insights at next year's gathering. 

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References 
  1. Tolaney SM, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line treatment of patients with HER2-positive advanced/metastatic breast cancer: Interim results from DESTINY-Breast09. J Clin Oncol. 2024;42(16). 
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Breast Cancer. Version 4.2025. Published June 2025. Accessed July 7, 2025. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. 
  3. Turner NC, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor for treatment of emergent ESR1 mutations during first-line endocrine-based therapy in HR+/HER2– advanced breast cancer: Phase 3 SERENA-6 trial. J Clin Oncol. 2024;42(16). 
  4. Tie J, Gibbs P, Lipson D, et al. Circulating tumor DNA analysis in cancer: Recommendations for clinical implementation. Nature. 2023;622(7985):123–131. 
  5. Sinicrope FA, Ou FS, Arnold D, et al. Randomized trial of chemotherapy with or without atezolizumab as adjuvant therapy for stage III dMMR colon cancer (ATOMIC trial). J Clin Oncol. 2024;42(16). 
  6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Colon Cancer. Version 4.2025. Published June 2025. Accessed July 7, 2025. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428. 
  7. Janjigian Y, Al-Batran SE, Wainberg Z, et al. Event-free survival in MATTERHORN: A phase 3 study of durvalumab + FLOT in resectable gastric/gastroesophageal junction cancer. J Clin Oncol. 2024;42(16). 
  8. Mavromatis L, Surapaneni A, Mehta S, et al. Glucagon-like peptide-1 receptor agonists and incidence of obesity-related cancer in adults with diabetes: A target-trial emulation study. J Clin Oncol. 2024;32(16). 
  9. Kraus A. Industry Voices—The GLP-1 status quo is no longer acceptable. It is changeable. Fierce Healthcare. Published May 28, 2024. Accessed July 7, 2025. https://www.fiercehealthcare.com/payers/industry-voices-glp-1-status-quo-no-longer-acceptable-it-changeable. 

 
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