ESR1 mutations are a major mechanism of acquired endocrine resistance in hormone receptor–positive metastatic breast cancer and are associated with poorer outcomes. Serial ctDNA testing enables dynamic detection of emergent ESR1 mutations and clonal evolution, potentially informing treatment selection. As Neil M. Iyengar, MD, outlines via a patient case and deeper data review, ESR1 testing strategies should be individualized based on treatment duration, disease stability, and patient preferences.
The ASCO Post Staff
Arvind N. Dasari, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses data presented at the ESMO Gastrointestinal Cancers Congress 2025, which showed that adding circulating tumor DNA (ctDNA) testing to current standard of care surveillance for patients with colorectal cancer (CRC) better identified patients who are appropriate candidates for metastasis-directed therapy.
Reference
- Dasari NA, Nakamura Y, Sorscher S, et al: Clinical utility of including circulating tumor DNA monitoring in standard of care colorectal cancer surveillance. ESMO Gastrointestinal Cancers Congress 2025. Abstract 2O.
Access to second-line chimeric antigen receptor (CAR) T-cell therapy remains suboptimal in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Matthew Lunning, DO, FACP, of the University of Nebraska Medical Center, explains that prior tafasitamab exposure may theoretically affect CD19 detection or antigen persistence, but clinical evidence demonstrating impaired subsequent CAR T-cell efficacy is lacking. Real-world data have not established CD19 loss, supporting continued consideration of CAR T-cell therapy following tafasitamab-based treatment.
The ASCO Post Staff
Erika Hamilton, MD, Director, Breast Cancer Research at Sarah Cannon Research Institute, provides a look at “where we stand in 2025” in the field of oral selective estrogen receptor degraders (SERDs) for patients with estrogen receptor–positive, HER2-negative breast cancer. She discusses the first and only FDA-approved oral SERD, elacestrant, indicated for use after CDK4/6 inhibitor therapy in patients with ESR1 mutations; reviews agents still being tested in clinical trials, such as imlunestrant and camizestrant; and highlights the role of oral SERDs as both monotherapies and in novel combinations. As Dr. Hamilton explains, “there haven’t been novel endocrine backbones [for these patients] since fulvestrant.”
The ASCO Post Staff
Nikhil Khushalani, MD, Vice Chair for the Department of Cutaneous Oncology at Moffitt Cancer Center, offers his thoughts on the role of immunotherapy in the treatment of advanced cutaneous squamous cell carcinoma (CSCC). Dr. Khushalani discusses the three currently approved immunotherapeutic agents for this disease—cemiplimab-rwlc, pembrolizumab, and cosibelimab-ipdl—and their confirmatory trials as well as adverse event profiles. He also talks about choosing optimal treatment strategies for patients, and studies currently exploring monotherapy vs combination therapy regimens.
References
1. Migden MR, Rischin D, Schmults CD, et al: PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Eng J Med 379:341-351, 2018.
2. Hughes BGM, Guminski A, Bowyer S, et al: A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6. J Am Acad Dermatol 1:68-77, 2025.
3. Grob JJ, Gonzalez R, Bassett-Seguin N, et al: Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase II trial (KEYNOTE-629). J Clin Oncol 25:2916-2925, 2020.
4. Maubec E, Boubaya M, Petrow P, et al: Phase II study of pembrolizumab as first-line, single-drug therapy for patients with unresectable cutaneous squamous cell carcinomas. J Clin Oncol 26:3051-3061, 2020.
5. Clingan P, Ladwa R, Brungs D, et al: Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J Immunother Cancer 10:e007637, 2023.
6. Zandberg DP, Allred JB, Rosenberg AJ, et al: Phase II (Alliance A091802) randomized trial of avelumab plus cetuximab versus avelumab alone in advanced cutaneous squamous cell carcinoma. J Clin Oncol 43:2398-2408, 2025.
