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.
In this second installment of a two-part discussion about ovarian cancer advances for The ASCO Post Newsreels, Ursula A. Matulonis, MD, and Joyce F. Liu, MD, MPH, discuss low-grade serous ovarian carcinoma and an important recently published study. View part 1 of the program to hear them discuss antibody-drug conjugates and clinical trials including PRIMA and ATHENA.
Filmed November 22, 2024
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.
In hormone receptor–positive, HER2-negative metastatic breast cancer, co-occurring ESR1 and PIK3CA mutations create therapeutic complexity. Oral SERDs, including elacestrant, retain activity despite PIK3CA co-mutation and may offer an efficacy–toxicity balance compared with PI3K/AKT pathway inhibitors. Treatment selection should incorporate molecular profile, anticipated efficacy, toxicity, and shared decision-making, states Neil M. Iyengar, MD.
Jennifer Gile, MD, of Willamette Valley Cancer Institute, talks about the first positive phase III trials in the high-risk diffuse large B-cell lymphoma (DLBCL) space—POLARIX and frontMIND. POLARIX established the superiority of a modified regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) called pola-R-CHP, in which vincristine was replaced with polatuzumab vedotin, over standard R-CHOP; frontMIND showed that the addition of the CD19 monoclonal antibody tafasitamab plus the immunomodulatory drug lenalidomide to R-CHOP also improved outcomes over standard R-CHOP. Dr. Gile discusses current considerations when choosing between these regimens and how future research may lead to even more refined patient selection.
