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.
Allison Betof Warner, MD, PhD, reviews important clinical research in the treatment of advanced melanoma, including tumor-infiltrating lymphocyte (TIL) therapy, the role of this innovative treatment in advanced melanoma, and relevant data, peer-reviewed literature, and FDA approvals in 2024. She also provides a look ahead at what is on the horizon in 2025 with regard to care for patients with advanced melanoma.
The ASCO Post Staff
Kent Shih, MD, of Tennessee Oncology, presents three patients cases that show how the use of gene-expression profile testing guides patient and practitioner decision-making when choosing the appropriate path of adjuvant treatment among individuals with melanoma.
The phase III frontMIND trial demonstrated improved outcomes vs R-CHOP in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), paralleling the POLARIX trial. Despite efficacy, tafasitamab/lenalidomide/R-CHOP has not achieved comparable guideline adoption. Uncertainty regarding overall survival benefit, limited follow-up, cross-trial comparisons, and implementation complexity may contribute to the underutilization of this regimen despite its manageable toxicity.
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.
