Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, reviews currently available therapies for patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC), noting the importance of genomic testing to identify individuals eligible for treatment with these agents. He discusses the two FDA-approved second-line drugs in this space—sotorasib and adagrasib—touching on their efficacy and associated adverse events. He also mentions divarasib, an investigational next-generation KRAS G12C inhibitor, which showed superiority over both sotorasib and adagrasib in a recent head-to-head phase III trial.
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.
Jennifer Gile, MD, of Willamette Valley Cancer Institute, reviews findings from the POLARIX study, a double-blind, placebo-controlled, international phase III trial that evaluated pola-R-CHP—a modified regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), in which vincristine was replaced with polatuzumab vedotin—as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL). With a 5-year update from the trial being published recently, Dr. Gile discusses long-term results, the regimen’s performance in key high-risk subgroups, and how the study altered the front-line management of this disease.
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.
The ASCO Post Staff
Raajit K. Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses management strategies for these two conditions often associated with myelofibrosis. He discusses the role of Janus kinase inhibitors; using older therapies in novel ways; how stem cell transplantation is considered; and more.
References
- Marrone M, Morere L, Oladapo A, et al: Hematologic improvement experienced by pacritinib-treated patients with myelofibrosis in real-world clinical settings. Blood 144 (suppl 1):3814, 2024.
- Rampal RK, Verstovsek S, Devlin SM, et al: Safety and efficacy of combined ruxolitinib and thalidomide in patients with myelofibrosis: A phase II study. Blood 134 (suppl 1):4163, 2019.
