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.
The ASCO Post Staff
Atish D. Choudhury, MD, PhD, a medical oncologist and clinical/translational investigator at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, discusses current guideline recommendations for the use of relugolix and leuprolide, relugolix as a combination backbone, and important considerations when applying these data to clinical practice.
References
1. De La Cerda J, Dunshee C, Gervasi L, et al: A phase I clinical trial evaluating the safety and dosing of relugolix with novel hormonal therapy for the treatment of advanced prostate cancer. Target Oncol 3:383-390, 2023.
2. George DJ, Saad F, Cookson MS, et al: Impact of concomitant prostate cancer medications on efficacy and safety of relugolix versus leuprolide in men with advanced prostate cancer. Clin Genitourin Cancer 3:383-392, 2023.
3. Brown G, Belkoff L, Hafron JM, et al: Coadministration of apalutamide and relugolix in patients with localized prostate cancer at high risk for metastases. Target Oncol 1:95-103, 2023.
Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, discusses research into moving KRAS G12C inhibitors from the second to the first line, as well as combining them with immunotherapies and EGFR antibodies. Some potential combinations under investigation include KRAS G12C inhibitors (such as olomorasib, fulzerasib, divarasib, and adagrasib) and single-agent immunotherapy (pembrolizumab) or EGFR-targeting therapies (cetuximab).
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.
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.
