Benjamin P. Levy, MD, on Emerging Options for KRAS G12C–Mutated NSCLC: First-Line and Combination Therapies
Thematic Newsreels
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
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.
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.
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.
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
Raajit K. Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, reviews the four FDA-approved Janus kinase (JAK) inhibitors for patients with myelofibrosis, touching upon differences in their mechanisms of action and toxicity profiles. He also discusses clinical trials of add-on drugs to the currently approved JAK inhibitors, which may increase their efficacy and durability, as well as trials of novel JAK inhibitors and immunotherapies targeting CALR.
