Benjamin P. Levy, MD, on KRAS G12C–Mutated NSCLC: Current Treatment Landscape
Thematic Newsreels
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.
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
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 ASCO Post Staff
Kent Shih, MD, of Tennessee Oncology, shares three patient cases that illustrate how gene-expression profiling (GEP) in patients with melanoma helps shape the decision to proceed to sentinel lymph node biopsy (SLNB) and how often and thorough follow-up should be with medical oncology.
The ASCO Post Staff
Erika Hamilton, MD, Director, Breast Cancer Research at Sarah Cannon Research Institute, provides a look at “where we stand in 2025” in the field of oral selective estrogen receptor degraders (SERDs) for patients with estrogen receptor–positive, HER2-negative breast cancer. She discusses the first and only FDA-approved oral SERD, elacestrant, indicated for use after CDK4/6 inhibitor therapy in patients with ESR1 mutations; reviews agents still being tested in clinical trials, such as imlunestrant and camizestrant; and highlights the role of oral SERDs as both monotherapies and in novel combinations. As Dr. Hamilton explains, “there haven’t been novel endocrine backbones [for these patients] since fulvestrant.”
The ASCO Post Staff
Nikhil Khushalani, MD, Vice Chair for the Department of Cutaneous Oncology at Moffitt Cancer Center, reviews advances in the adjuvant and neoadjuvant treatment of cutaneous squamous cell carcinoma (CSCC). He discusses the possibility of de-escalating therapy for patients who respond positively to presurgical agents; how to best select postoperative regimens; and ongoing trials in both spaces.
References
- Gross ND, Miller DM, Khushalani NI, et al: Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Eng J Med 387:1557-1568, 2022.
- Gross ND, Miller DM, Khushalani NI, et al: Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: Follow-up and survival outcomes of a single-arm, multicentre, phase 2 study. Lancet Oncol 11:1196-1205, 2023.
- Breukers SE, Traets JJH, van Dijk SW, et al: Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: A randomized phase 2 trial. Nature Medicine. October 8, 2025 (early release online).
- Ladwa R, Lee JH, McGrath M, et al: Response-adapted surgical and radiotherapy de-escalation in resectable cutaneous squamous cell cancer using pembrolizumab: The De-Squamate study. J Clin Oncol 26:2888-2986, 2025.
- Porceddu SV, Bressel M, Poulsen MG, et al: Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: The randomized phase III TROG 05.01 trial. J Clin Oncol 13:1275-1283, 2018.
- Rischin D, Porceddu S, Day F, et al: Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Eng J Med 393:774-785, 2025.
- Koyfman SA, Lee JHJ, Mortier L, et al: Phase 3 randomized trial (KEYNOTE-630) of adjuvant pembrolizumab versus placebo for high-risk locally advanced cutaneous squamous cell carcinoma following surgery and radiation. 2025 ASCO Annual Meeting. Abstract 6000. Presented May 31, 2025.
