Nikhil Khushalani, MD, on Immunotherapy in Advanced Unresectable CSCC
Thematic Newsreels
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
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.
The ASCO Post Staff
Circulating tumor DNA has many roles in cancer treatment: early diagnosis, tumor profiling, determining response to therapy, and tracking clinical dynamics. In this video, Arvind N. Dasari, MD, MS, of The University of Texas MD Anderson Cancer Center, focuses on it as a marker for measurable residual disease (MRD), which can help to determine risk of disease recurrence in patients with cancer. Dr. Dasari reviews the development of assays for MRD, both tumor-informed and tumor-agnostic, and provides top-level data from several clinical trials on the topic that have informed the role of MRD testing in both the colorectal cancer and general solid tumor space.
References
- Tie J, Wang Y, Lo SN, et al: Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: Overall survival and updated 5-year results from the randomized DYNAMIC trial. 2024 ASCO Annual Meeting. Abstract 108.
- Lieu CH, Yu G, Kopetz S, et al: NRG-GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). 2024 ASCO Gastrointestinal Cancers Symposium. Abstract TPS243.
- Tie J, Wang Y, Loree J, et al: ctDNA-guided adjuvant chemotherapy escalation in stage III colon cancer: Primary analysis of the ctDNA-positive cohort from the randomized AGITG dynamic-III trial (intergroup study of AGITG and CCTG). 2025 ASCO Annual Meeting. Abstract 3505.
- Lumish MA, Jayakumaran G, Fox M, et al: Frequency of minimal residual disease as measured by ctDNA in mismatch repair deficient tumors following curative resection. 2021 ASCO Annual Meeting. Abstract e14520.
- Kotani D, Oki E, Nakamura Y, et al: Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nature Medicine 29:127-134, 2023.
- Kasi PM, Aushev VN, Ensor J, et al: Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study. 2024 ASCO Gastrointestinal Cancers Symposium. Abstract 9.
- Maddalena G, Pellatt AJ, Eluri M, et al: INTERCEPT Program of circulating tumor DNA (ctDNA) testing for minimal residual disease (MRD) in colorectal cancer (CRC): Results from a prospective clinical cohort. 2024 ASCO Gastrointestinal Cancers Symposium. Abstract 27.
- Meyerhardt JA, Shi Q, Fuchs CS, et al: Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer. JAMA 13:1277-1286, 2021.
- Nowak JA, Shi Q, Twombly T, et al: Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702. 2025 ASCO Gastrointestinal Cancers Symposium. Abstract LBA14.
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.
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).
