C-POST
2025-07-11
C-POST: Adjuvant Cemiplimab in High-Risk Resected CSCC
A positive phase 3 trial changed the evidence base—but the room quickly moved to the harder questions: who should actually receive adjuvant therapy, what role radiation still plays, and whether immunotherapy belongs before surgery rather than after it.
Meeting 38 unique people after reconnects and duplicate-name reconciliation
Median attendance 90 min among unique attendees
Stayed ≥60 min 74% sustained participation across a long-form discussion
Regeneron 9 attendees identified by Regeneron email domain
What C-POST established
C-POST randomized 415 patients with high-risk resected CSCC after surgery and postoperative radiotherapy to cemiplimab or placebo. At the primary analysis, disease recurrence or death occurred in 24 patients receiving cemiplimab and 65 receiving placebo, corresponding to a hazard ratio of 0.32. Estimated 24-month disease-free survival was 87.1% versus 64.1%.
The question beneath the paper: Does a large reduction in recurrence risk mean adjuvant anti–PD-1 should become routine—or does it make patient selection, sequencing, and treatment burden even more important?
What is proven?
Adjuvant cemiplimab reduces recurrence after complete local therapy in a carefully selected, very-high-risk population.
What is not proven?
C-POST does not establish that cemiplimab can replace postoperative radiation, because both randomized groups received radiation before study therapy.
What changed the discussion?
The competing clinical reality was already neoadjuvant immunotherapy—an approach many participants were using before adjuvant phase 3 data arrived.
Regeneron joined the room—not just the agenda.
The session deliberately brought academic clinicians together with colleagues from Regeneron involved in medical affairs and clinical development. The later JoCO Perspective acknowledged Christopher Zajac, Alyson Baryiames, Sarah Nia, Brian Burleson, Kim Premo, Frank Seebach, Julie Montiel, and Matthew Fury for participating and sharing insights about the development and interpretation of C-POST.
The recap preserves the distinction between participation and independent interpretation: industry colleagues contributed context, while the discussion remained an evidence-focused SoCO Journal Club.
What the survey said
The survey is particularly useful in retrospect because it captured a field already moving faster than the formal evidence base. The visual language below deliberately uses equal-length rails: the percentage is the quantitative signal, while the rail provides alignment rather than a second encoding of magnitude.
The discussion moved beyond the headline result
Participants repeatedly returned to the patient who arrives after surgery but before postoperative RT. The trial proves benefit after radiation; it does not tell clinicians whether systemic therapy can safely replace radiation.
For a resectable parotid metastasis, the majority of surveyed clinicians favored beginning with immunotherapy. That prompted a discussion about whether contemporary practice was already eroding equipoise for surgery-first randomized strategies.
The group considered differences in eligibility, radiation, timing to randomization, dosing schedules, study conduct, and chance. Reconstructed survival curves were used to ask whether the placebo groups actually looked as different as post hoc explanations implied.
When cross-trial speculation became tempting, Matthew Fury emphasized how much information remained unavailable and cautioned against pushing the comparison beyond what the data could support.
A multidisciplinary meeting
The reconciled attendance roster contains 38 unique people, including 9 Regeneron participants. The meeting mixed dermatology, Mohs surgery, surgical oncology, medical oncology, radiation-oriented perspectives, trainees, researchers, and clinical-development colleagues.
Attendance roster View names and affiliations
This roster records meeting attendance and institutional affiliation only.
| Name | Affiliation |
|---|---|
| Adewole S. Adamson | The University of Texas at Austin |
| Adewunmi O. Adelaja | Beth Israel Lahey |
| Alyson Baryiames | Regeneron |
| Andrew D. Knight | Mass General Brigham |
| Brian Burleson | Regeneron |
| Christopher Zajac | Regeneron |
| David Kremer | Regeneron |
| David M. Miller | Mass General Brigham |
| Frank Seebach | Regeneron |
| Gabriella Chefitz | National Institutes of Health (NIAMS) |
| Howard L. Kaufman | Mass Eye and Ear |
| Isaac Brownell | National Institutes of Health |
| Jennifer DeSimone | Inova |
| Juliane Andrade Czapla | Mass General Brigham |
| Julie Montiel | Regeneron |
| Kamaneh Montazeri | Mass General Brigham |
| Karam Khaddour | Dana-Farber Cancer Institute |
| Kevin S. Emerick | Mass Eye and Ear |
| Khalid Garman | National Institutes of Health |
| Kim Premo | Regeneron |
| Krista M. Rubin | Mass General Brigham |
| Larisa Geskin | Columbia University |
| Laura Ferris | University of North Carolina |
| Lauren O’Loughlin | Beth Israel Deaconess Medical Center |
| Madeliene Stump | Mass General Brigham |
| Mariam | — |
| Matthew Fury | Regeneron |
| Molly Yancovitz | Beth Israel Deaconess Medical Center |
| Nikhil Khushalani | Moffitt Cancer Center |
| Paul Nghiem | University of Washington |
| Reed E. Drews | Beth Israel Deaconess Medical Center |
| Ross D. Merkin | Mass General Brigham |
| Sameer Gupta | Mass Eye and Ear |
| Sarah Nia | Regeneron |
| Suzanne Topalian | Johns Hopkins Medicine |
| Vatche Tchekmedyian | MaineHealth |
| Vern Sondak | Moffitt Cancer Center |
| Vishal Patel | George Washington University |
Discussion standouts
Vern Sondak
Pressed on the clinical reality of parotid metastases, the opportunity cost of missing neoadjuvant therapy, and the distinction between saving radiation for salvage versus assuming it is unnecessary.
Nikhil Khushalani
Focused the group on trial equipoise, treatment duration, cost stewardship, and differences in timing between C-POST and KEYNOTE-630.
Isaac Brownell
Raised the provocative question of whether dosing frequency itself might matter in a microscopic-residual-disease setting.
Ross Merkin
Framed the central implementation dilemma: does radiation have a biological role in the positive C-POST strategy, or is it simply a treatment we may eventually learn to omit?
Kevin Emerick
Made the stewardship argument concrete—cost and overtreatment matter when a substantial fraction of patients may never recur.
Matthew Fury
Added sponsor-side trial-development context while repeatedly marking the boundary between reasonable hypotheses and conclusions the available cross-trial data could not support.
The Journal Club became a published Perspective.
The July discussion did not end with the meeting. Its survey data, multidisciplinary debate, and exploratory reconstruction of the C-POST and KEYNOTE-630 survival curves were developed into a Journal of Cutaneous Oncology Perspectives on the Science article:
Miller DM, Patel VA, Sondak VK, et al. Evolving Standards for Resected High-Risk CSCC: Integrating Insights from C-POST and KEYNOTE-630. Journal of Cutaneous Oncology. 2025;3(2). DOI: 10.59449/joco.2025.09.03.
Persuaded—but still asking what to do with the evidence
C-POST supplied the strongest evidence yet that postoperative PD-1 blockade can reduce recurrence in high-risk resected CSCC. The meeting did not interpret that as a command to treat every eligible patient.
Instead, the discussion sharpened the next questions: Who has enough absolute recurrence risk to justify a year of systemic therapy? When should treatment be moved before surgery? Can radiation ever be safely omitted? And why did two superficially similar adjuvant PD-1 trials produce such different results?
That is exactly the kind of uncertainty a Journal Club should preserve.