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C-POST

Society of Cutaneous Oncology

2025-07-11

July 11, 2025 · SoCO Journal Club

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.

Joint academic–industry Journal Club with Regeneron

Read the NEJM article Read the JoCO Perspective

Meeting 38 unique attendees after reconnects were consolidated

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

Primary article
Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma
Rischin D, Porceddu S, Day F, et al. New England Journal of Medicine. 2025. DOI: 10.1056/NEJMoa2502449.
The signal

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.

Academic–industry conversation

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.

Before the discussion

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.

Prior practice
Had clinicians already recommended adjuvant anti–PD-1?
Yes
64%
No
36%
Published analysis: n = 22 clinicians actively managing CSCC.
Case vignette
Untreated parotid metastasis: where did the room lean?
Immunotherapy-first strategy
68%
Surgery → RT ± ICI
12%
The transcript records the tension this created for equipoise in ongoing neoadjuvant trials.
Implementation
Most common anticipated barriers to adjuvant anti–PD-1
Prefer neoadjuvant ICI
65%
Toxicity concerns
48%
Benefit–risk uncertainty
43%
Multiple selections were allowed; six respondents also selected waiting for recurrence to avoid overtreatment.
Radiation
Could postoperative RT be omitted in favor of cemiplimab?
Comfortable
<⅓
Uncertain / uncomfortable
majority
The published Perspective emphasizes substantial ambivalence; C-POST did not test RT omission.
Question 1
Who was in the room?
Medical Dermatologist
25 %
Advanced Practice Provider
12 %
Medical Oncologist
12 %
Non Clinician Researcher
12 %
Other
12 %
Student Trainee
12 %
Surgical Oncologist
12 %
Question 2
How many high-risk CSCC patients did respondents see each month?
I Am A Clinician But I Do Not Treat Cscc
25 %
1 2
12 %
11 20
12 %
3 5
12 %
6, 0
12 %
Greater Than 20
12 %
I Am Not A Clinician
12 %
Question 3
Prior adjuvant anti–PD-1 use
I Am A Clinician But I Do Not Manage Cscc Patients
50 %
No
25 %
I Am Not A Clinician
12 %
Yes
12 %
Question 4
Preferred management for untreated parotid nodal metastasis
Cemiplimab
25 %
I Am A Clinician But I Do Not Manage Cscc Patients
25 %
I Am Not A Clinician
12 %
Nivo Plus Ipi
12 %
Nivolumab
12 %
Pembrolizumab
12 %
Question 5
Comfort omitting postoperative radiation in favor of adjuvant anti–PD-1
3
25 %
I Am A Clinician But I Do Not Manage Cscc Patients
25 %
1
12 %
2
12 %
4
12 %
I Am Not A Clinician
12 %
Question 6
Anticipated future use: neoadjuvant or adjuvant anti–PD-1?
Decision Based On Response At Pre Surgical Evaluation
50 %
I Am A Clinician But I Do Not Manage Cscc Patients
25 %
I Am Not A Clinician
12 %
Routinely Take To Surgery
12 %
Question 7
Barriers to adjuvant anti–PD-1 use
Preference for neoadjuvant immunotherapy
65%
Toxicity concerns
48%
Uncertainty regarding benefit versus risk
43%
Prefer to wait for recurrence to avoid overtreatment
n=6
Multiple selections were allowed. The published Perspective reports the three leading percentages; the meeting transcript additionally records six selections for waiting until recurrence.
What the room wrestled with

The discussion moved beyond the headline result

Radiation became the practical fault line.

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.

Neoadjuvant therapy had already changed the baseline.

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.

C-POST versus KEYNOTE-630 was treated as an inference problem, not a horse race.

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.

The Regeneron perspective added useful restraint.

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.

People in the room

A multidisciplinary meeting

The attendance export contains 38 unique attendees after duplicate reconnects were consolidated, including 9 Regeneron participants. The meeting mixed dermatology, Mohs surgery, surgical oncology, medical oncology, radiation-oriented perspectives, trainees, researchers, and clinical-development colleagues.

Name Attendance Meeting role
Miller, David M. 130 min Academic / clinical
Czapla, Juliane Andrade 101 min Academic / clinical
Christopher Zajac 99 min Regeneron
Adewunmi Adelaja 98 min Academic / clinical
Sarah Nia 97 min Regeneron
Garman, Khalid 97 min Academic / clinical
Matthew Fury 96 min Regeneron
Brownell, Isaac 96 min Academic / clinical
Drews, Reed E 96 min Academic / clinical
Merkin, Ross D. 95 min Academic / clinical
Rubin, Krista M. 95 min Academic / clinical
Kim Premo 95 min Regeneron
Brian Burleson 95 min Regeneron
Suzanne Topalian 93 min Academic / clinical
Gupta, Sameer G. 93 min Academic / clinical
Sondak, Vernon K 92 min Academic / clinical
Kaufman, Howard L. 92 min Academic / clinical
Frank Seebach 91 min Regeneron
Tchekmedyian, Vatche 90 min Academic / clinical
Emerick, Kevin S. 89 min Academic / clinical
Alyson Baryiames 88 min Regeneron
Nikhil Khushalani 88 min Academic / clinical
Andy Knight 80 min Academic / clinical
Stump, Madeliene 78 min Academic / clinical
Julie Montiel 76 min Regeneron
Yancovitz, Molly 74 min Academic / clinical
David Kremer 74 min Regeneron
Vishal Patel 60 min Academic / clinical
O’Loughlin, Lauren 60 min Academic / clinical
Paul Nghiem 60 min Academic / clinical
Ade Adamson 53 min Academic / clinical
Desimone, Jennifer 53 min Academic / clinical
Geskin, Larisa 53 min Academic / clinical
Khaddour, Karam 46 min Academic / clinical
Ferris, Laura 42 min Academic / clinical
Gabriella Chefitz 30 min Academic / clinical
Mariam 4 min Academic / clinical
Montazeri, Kamaneh 1 min Academic / clinical
A few contributions that shifted the discussion

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.

What happened next?

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.

Read the Perspective Open DOI

Where the meeting landed

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.

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