Metastatic or locally advanced cSCC not amenable to curative surgery or radiotherapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV, 30-minute infusion | Day 1 every 3 weeks |
Per the FDA label; evidence:.
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. N Engl J Med. 2018. 379:341-351
- Study type
- Clinical trial
- Design
- Combined report of the expansion cohorts of a phase 1 study for patients with locally advanced or metastatic disease and of the pivotal phase 2 study for a cohort of patients with metastatic disease; in both studies all patients received cemiplimab.
- Sample size
- 26 patients in the phase 1 expansion cohorts and 59 patients in the phase 2 metastatic-disease cohort
- Source
- N Engl J Med · 2018
- Trial registration
- NCT02383212, NCT02760498
In plain words
Cemiplimab is an immunotherapy drug that helps the body's immune system attack cancer cells. In this study, about half of the patients with advanced squamous-cell skin cancer responded to this drug, meaning their tumour shrank. In many of those who responded, the effect lasted. The most common side effects were diarrhoea, tiredness, nausea, constipation and skin rash, and 7% of patients stopped treatment because of side effects.
Key results
13 of 26 patients (50%)
Response rate in the phase 1 expansion cohorts
95% CI 30–70
28 of 59 patients (47%)
Response rate in the phase 2 metastatic-disease cohort (primary endpoint)
95% CI 34–61
7.9 months
Median follow-up in the phase 2 metastatic-disease cohort
57%
Duration of response longer than 6 months (among 28 responders)
82%
Ongoing response and continued cemiplimab at the data cut-off (among 28 responders)
Dose and schedule cards
Cemiplimab in advanced cSCC
Metastatic or locally advanced cSCC not amenable to curative surgery or radiotherapyCycle length: Every 21 daysOn the page “Melanoma (skin cancer)” · Non-melanoma skin cancers: cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1Cemiplimab (in both studies)
Cemiplimab 3 mg/kg IV every 2 weeks (in phase 2 group 1: 8-week cycles for up to 96 weeks, per ClinicalTrials.gov); response was assessed every 8 weeks. Note: the current FDA-approved dose for advanced cSCC is 350 mg IV (30-minute infusion) every 3 weeks until progression, unacceptable toxicity or a maximum of 24 months.
Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT02760498 and the FDA label (LIBTAYO; current approved dose)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with locally advanced or metastatic cutaneous squamous-cell carcinoma for whom surgery or radiotherapy of the lesions was contraindicated; at least one measurable lesion, ECOG 0 or 1 and adequate bone marrow, renal and hepatic function; patients with significant autoimmune disease in the previous 5 years or prior treatment with a PD-1/PD-L1 pathway inhibitor were excluded (ClinicalTrials.gov NCT02760498). In phase 1 the expansion cohorts included locally advanced or metastatic disease, and in phase 2 the metastatic-disease cohort was studied.
Endpoints
The primary endpoint in the phase 2 study was response rate, assessed by independent central review. Duration of response and safety were also reported.
Safety and side effects
In the phase 2 metastatic-disease cohort, adverse events with a frequency of at least 15% included diarrhoea, fatigue, nausea, constipation and rash. 7% of patients discontinued treatment because of an adverse event. The frequency of grade 3 or higher adverse events is not given in the abstract.
Clinical significance and place in guidelines
This study showed that PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma, which previously had no approved systemic therapy, produces a response rate of about 50%. These findings provide the basis for the use of immunotherapy in these patients. The status of drug approvals and clinical guideline recommendations should be checked separately, as the abstract gives no information on them.
Limitations
According to the abstract, all patients in both studies received cemiplimab and no control group is reported. Median follow-up in the phase 2 cohort was short (7.9 months), and survival data are not given in the abstract. Patient numbers in each cohort were relatively small.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.