References
1. Karia PS et al. J Am Acad Dermatol. 2013;68:957–966.
2. Rogers HW et al. JAMA Dermatol. 2015;151:1081–1086.
3. Que SK et al. JAAD. 2018;78:237–247.
4. Ahmed SR et al. Expert Rev Clin Pharmacol. 2019;12:947–951.
5. Migden MR et al. N Engl J Med. 2018;379:341–351.
6. Rischin D et al. Ann Oncol. 2019;30(suppl 5):536–537.
7. Migden MR et al. J Clin Oncol. 2019;37(15 suppl):6015.
8. Migden MR et al. Lancet Oncol. 2020;21:294–305.

9. Aaronson NK et al. J Natl Cancer Inst. 1993;85:365–376.
10. Mills KC et al. Arch Dermatol. 2012;148:1422–1423.
11. Osoba D et al. J Clin Oncol. 1998;16:139–144.
12. Scott NW et al. EORTC QLQ-C30 Reference Values. 2nd ed. Brussels, 

Belgium: EORTC Quality of Life Group. 2008. Available at: www.eortc.org/
app/uploads/sites/2/2018/02/reference_values_manual2008.pdf. 
[Accessed May 1, 2020].

Funding sources
Funding was provided by Regeneron Pharmaceuticals, Inc. and Sanofi.

Acknowledgments
The authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. The study was 
funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Medical writing support was provided by E. Jay Bienen, PhD, and typesetting was provided by Kate 
Carolan, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.
For any questions or comments, please contact Dr Michael R Migden, mrmigden@mdanderson.org

Disclosures
M. R. Migden reports honoraria and travel expenses from Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly, and Sun Pharma; and institutional 
research funding from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Eli Lilly. D. Rischin reports institutional research grant and funding from Regeneron 
Pharmaceuticals, Inc., Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, and GlaxoSmithKline; uncompensated scientific committee and advisory board from 
Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, and Bristol-Myers Squibb; travel and accommodation from Merck Sharp & 
Dohme and GlaxoSmithKline. A. Pavlick reports honoraria and consulting or advisory roles at Bristol-Myers Squibb, Merck, Regeneron Pharmaceuticals, Inc., Array, 
Novartis, Seattle Genetics, and Amgen; research funding from Bristol-Myers Squibb, Merck, Regeneron Pharmaceuticals, Inc., Celldex, and Forance; travel, 
accommodation, and expenses from Regeneron Pharmaceuticals, Inc., Array, and Seattle Genetics. C.D. Schmults is a steering committee member for Castle 
Biosciences; a steering committee member and consultant for Regeneron Pharmaceuticals, Inc.; a consultant for Sanofi; has received research funding from Castle 
Biosciences, Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Merck, and is a chair for the National Comprehensive Cancer Network. A. Guminski reports 
personal fees and non-financial support (advisory board and travel support) from Bristol-Myers Squibb and Sun Pharma; personal fees (advisory board) from Merck 
KGaA, Eisai, and Pfizer; non-financial (travel) support from Astellas; and clinical trial unit support from PPD Australia. A. Hauschild reports institutional grants, 
speaker’s honoraria, and consultancy fees from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche, and Novartis; 
institutional grants and consultancy fees from Merck Serono, Philogen, and Regeneron Pharmaceuticals, Inc.; and consultancy fees from OncoSec.  
A.L.S. Chang reports consulting and advisory roles at Regeneron Pharmaceuticals, Inc. and Merck; research funding from Regeneron Pharmaceuticals, Inc.,  
Novartis, Galderma, and Merck. G. Rabinowits reports consulting and advisory roles for EMD Serono Pfizer, Sanofi, Regeneron Pharmaceuticals Inc., Merck and 
Castle, and stock/other ownership interests from Syros Pharmaceuticals and Regeneron Pharmaceuticals, Inc. S. Ibrahim reports research funding from Regeneron 
Pharmaceuticals, Inc. and Castle, speakers’ bureau from Genentech, and travel and accommodation expenses from Regeneron Pharmaceuticals, Inc. and Genentech. 
M. Sasane, V. Mastey, Z. Chen, D. Bury, I. Lowy, M.G. Fury, S. Li, and C-I Chen are employees and shareholders of Regeneron Pharmaceuticals, Inc.

Summary and Conclusion
• In advanced CSCC patients, treatment with cemiplimab resulted in 

clinically meaningful reduction in pain as early as cycle 3 with 
maintenance of effect through cycle 12.  

• Improvement in global health status/HRQL was observed as early as 
cycle 3 with clinically meaningful improvement seen by cycle 12.

• By cycle 6, the majority of patients experienced clinically meaningful 
improvement or stability in global health status/HRQL and functional 
status, while maintaining a low symptom burden. 

• These results further support cemiplimab as a new standard of care 
option in the treatment of advanced CSCC.

Synopsis
• Cutaneous squamous cell carcinoma (CSCC) is considered the second 

most common malignancy in the US, although its exclusion from national 
cancer registries has presented a barrier to epidemiologic characterization.1

 - Estimates suggest an incidence of around 1.5 million cases per year in 
the US.2

 - The incidence of CSCC is increasing yearly in the US.3

• Most CSCC patients have a favorable prognosis, but for the patients who  
are not amenable to curative surgery, palliative systemic therapy has been 
administered.1

• Cemiplimab is a programmed cell death (PD)-1 inhibitor that is indicated for 
treatment of CSCC in patients with metastatic (mCSCC) or locally advanced 
(laCSCC) disease not amenable to curative surgery or curative radiation.4

 - Cemiplimab demonstrated a robust durable clinical response and a 
safety profile consistent with other checkpoint inhibitors in a recent 
Phase 2 study (NCT02760498).5–8 

 - Longer follow-up data from the Phase 2 study of cemiplimab in patients 
with advanced CSCC is presented in the poster titled “Phase 2 Study  
of Cemiplimab in Patients with Advanced Cutaneous Squamous  
Cell Carcinoma (CSCC): Longer Follow-Up”, also available on the  
2020 Fall Clinical Dermatology Conference platform.

 - No new safety signals emerged with longer follow-up. The most common 
treatment-emergent adverse events of any grade were fatigue (n=67, 
34.7%), diarrhea (n=53, 27.5%), and nausea (n=46, 23.8%).

• The Phase 2 trial included the European Organisation for Research and 
Treatment of Cancer (EORTC) cancer-specific 30-item questionnaire (QLQ-C30)9 
as a measure of patient-reported health-related quality of life (HRQL).

• Pain is an important and bothersome symptom in the diagnosis and 
treatment of CSCC from the patient and clinical perspectives.10

Objective
• This post hoc exploratory analysis examined the QLQ-C30 data from a 

Phase 2 clinical trial (NCT02760498) to determine the effects of cemiplimab 
treatment on HRQL and pain.

Methods
• For inclusion in the Phase 2, non-randomized, global, pivotal trial of 

cemiplimab (Figure 1), adults with invasive CSCC not amenable to curative 
surgery or curative radiotherapy according to the investigator were also 
required to have ≥1 lesion, Eastern Cooperative Oncology Group (ECOG) 
performance status ≤1, and life expectancy >12 weeks.

 - Adult patients (N=193) received intravenous (IV) cemiplimab 3 mg/kg  
every 2 weeks (Q2W; mCSCC n=59; laCSCC n=78) for 12 treatment cycles 
or 350 mg every 3 weeks (Q3W; mCSCC n=56) for six treatment cycles.

 - Treatment cycle length was 8 weeks for Groups 1 and 2 and 9 weeks  
for Group 3.

 - The primary efficacy endpoint was objective response rate, defined as  
the proportion of patients with complete or partial response.

• At baseline and day 1 of each treatment cycle until progression, patients 
were administered the QLQ-C30.9

Group 1 – Adult patients
with metastatic (nodal 
and/or distant) CSCC

Cemiplimab 
3 mg/kg

Q2W IV, for up to 
96 weeks

Cemiplimab 
350 mg/kg

Q3W IV, for up to 
54 weeks

Tumor response assessment by ICR (RECIST v1.1 
for scans; modified WHO criteria for photos)

EORTC QLQ-C30 quality of life questionnaire 
administered at baseline and day 1 of each 

treatment cycle

Tumor imaging
 every 8 weeks 

for the 
assessment 

of clinical activity

Tumor imaging 
every 9 weeks 

for the 
assessment

of clinical activity

Group 3 – Adult patients
with metastatic (nodal 
and/or distant) CSCC

Group 2 – laCSCC

Key inclusion criteria
•  ECOG performance status of 0 or 1
•  Adequate organ function
•  Groups 1 and 3:

-  At least one lesion measurable by RECIST v1.1 
•  Group 2

-  At least one lesion measurable by digital medical 
photography 

-  CSCC lesion that is not amendable to curative 
surgery or curative radiation therapy per investigators’ 
assessment

-  Tumor biopsies at baseline and on day 29, for 
exploratory biomarker analysis, unless considered 
to have unacceptable safety risks by the investigator

Key exclusion criteria
• Ongoing or recent (within 5 years) autoimmune disease 
 requiring systemic immunosuppression
• Prior treatments with anti–PD-1 or anti–PD-L1 therapy
•  History of solid organ transplant, concurrent malignancies 
 (unless indolent or not considered life-threatening; for 
 example, basal cell carcinoma), or hematologic malignancies

Figure 1. Study design

ICR, independent central review; PD-L1, PD-ligand 1; RECIST v1.1, Response Evaluation Criteria In Solid Tumors 
version 1.1; WHO, World Health Organization.

29.8
(30.4)

20.3
(26.9) 13.6

(20.2)

16.0
(23.0) 12.7

(19.5)

14.9
(22.8)

12.5
(21.9) 9.4

(17.6)

12.8
(23.3)

12.7
(22.4) 8.3

(18.2)

12.4
(20.9)

65.1
(22.9)

70.1
(21.6)

75.4
(19.7)

75.8
(19.0)

75.3
(18.4)

73.4
(21.2)

75.1
(21.0)

77.4
(18.5)

75.8
(19.5)

77.8
(16.6)

78.2
(18.8)

77.1
(19.9)

100

80

60

40

20

0

100

80

60

40

20

0
Baseline 2 3 4 5 6 7 8 9 10 11 12

150 136 122 104 104 101 84 73 65 59 52 43

152 137 125 105 105 101 84 73 65 59 52 43

M
e

a
n

 p
a

in
 s

c
o

re
 (

S
D

);
 

lo
w

e
r 

sc
o

re
 =

 b
e

tt
e

r 
o

u
tc

o
m

e

n =

n =

Cycle (day 1)

M
e
a
n

 g
lo

b
a
l h

e
a
lth

 sta
tu

s/H
R

Q
L

 sc
o

re
 

(S
D

); h
ig

h
e
r sc

o
re

 =
 b

e
tte

r o
u

tc
o

m
e

Figure 2. QLQ-C30 pain and global health status/HRQL scores by cycle

23

14

30

40

35

14

56

16

44

47

23

28

28

30

51

60

77

60

53

60

72

28

79

30

30

58

58

49

56

40

16

9

9

7

5

14

16

5

26

23

19

14

23

14

9

Improvement Maintenance Deterioration

Cycle 12 (n=43)

13

7

22

28

31

19

43

11

37

35

23

26

28

23

43

75

88

64

62

51

71

41

78

31

49

55

59

40

56

40

12

5

14

10

18

10

17

11

33

17

22

15

33

21

18

0 20 40 60 80 100

Global health status/HRQL

Physical function

Role function

Emotional function

Cognitive function

Social function

Fatigue

Nausea/vomiting

Pain

Dyspnea

Insomnia

Appetite loss

Constipation

Diarrhea

Financial problems

Patients (%)
0 20 40 60 80 100

Patients (%)

Cycle 6 (n=101)

Figure 3. Proportion of patients reporting clinically meaningful change at 
cycle 6 and cycle 12

Health-Related Quality of Life (HRQL) in Patients with Advanced Cutaneous Squamous 
Cell Carcinoma (CSCC) Treated with Cemiplimab: Post Hoc Exploratory Analysis of a 

Phase 2 Clinical Trial  
Michael R. Migden,1 Danny Rischin,2 Medha Sasane,3 Vera Mastey,4 Anna Pavlick,5 Chrysalyne D. Schmults,6 Zhen Chen,4 Alexander Guminski,7 Axel Hauschild,8 Denise Bury,9 Anne Lynn S. Chang,10 Guilherme Rabinowits,11  

Sherrif Ibrahim,12 Israel Lowy,4 Matthew G. Fury,4 Siyu Li,13 Chieh-I Chen4

 1Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; 3Sanofi, Bridgewater, NJ, USA; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 5Department of Medical Oncology, New York University Langone 
Medical Center, New York, NY, USA; 6Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 7Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia; 8Department of Dermatology, University Hospital (UKSH), Kiel, Germany; 9Sanofi, Cambridge, MA, USA 10Department of Dermatology,  

Stanford University School of Medicine, CA, USA; 11Department of Hematology/Oncology, Miami Cancer Institute/Baptist Health South Florida, Miami, FL, USA; 12Department of Dermatology, Rochester Medical Center, Rochester, NY, USA; 13Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA

Table 1. Demographic and clinical characteristics of the full analysis set

Variable Total
(N=193)

mCSCC 
350 mg 

Q3W (n=56)

mCSCC  
3 mg/kg 

Q2W (n=59)

laCSCC  
3 mg/kg Q2W 

(n=78)

Age, mean ± SD, years 71.1 ± 11.4 69.7 ± 12.8 70.4 ± 10.1 72.5 ± 11.2

≥65 years, n (%) 144 (74.6) 42 (75.0) 43 (72.9) 59 (75.6)

Male, n (%) 161 (83.4) 48 (85.7) 54 (91.5) 59 (75.6)

ECOG performance status, n (%)

0 86 (44.6) 25 (44.6) 23 (39.0) 38 (48.7)

1 107 (55.4) 31 (55.4) 36 (61.0) 40 (51.3)

Primary site, n (%)

Head and neck 131 (67.9) 31 (55.4) 38 (64.4) 62 (79.5)

Other 62 (32.1) 25 (44.6) 21 (35.6) 16 (20.5)

Prior cancer-related 
systemic therapy, n (%)

65 (33.7) 20 (35.7) 33 (55.9) 12 (15.4)

Prior cancer-related 
radiotherapy, n (%)

131 (67.9) 38 (67.9) 50 (84.7) 43 (55.1)

SD, standard deviation.

Table 2. Baseline scores and change from baseline (MMRM) in patients in 
the full analysis set who had baseline and post-baseline assessments on 
each QLQ-C30 scale or item

QLQ-C30 scale/item Baseline, mean 
± SD (n)

LS mean change ± SE (n)

Cycle 3 Cycle 12

Global health status/HRQL 65.1 ± 22.9 (150) 7.8 ± 1.6 (122)** 11.1 ± 2.6 (43)**

Functional scales†

Physical function 80.1 ± 22.8 (151) 1.1 ± 1.3 (124) 4.0 ± 2.1 (43)

Role function 75.8 ± 30.0 (151) 0.4 ± 2.1 (123) 5.6 ± 3.4 (43)

Emotional function 80.2 ± 21.2 (151) 4.2 ± 1.3 (123)* 5.3 ± 2.2 (43)*

Cognitive function 83.4 ± 22.2 (151) 1.7 ± 1.4 (123) 2.5 ± 2.3 (43)

Social function 74.4 ± 31.8 (150) 5.3 ± 1.8 (122)* 8.6 ± 3.0 (43)*

Symptoms‡

Fatigue 30.2 ± 24.6 (152) –2.8 ± 1.7 (125) –4.8 ± 2.8 (43)

Nausea/vomiting 4.6 ± 12.2 (152) –1.6 ± 0.8 (125)* –2.9 ± 1.3 (43)*

Pain 29.8 ± 30.4 (152) –11.5 ± 1.9 (125)** –14.3 ± 3.1 (43)**

Dyspnea 12.9 ± 23.4 (152) 0.7 ± 1.7 (125) 1.5 ± 2.9 (43)

Insomnia 27.4 ± 28.0 (151) –9.1 ± 2.0 (123)** –17.4 ± 3.3 (43)**

Appetite loss 19.5 ± 29.3 (152) –8.4 ± 1.6 (124)** –13.7 ± 2.7 (43)**

Constipation 13.6 ± 24.1 (152) –4.5 ± 1.5 (125)* –11.2 ± 2.5 (43)**

Diarrhea 4.9 ± 13.6 (150) 3.6 ± 1.4 (121)* 0.6 ± 2.3 (43)

Financial difficulty 19.1 ± 30.7 (150) 0.5 ± 2.0 (122) –3.4 ± 3.3 (43)
**P<0.001 and *P<0.05 versus baseline. †Higher scores reflect better outcomes. ‡Lower scores reflect better outcomes.

• The QLQ-C30 assesses HRQL over the past week among cancer patient 
populations using a global health status/HRQL scale, five functional scales, 
and nine symptom scales/items.

 - Functional scales include physical, role, cognitive, emotional, and  
social functioning.

 - Symptom scales/items include fatigue, pain, nausea/vomiting, dyspnea, 
insomnia, appetite loss, constipation, diarrhea, and financial difficulties.

 - Scores range from 0 to 100; high scores on functional scales and low 
scores on symptom scales reflect better outcomes.

 - A change ≥10 points from baseline is considered clinically meaningful.11

• The full analysis set included patients who had baseline and at least one 
post-baseline assessment for any QLQ-C30 scale. 

• Descriptive statistics were used to summarize HRQL scores over time (only 
pain and global health status/HRQL scores are shown).

• Mixed effects repeated measures models (MMRM) were used to estimate 
the mean treatment effect (change from baseline while accounting for 
missing data) for all QLQ-C30 scales.

 - The model included fixed effects of treatment, visit, treatment-by-visit 
interaction, and baseline value of the specified individual item.

 - Results are expressed as the least squares (LS) mean and standard  
error (SE).

• A responder analysis was also conducted at cycle 6 and cycle 12 based  
on evaluation of average change from baseline among patients who had 
baseline scores that allowed a ≥10-point change.

 - A responder was defined as a patient who achieved an average 10-point 
increase in functional scale scores and 10-point decline in symptom 
scale scores.

Results
Patient population and baseline scores
• A total of 193 adult patients were enrolled in the study, and demographic 

characteristics were generally similar across the treatment groups (Table 1).

• Baseline scores for QLQ-C30 indicated generally moderate to high levels of 
functioning and moderate to low symptom burden (Table 2).

 - Pain is of importance as a symptom in patients with advanced CSCC, 
and the baseline pain score of patients with advanced CSCC receiving 
cemiplimab (29.8 ± 30.4) was worse than that reported by patients with 
advanced head and neck cancer (24.9 ± 26.3; n=1722) and the general 
population (20.9 ± 27.6; n=7802) in the literature12; comparisons with  
both groups were significant, P<0.05 and P<0.0001, respectively.

Longitudinal analysis
• Among the symptom scales and items, a marked improvement in pain 

score was observed as early as cycle 2 (Figure 2). The initial clinically 
meaningful improvement (≥10 points) in pain score at cycle 3 (LS mean 
[SE] change –11.5 [1.9]; P<0.0001) was maintained during study treatment 
to cycle 12 (LS mean [SE] change –14.3 [3.1]; P<0.0001) (Table 2).

 - At cycle 3, significant improvements from baseline were also observed 
for symptoms of insomnia, appetite loss, and constipation. At cycle 12, 
these improvements reached the clinically meaningful threshold (Table 2).

 - With the exception of a significant worsening of diarrhea at cycle 3 and  
a significant improvement of nausea/vomiting at cycle 12, all other 
domains/symptoms remained stable relative to baseline. By cycle 12, 
diarrhea remained stable relative to baseline.  

• Among the functional scales, significant improvements were observed in 
emotional and social function at cycle 3 and cycle 12. All other functional 
scales remained stable relative to baseline (Table 2).

• For global health status/HRQL, significant improvement from baseline  
was observed at cycle 3. At cycle 12, this improvement reached the 
clinically meaningful threshold (LS mean [SE] change 11.1 [2.6]; 
P<0.0001) (Table 2).

Responder analysis 
• By cycle 6, the majority of patients experienced clinically meaningful  

(≥10 points) improvement or stability including pain (83%), nausea/vomiting 
(89%), diarrhea (95%), constipation (86%), and appetite loss (90%), 
as well as functional scales (77%–86%) (Figure 3).

 - These effects likely account for the clinically meaningful improvement or 
stability also reported on global health status/HRQL among the majority 
of patients (82%).

• At cycle 12, the majority of patients showed sustained improvement and 
stabilization across all symptoms and functional scales (74%–95%). Ninety-
one percent of patients experienced clinically meaningful improvement or 
stability in global health status/HRQL scores at cycle 12 (Figure 3).

• The proportions of patients with clinically meaningful deterioration were 
generally low at both evaluated time points (Figure 3).

 - The highest rate of clinically relevant deterioration among the symptoms 
was observed for fatigue.

Study Limitations
• This was a non-randomized, single-arm, open-label study.

• The 10-point threshold considered indicative of a clinically meaningful 
change has not been validated for this specific patient population  
(i.e., advanced CSCC).

Presented at the 2020 Fall Clinical Dermatology Conference, October 29–November 1, Virtual Scientific Meeting (encore of ASCO 2020 poster presentation).