References
1. Mills KC et al. Arch Dermatol. 2012;148:1422–1423. 

2. Ahmed SR et al. Expert Rev Clin Pharmacol. 2019;12:947–951. 

3. Migden MR et al. N Engl J Med. 2018;379:341–351. 

4. Rischin D et al. Ann Oncol. 2019;30(suppl):536–537. 

5. Migden MR et al. J Clin Oncol. 2019;37(suppl):6015. 

6. Migden MR et al. Lancet Oncol. 2020;21:294–305. 

7. Eisenhauer et al. Eur J Cancer. 2009;45:228–247. 

8. Aaronson NK et al. J Natl Cancer Inst. 1993;85:365–376. 

9. Osoba D et al. J Clin Oncol. 1998;16:139–144.

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 Jenna 
Lee, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.

For any questions regarding this poster presentation, please contact Dr Michael R Migden, mrmigden@mdanderson.org

Disclosures
Michael R. Migden: 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. Danny Rischin: 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. Stacie Hudgens: consulting fees from Regeneron Pharmaceuticals, Inc. Chrysalyne D. Schmults: 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. Anna C. Pavlick: 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 
and travel, accommodation, expenses from Regeneron Pharmaceuticals, Inc., Array and Seattle Genetics. Alexander Guminski: 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. Axel Hauschild: 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. Chieh-I Chen,  
Zhen Chen, Vera Mastey, Matthew G. Fury, Israel Lowy, Siyu Li: employees and shareholders of Regeneron Pharmaceuticals, Inc. Anne Lynn S. Chang: 
consulting and advisory roles at Regeneron Pharmaceuticals, Inc. and Merck; research funding from Regeneron Pharmaceuticals, Inc., Novartis, Galderma 
and Merck. Guilherme Rabinowits: consulting and advisory roles for EMD Serono Pfizer, Sanofi, Regeneron Pharmaceuticals Inc. and Merck and Castle and 
stock/other ownership interests from Syros Pharmaceuticals and Regeneron Pharmaceuticals, Inc. Sherrif Ibrahim: research funding from Regeneron 
Pharmaceuticals, Inc. and Castle, speakers’ bureau from Genentech and travel and accommodation expenses from Regeneron Pharmaceuticals, Inc. and 
Genentech. Denise Bury, Medha Sasane: employees and shareholders of Sanofi.

Summary and Conclusion
• These results support cemiplimab as a standard of care option for treatment of 

advanced CSCC, with clinically meaningful benefits on HRQoL and clinically 
meaningful reductions in pain that appear to be independent of opioid use and 
may correlate with tumor response.

Synopsis
• Patients with advanced cutaneous squamous cell carcinoma (CSCC) who are not 

curable by surgery are generally administered palliative systemic therapy.

 - In these patients, pain is an important symptom from the patient and clinician 
perspectives.1

• Cemiplimab is indicated for treatment of patients with metastatic CSCC (mCSCC) or 
locally advanced CSCC (laCSCC) not eligible for curative surgery/radiation.2

• Cemiplimab demonstrated a robust clinical response and a safety profile consistent 
with other checkpoint inhibitors.3

• A Phase 2 clinical trial supported durability of response and reported an overall 
objective response rate (ORR) of 46.1%4-6 as measured by Response Evaluation 
Criteria in Solid Tumors version 1.1 (RECIST 1.1).7

• The Phase 2 trial included the cancer-specific European Organisation for Research 
and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30)8 as a measure  
of patient-reported health-related quality of life (HRQoL).

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/HRQoL

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

Cemiplimab Improves Health-Related Quality of Life (HRQoL) and Reduces Pain in Patients with 
Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Results from a 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 Stacie Hudgens,10 Anne Lynn S. Chang,11  

Guilherme Rabinowits,12 Sherrif Ibrahim,13 Matthew G. Fury,4 Israel Lowy,4 Siyu Li,14 Chieh-I Chen4

1University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Peter MacCallum Cancer Centre, Melbourne, Australia; 3Sanofi, Bridgewater Township, NJ, USA; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 5New York University Langone Medical Center, New York, NY, USA;  
6Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 7Royal North Shore Hospital, Sydney, Australia; 8Schleswig-Holstein University Hospital, Kiel, Germany; 9Sanofi, Cambridge, MA, USA; 10Clinical Outcomes Solutions, Tucson, AZ, USA;  

11Stanford University School of Medicine, Redwood City, CA, USA; 12Miami Cancer Institute/Baptist Health South Florida, Miami, FL, USA; 13Rochester Medical Center, Rochester, NY, USA; 14Regeneron 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.

• Clinically meaningful improvement or stability was experienced by 77%–86% of 
patients across QLQ-C30 scales by cycle 6, and by 74%–95% at cycle 12 (Figure 1).

Presented at the 2021 Winter Clinical Dermatology Conference, January 15–20, 2021, Virtual Scientific Meeting. 

*P<0.0001 vs baseline
10

5

0

−5

−10

−15

−20

−25
Baseline 2 3 4 5 6 7 8 9 10 11 12

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 ±
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Cycle (day 1)

137 125 105 105 101 84 73 65 59 52 43N=152Total

57 47 35 33 29 25 23 18 15 12 7n=67Clinical non-responders

80 78 70 72 72 59 50 47 44 40 36n=85Clinicalresponder

Total Clinical responders Clinical non-responders

0 0.0

−2.7

−8.0*

−13.0*

−8.3

−11.5*

−14.7*

−1.7

−9.7*

−14.9*

−8.1

−12.1*

−15.0*

−0.22

−10.7*

−15.8*

−1.3

−13.4*

−18.9*

−8.6

−16.3*

−19.9*

0.4

−13.8*

−19.9*

−0.9

−13.6*

−18.7*

−9.5

−18.2*

−21.7*

0.1

−14.3*

−18.3*

Figure 2. Change from baseline in QLQ-C30 pain score by cycle among patients 
who had baseline and post-baseline assessment of the QLQ-C30 pain scale

Horizontal broken line indicates threshold for a clinically meaningful change.

140

130

120

110

100

90
2 3 4 5 6 7 8 9 10 11 12

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±

 9
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%

 C
I

Clinical responders (n=85)Total (N=152)

Cycle (day 1)

126.7

117.7

120.0

110.7

114.8

107.7

110.7

101.2

111.6

102.8

112.6

105.1

110.7

100.1

110.3

98.5

110.2

97.4

109.8

96.2

109.5

95.1

Figure 3. Cumulative number of days on opioids over time among patients who had 
baseline and post-baseline assessment of the QLQ-C30 pain scale

CI, confidence interval.

1.0

0.8

0.6

0.4

0.2

0

K
M

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Time to response (week)

+ Censored
A) Clinically meaningful improvement (n=100)

1.0

0.8

0.6

0.4

0.2

0P
ro

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l 
re

s
p

o
n

s
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Time to response (week)
1 15 30 45 60 75 90 105

B) First tumor response (n=85)

1 15 30 45 60 75 90 105

Figure 4. KM survival analysis of time to first clinically meaningful improvement in 
pain score (A) and first tumor response (B)

Time point where horizontal broken line (50% survival probability) crosses curve indicates median time to response.

A) Clinically meaningful deterioration (n=142)

1.0

0.8

0.6

0.4

0.2

0

P
ro

b
a

b
ili

ty
 o

f 
P

F
S

Time to response (week)
1 15 30 45 60 75 90 105 120 135 150 165

B) PFS (n=193)

1.0

0.8

0.6

0.4

0.2

0

K
M

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s
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Time to response (week)

+ Censored

1 15 30 45 60 75 90 105 120 135 150 165

Figure 5. KM survival analysis of time to first clinically meaningful deterioration in 
pain score (A) and PFS (B)

Time point where horizontal broken line (50% survival probability) crosses curve indicates median time to response.

Table 3. Summary of relationship between clinically meaningful changes in pain and 
clinical response among patients with CSCC treated with cemiplimab* 

Clinical 
responders 
(complete + 

partial)

Clinical non-
responders 

(stable + 
progressive) All

Baseline pain score, mean ± SD (n) 26.5 ± 29.1 (85) 33.7 ± 31.1 (83) 30.1 ± 30.3 (168)
Change from baseline in pain score  
at first tumor response, n

85 67 —

LS mean change ± SE –15.2 ± 1.5† –3.9 ± 2.1 —
LS mean (95% CI) difference vs  
non-responders 

–11.3
(–16.3, –6.3)‡

— —

Median time to clinical response, months (n) 2.0 (85) — —

Median PFS, months (n) — — 18.4 (193)
Median time to first pain improvement, 
months (n)

2.1 (53) — 2.1 (100)

Median time to first pain deterioration, 
months (n)

20.6 (80) — 14.8 (142)

*Ns reflect the number of patients who had baseline and post-baseline assessment scores on the QLQ-C30 pain scale.  
†P<0.0001 relative to baseline; ‡P<0.0001 compared with non-responders.

• Since pain medication use was captured over treatment duration, opioids were 
analyzed at each cycle.

 - Opioid use was adjusted for duration to calculate cumulative number of days on 
opioids per patient-year using Poisson regression with treatment group as fixed 
factors and patients’ treatment exposure duration as offset variable.

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/HRQoL 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.

• Baseline scores indicated moderate to high levels of functioning and moderate to low 
symptom burden (Table 2).

• At cycle 3, significant improvements from baseline were observed for emotional and 
social function and symptoms of pain, insomnia, appetite loss, nausea/vomiting,  
and constipation (all P<0.05) (Table 2).

• Improvements increased or were maintained at cycle 12 and were clinically 
meaningful for pain, insomnia, appetite loss, and constipation (Table 2).

• These improvements likely contributed to the improved HRQoL that was significant at 
cycle 3 (P<0.001) and clinically meaningful at cycle 12.

• In all patients, reductions from baseline in pain were statistically significant as early as 
cycle 2, clinically meaningful by cycle 3, and sustained to cycle 12 (Figure 2).

• In contrast to clinical non-responders, clinical responders reported a clinically 
meaningful reduction in pain from baseline at cycle 2 with further reductions that were 
sustained to cycle 12 (all P<0.0001) (Figure 2).

• Opioid use decreased over study duration (Figure 3), suggesting that clinically 
meaningful improvement in pain was independent of opioid use.

• Median time to first clinically meaningful pain improvement in all patients 
approximated the median time to first tumor response that was estimated for clinical 
responders, 2.0 months and 2.1 months, respectively (Figure 4; Table 3).

 - Among clinical responders, the median time to first clinically meaningful pain 
improvement was also 2.1 months.

• The change from baseline in pain score at first tumor response was statistically 
significant and clinically meaningful versus non-responders (P<0.0001) (Table 3).

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

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

• Median time to first clinically meaningful deterioration in pain approximated the median 
time to progression-free survival (PFS), 14.8 months and 18.4 months, respectively 
(Figure 5; Table 3).

 - Median time to first clinically meaningful pain deterioration among clinical 
responders was 20.6 months (Table 3).

Objective
• This post hoc analysis explored the effects of cemiplimab on HRQoL and pain using 

QLQ-C30 data from the Phase 2 clinical trial (NCT02760498) of advanced CSCC, with 
a focus on the association between time to clinically meaningful changes in pain and 
clinical tumor response.

Methods
• For inclusion in this non-randomized, global, pivotal trial, adults with advanced CSCC 

not amenable to curative surgery/radiotherapy according to the investigator were  
required to have ≥1 lesion, Eastern Cooperative Oncology Group (ECOG) performance  
status ≤1, and life expectancy >12 weeks.

• Patients (N=193) received intravenous 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 the Q2W groups and 9 weeks for the  
Q3W group.

• The QLQ-C308 was administered at baseline and day 1 of each treatment cycle. 

• The QLQ-C30 assesses HRQoL over the past week using a Global Health Status/
HRQoL scale and across functional domains (physical, role, cognitive, emotional,  
and social functioning) and symptoms (fatigue, pain, nausea/vomiting, dyspnea, 
insomnia, appetite loss, constipation, diarrhea, and financial difficulties).

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

 - A change ≥10 points from baseline is considered clinically meaningful.9

• Mixed-effects repeated measures models (MMRM) estimated changes from baseline 
to each cycle on all QLQ-C30 scales; results are expressed as least squares (LS) 
mean and standard error (SE).

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

• Changes from baseline in pain were also stratified by clinical responders, defined by 
ORR assessed by independent central review, and clinical non-responders (stable or 
progressive disease).

• For patients with data from baseline to cycle 6 and cycle 12, proportions with 
clinically meaningful (≥10 points) improvement or worsening, or stability (<10 points) 
on each item was determined.

• Kaplan–Meier (KM) survival analysis was used to estimate time to first clinically 
meaningful change in QLQ-C30 pain score and its relationship to tumor response  
in patients who had baseline pain scores that allowed for at least a 10-point change.

Results
• Demographic characteristics of enrolled patients (N=193) were generally similar 

across treatment groups (Table 1).