The evidence supporting this protocol is provided by a phase 3 multicentre, open-label, international randomised trial (EMPOWER-Lung 1) involving 712 patients comparing cemiplimab monotherapy with investigator’s choice platinum-doublet chemotherapy in patients with confirmed squamous or non-squamous locally advanced (not suitable for surgery or definitive chemoradiation) or metastatic non-small cell lung cancer with PD-L1 tumour expression of 50% or more and no EGFR mutations, ALK translocations, or ROS1 fusions.4
Between May 2017 and March 2020, 357 patients were randomised to receive cemiplimab 350 mg intravenously every 3 weeks (up to 36 treatment cycles) and 355 patients were randomised to receive investigator’s choice platinum doublet chemotherapy (maintenance pemetrexed permitted as per standard of care). Randomisation was stratified by tumour histology. Crossover was allowed.4, 5
The primary end point was overall survival (OS) and progression-free survival (PFS) and secondary end points were objective response rate (ORR), duration of response (DoR), health related quality of life (HRQoL) and safety.4
Efficacy
At 35 months follow up (two years after the primary analysis) in the PD-L1 ≥ 50% population, the median OS in the cemiplimab group was 26.1 months (95% CI, 22.1–31.8) and 13.3 months (10.5–16.2) in the chemotherapy group (hazard ratio [HR] 0.57, 95% CI, 0.46–0.71; p<0.0001). The median PFS was 8.1 months (95% CI, 6.2–8.8) in the cemiplimab group compared to 5.3 months (95% CI, 4.3–6.1) in the chemotherapy group (HR 0.51, 95% CI, 0.42–0.62; p<0.0001). The subgroup analysis for OS and PFS showed improved survival across all subgroups in patients receiving cemiplimab.5
Kaplan Meier curve of OS and PFS in the PD-L1 ≥ 50% population5


© Lancet Oncol 2023
Response rates in patients with PD-L1 tumour expression ≥ 50%5
|
Cemiplimab monotherapy
(n= 284) |
Chemotherapy
(n=281) |
Objective response rate (ORR) % (95% CI) |
46 (41–53) |
21 (16–26) |
Complete response (CR), n (%) |
23 (8) |
6(2) |
Partial response (PR), n (%) |
109 (38) |
53 (19) |
Median duration of response (DoR), months (95% CI) |
23.6 (16.8–33.0) |
5.9 (4.3–6.5) |
It was generally observed that a higher PD-L1 expression was associated with increased ORR and median OS and PFS in patients treated with cemiplimab. These benefits have been observed despite a high crossover rate. Similar effects were observed in the full intention-to-treat (ITT) population.5
HRQoL data was collected and showed only modest improvement in the cemiplimab group and no clinically meaningful change in the chemotherapy group.4
Toxicity
Treatment-related adverse events (TRAE) occurred in 57% of patients who received cemiplimab and 89% of patients who received chemotherapy.4
In the cemiplimab group, events leading to death occurred in 9 (3%) patients including autoimmune cardiac events, nephritis and respiratory failure. Overall, immune-related adverse events occurred in 62 (17%) of patients in the cemiplimab group.
In the updated analysis at 35 months, despite the considerably longer exposure to cemiplimab, the safety profile was generally consistent with the primary analysis, with no new safety signals observed.5
Most common treatment-related adverse events4
Adverse event |
All grades |
Grade 3-4 |
|
Cemiplimab n=355 |
Chemotherapy n=342 |
Cemiplimab n=355 |
Chemotherapy n=342 |
Any |
204 (57%) |
303 (89%) |
41 (11%) |
127 (37%) |
Increased transaminases |
43 (12%) |
24 (7%) |
8 (2%) |
1 (<1%) |
Decreased appetite |
18 (5%) |
49 (14%) |
1 (<1%) |
1 (<1%) |
Anaemia |
18 (6%) |
152 (45%) |
2 (1%) |
51 (15%) |
Rash |
18 (5%) |
8 (2%) |
3 (1%) |
0 |
Diarrhoea |
15 (4%) |
23 (7%) |
1 (<1%) |
6 (2%) |
Arthralgia |
13 (4%) |
21 (6%) |
0 |
1 (<1%) |
Fatigue |
15 (4%) |
42 (12%) |
3 (1%) |
4 (1%) |
Nausea/vomiting |
25 (7%) |
136 (39%) |
0 |
8 (2%) |
Increased amylase |
11 (3%) |
2 (<1%) |
1 (<1%) |
1 (<1%) |
Pneumonitis |
11 (3%) |
1 (<1%) |
1 (<1%) |
0 |