Cemiplimab plus Chemotherapie NSCLC Stadium III oder IV Erstlinie, EMPOWER-Lung 3

Lungenkarzinom · Version 5.1

A Two-Part Randomized, Phase 3 Study of Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in First-line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NCT03409614)
Short Name Design Population Intervention Comparator Outcomes
EMPOWER-Lung 3
R2810-ONC-16113, 2017-001311-36		 Randomized, Parallel Assignment, Phase 3 quadruple-blind study Treatment-naive with Stage 3-4 and ECOG 0-1 Non-small Cell Lung Cancer 1. REGN2810+Chemo Part 1 (N=0)1
2. REGN2810+AbbrevChemo+ipi (N=0)2
3. Placebo+Chemo (N=154)3
4. Cemiplimab+Chemo (N=312)4
  1. Primary: Overall survival
  2. Secondary: Progression-free survival
  3. Secondary: Objective response rate
  4. Secondary: Duration of Response (DOR)
  5. Secondary: Best overall response (BOR)
  6. Secondary: Incidence of Treatment-emergent adverse events (TEAEs)
  7. Secondary: Incidence of serious adverse events (SAEs)
  8. Secondary: Quality of life as measured by EORTC QLQ-C30
  9. Secondary: Quality of life as measured by EORTC QLQ-LC13
Levels of Evidence
GRADE ⊕⊕⊖⊖a Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
1: Part 1: REGN2810+chemo; 2: Part 1: REGN2810+abbrev chemo+ipi; 3: Part 2: Placebo plus chemo; 4: Part 2: REGN2810+chemo
a: Keine Angaben zur Methodik identifiziert

Outcome Cemiplimab+Chemo N=312 Placebo+Chemo N=154 Effect Estimate GRADE
Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.: Gogishvili, M 2022. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.. ; 28 (11); 2374-2380*
Dichotomous Outcomes
OS - Time To Event N=312 21.9 [15.5; ] N=154 13.0 [11.9; 16.1] HR 0.71 [0.53; 0.93] ⊕⊕⊖⊖
Age
<65 N=184 N=94 HR 0.57 [0.4; 0.81]
>=65 N=128 N=60 HR 0.88 [0.56; 1.37]
Brain Metastases
No N=288 N=147 HR 0.68 [0.51; 0.9]
Yes N=24 N=7 HR 0.42 [0.14; 1.26]
Cancer Stage
Locally Advanced N=45 N=24 HR 0.54 [0.25; 1.15]
Metastatic N=267 N=130 [; ] HR 0.69 [0.51; 0.93]
ECOG PS
0 N=51 N=18 HR 0.55 [0.2; 1.49]
1 N=259 N=134 HR 0.69 [0.52; 0.92]
Histology
Nonsquamous N=179 87 [; ] HR 0.79 [0.54; 1.14]
Squamous N=133 N=67 HR 0.56 [0.37; 0.84]
PD-L1 Level
<1% N=95 N=44 HR 1.01 [0.64; 1.6]
>=50% N=103 N=49 HR 0.61 [0.37; 1.02]
1-49% N=114 N=61 HR 0.52 [0.32; 0.83]
Race
Non-white N=45 N=16 HR 0.79 [0.31; 2.02]
White N=267 N=138 HR 0.67 [0.5; 0.89]
Region
Asia N=42 N=16 HR 0.72 [0.27; 1.88]
Europe N=270 N=138 HR 0.67 [0.5; 0.9]
Sex
Female N=44 N=31 HR 2.11 [0.89; 5.03]
Male N=268 N=123 HR 0.55 [0.41; 0.74]
Smoking
Never Smokers N=43 N=24 HR 1.28 [0.53; 3.08]
Smokers N=269 N=130 HR 0.61 [0.46; 0.82]
PFS - Time To Event N=312 8.2 [6.4; 9.3] N=154 5.0 [4.3; 6.2] HR 0.56 [0.44; 0.7] ⊕⊖⊖⊖a
Brain Metastases
No N=288 N=147 HR 0.54 [0.43; 0.69]
Yes N=24 N=7 HR 0.53 [0.22; 1.31]
PD-L1 Level
<1% N=95 N=44 HR 0.76 [0.51; 1.15]
>=50% N=103 N=49 HR 0.47 [0.31; 0.72]
1-49% N=114 N=61 HR 0.47 [0.33; 0.68]
Race
Non-white N=45 N=16 HR 0.58 [0.28; 1.2]
White N=267 N=138 HR 0.54 [0.43; 0.69]
Region
Asia N=42 N=16 HR 0.52 [0.25; 1.1]
Europe N=270 N=138 HR 0.55 [0.43; 0.7]
Sex
Female N=44 N=31 HR 0.9 [0.5; 1.62]
Male N=268 [; ] N=123 HR 0.48 [0.37; 0.61]
Smoking
Never Smokers N=43 N=24 HR 0.65 [0.34; 1.22]
Smokers N=269 N=130 HR 0.53 [0.42; 0.68]
DOR - Time To Event N=312 15.6 [12.4; ] N=154 7.3 [4.3; 12.6] ⊕⊖⊖⊖b
ORR - TuDD N=312 135 (43.27%) N=154 35 (22.73%) RR 1.9 [1.386; 2.616]; p=0.0001 ⊕⊕⊖⊖
Brain Metastases
No N=288 130 (45.1389%) N=147 33 (22.449%) RR 2.01 [1.451; 2.787]; p=0.0000
Yes N=24 5 (20.8333%) N=7 2 (28.5714%) RR 0.73 [0.179; 2.978]; p=0.6600
Cancer Stage
Locally Advanced N=45 26 (57.7778%) N=24 8 (33.3333%) RR 1.73 [0.934; 3.217]; p=0.0813
Metastatic N=267 109 (40.824%) N=130 27 (20.7692%) RR 1.97 [1.364; 2.833]; p=0.0003
PD-L1 Level
<1% N=95 31 (32.9787%) N=44 10 (22.7273%) RR 1.44 [0.775; 2.66]; p=0.2503
>=50% N=103 55 (53.3981%) N=49 13 (26.5306%) RR 2.01 [1.221; 3.317]; p=0.0061
1-49% N=114 49 (42.9825%) N=61 12 (19.6721%) RR 2.18 [1.261; 3.785]; p=0.0053
Race
Non-White N=45 20 (44.4444%) N=16 4 (25%) RR 1.78 [0.716; 4.414]; p=0.2150
White N=267 115 (43.0712%) N=138 31 (22.4638%) RR 1.92 [1.366; 2.692]; p=0.0002
Sex
Female N=44 19 (43.1818%) N=31 11 (35.4839%) RR 1.22 [0.679; 2.181]; p=0.5094
Male N=268 116 (43.2836%) N=123 24 (19.5122%) RR 2.22 [1.511; 3.257]; p=0.0000
Smoking
Never Smokers N=43 19 (44.186%) N=24 6 (25%) RR 1.77 [0.818; 3.818]; p=0.1472
Smokers N=269 116 (43.1227%) N=130 29 (22.3077%) RR 1.93 [1.364; 2.74]; p=0.0002
TTR - TTE N=312 2.1 [2; 2.3] N=154 2.1 [2.1; 3.9] ⊕⊖⊖⊖b
AE (Any) N=312 299 (95.83%) N=153 144 (94.12%) RR 1.02 [0.973; 1.066]; p=0.4402 ⊕⊕⊖⊖
AE (CTCAE ≥3) N=312 136 (43.59%) N=153 48 (31.37%) RR 1.39 [1.065; 1.813]; p=0.0155 ⊕⊕⊖⊖
AE-D (Any) N=312 19 (6.09%) N=153 12 (7.84%) RR 0.78 [0.387; 1.558]; p=0.4763 ⊕⊕⊖⊖
AE-D (CTCAE ≥3) N=312 19 (6.09%) N=154 12 (7.79%) RR 0.78 [0.389; 1.568]; p=0.4878 ⊕⊕⊖⊖
AE-Disc (Any) N=312 16 (5.13%) N=153 4 (2.61%) RR 1.96 [0.667; 5.767]; p=0.2208 ⊕⊕⊖⊖
AE-Disc (CTCAE ≥3) N=312 13 (4.17%) N=153 4 (2.61%) RR 1.59 [0.528; 4.806]; p=0.4079 ⊕⊕⊖⊖
*Database cutoff: 14.06.2021
a: Fehlende Einzelauswertung der Komponenten des zusammengesetzten Endpunktes (Progression); b: Keine Effektschätzer berichtet
AE: Adverse Events; AE-D: Adverse Events Leading to Death; AE-Disc: Adverse Events Leading to Treatment Discontinuation; Any: Any Grade; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; DOR: Duration Of Response; ORR: Objective Response Rate; OS: Overall Survival; PFS: Progression-Free Survival; TTE: Time To Event ; TTR: Time To Response; TuDD: Time to Definitive Deterioration
Outcome Cemiplimab+Chemo N=312 Placebo+Chemo N=154 Effect Estimate GRADE
Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.: Gogishvili, M 2022. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial.. ; 28 (11); 2374-2380*
Continuous Outcomes
EORTC QLQ-C30 (Pain) N=312 -4.52 [-6.32; -2.73] N=154 0.46 [-2.42; 3.34] MD -4.98 [-8.36; -1.6]; p=0.004 ⊕⊖⊖⊖a
EORTC QLQ-C30 (Global Health Status) N=312 1.69 (0.2) N=154 1.08 (-1.34) LSMD 0.61 [-2.23; 3.45]; p=0.673 ⊕⊖⊖⊖a
*Database cutoff: 14.06.2021
a: Unklare Endpunktdefinition
EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; Global Health Status: Global Health Status; Pain: Pain