Nivolumab plus Ipilimumab neoadjuvant, Evidenzprofil_Checkmate 816

Lungenkarzinom · Version 5.1

Randomized, OpenLabel, Phase 3 Trial of Nivolumab Plus Ipilimumab or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Early Stage NSCLC (NCT02998528)
Short Name Design Population Intervention Comparator Outcomes
CheckMate 816
CA209-816, 2016-003536-21		 Randomized, Parallel Assignment, Phase 3 Open Label study Patients with Stage 1-2 and ECOG 0-1 Non Small Cell Lung Cancer 1. Nivolumab plus platinum doublet chemotherapy (N=179)1
2. Nivolumab plus Ipilimumab (N=0)2		 Platinum doublet chemotherapy (N=179)3
  1. Primary: Event-Free Survival
  2. Primary: Pathological Complete Response
  3. Secondary: Overall survival
Levels of Evidence
GRADE ⊕⊕⊖⊖a,b Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
1: Specified dose on specified days; 2: Specified dose on specified days
a: Open Label Study;b: Missing Patient Flow

Outcome Nivolumab plus platinum doublet chemotherapy
N=179		 Platinum doublet chemotherapy
N=179		 Effect Estimate GRADE
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.: Forde, PM 2022. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.. ; 386 (21); 1973-1985*
Dichotomous Outcomes
EFS - None N=179 31.6 [30.2; ] N=179 20.8 [14; 26.7] HR 0.63 [0.45; 0.87] ⊕⊖⊖⊖a
Age
<65 [31.6; ] 20.8 [14; ] HR 0.57 [0.35; 0.93]
Š≥65 30.2 [23.4; ] 18.4 [10.6; 31.8] HR 0.7 [0.45; 1.08]
Disease stage at baseline
IB or II [27.8; ] [16.8; ] HR 0.87 [0.48; 1.56]
IIIA 31.6 [26.6; ] 15.7 [10.8; 22.7] HR 0.54 [0.37; 0.8]
ECOG performance-status score
0 [30.2; ] 22.7 [16.6; ] HR 0.61 [0.41; 0.91]
1 30.5 [14.6; ] 14.0 [9.8; 26.2] HR 0.71 [0.41; 1.21]
Geographic region
Asia [30.2; ] 16.5 [10.8; 22.7] HR 0.45 [0.29; 0.71]
Europe 31.6 [13.4; ] 21.1 [10.2; ] HR 0.8 [0.36; 1.77]
North America [25.1; ] [12.8; ] HR 0.78 [0.38; 1.62]
Histologic type of tumor
Nonsquamous [27.8; ] 19.6 [13.8; 26.2] HR 0.5 [0.32; 0.79]
Squamous 30.6 [20; ] 22.7 [11.5; ] HR 0.77 [0.49; 1.22]
PD-L1 expression
< 1% 25.1 [; ] 18.4 [; ] HR 0.85 [0.54; 1.32]
≥ 1% [; ] 21.1 [; ] HR 0.41 [0.24; 0.7]
≥50 % [; ] 19.6 [8.2; ] HR 0.24 [0.1; 0.61]
1-49 % [27.8; ] 26.7 [11.5; ] HR 0.58 [0.3; 1.12]
Sex
Female [30.5; ] 31.8 [13.9; ] HR 0.46 [0.22; 0.96]
Male 30.6 [20; ] 16.9 [13.8; 24.9] HR 0.68 [0.47; 0.98]
Smoking status
Current or former smoker 31.6 [30.2; ] 22.4 [15.7; ] HR 0.68 [0.48; 0.96]
Never smoker [5.6; ] 10.4 [7.7; 20.8] HR 0.33 [0.13; 0.87]
TMB
<12.3 mutations/megabase 30.5 [19.4; ] 26.7 [16.6; ] HR 0.86 [0.47; 1.57]
≥12.3 mutations/megabase [14.8; ] 22.4 [13.4; ] HR 0.69 [0.33; 1.46]
Type of platinum therapy
Carboplatin [30.5; ] 10.6 [7.6; 26.7] HR 0.31 [0.14; 0.67]
Cisplatin [25.1; ] 20.9 [15.7; ] HR 0.71 [0.49; 1.03]
OS - Time To Event N=179 [; ] N=179 [; ] HR 0.57 [0.3; 1.07]; p=0.008 ⊕⊕⊖⊖
pCR - None N=179 43 (24.02%) N=179 4 (2.23%) OR 13.83 [4.847; 39.481]; p=0.0000 ⊕⊕⊖⊖
AE (Any) N=176 163 (92.61%) N=176 171 (97.16%) RR 0.95 [0.908; 1.001]; p=0.0542 ⊕⊕⊖⊖
AE (CTCAE ≥3) N=176 72 (40.91%) N=176 77 (43.75%) RR 0.94 [0.733; 1.194]; p=0.5898 ⊕⊕⊖⊖
AE-Disc (Any) N=176 18 (10.23%) N=176 20 (11.36%) RR 0.9 [0.493; 1.642]; p=0.7314 ⊕⊕⊖⊖
AE-Disc (CTCAE ≥3) N=176 10 (5.68%) N=176 7 (3.98%) RR 1.43 [0.556; 3.668]; p=0.4585 ⊕⊕⊖⊖
SAE (Any) N=176 30 (17.05%) N=176 24 (13.64%) RR 1.25 [0.762; 2.049]; p=0.3764 ⊕⊕⊖⊖
SAE (CTCAE ≥3) N=176 19 (10.8%) N=176 17 (9.66%) RR 1.12 [0.601; 2.078]; p=0.7252 ⊕⊕⊖⊖
TAE (CTCAE ≥3) N=176 59 (33.52%) N=176 65 (36.93%) RR 0.91 [0.683; 1.206]; p=0.5036 ⊕⊕⊖⊖
TAE (Any) N=176 145 (82.39%) N=176 156 (88.64%) RR 0.93 [0.853; 1.013]; p=0.0972 ⊕⊕⊖⊖
TAE-D (Any) N=176 0 (0%) N=176 3 (1.7%) RR 0.14 [0.007; 2.746]; p=0.1969 ⊕⊕⊖⊖
TAE-Disc (Any) N=176 18 (10.23%) N=176 17 (9.66%) RR 1.06 [0.564; 1.986]; p=0.8587 ⊕⊕⊖⊖
TAE-Disc (CTCAE ≥3) N=176 10 (5.68%) N=176 6 (3.41%) RR 1.67 [0.619; 4.487]; p=0.3120 ⊕⊕⊖⊖
TSAE (Any) N=176 21 (11.93%) N=176 18 (10.23%) RR 1.17 [0.644; 2.113]; p=0.6109 ⊕⊕⊖⊖
TSAE (CTCAE ≥3) N=176 15 (8.52%) N=176 14 (7.95%) RR 1.07 [0.533; 2.153]; p=0.8463 ⊕⊕⊖⊖
*Database cutoff: not reported
a: Missing individual analysis of combined endpoint componenets (event)
AE: Adverse Events; AE-Disc: Adverse Events Leading to Treatment Discontinuation; Any: Any Grade; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; EFS: Event-Free Survival; OS: Overall Survival; pCR: Pathological Complete Response; SAE: Serious Adverse Events; TAE: Treatment-related Adverse Events; TAE-D: Treatment-related Adverse Events Leading to Death; TAE-Disc: Treatment-related Adverse Events Leading to Treatment Discontinuation; TSAE: Treatment-related Serious Adverse Events