Pembrolizumab Erstlinie KEYNOTE-042; Atezolizumab Erstlinie IMpower 110

Lungenkarzinom · Version 5.1

Atezolizumab (Neues Anwendungsgebiet: Nicht-kleinzelliges Lungenkarzinom, PD-L1 Expression ≥ 50 % auf TC oder ≥ 10 % auf IC, EGFR/ALK-negativ, Erstlinie)
Wirkstoff	Atezolizumab	Handelsname	Tecentriq
Pharmazeutischer Unternehmer	Roche Pharma AG	Beschlussdatum	19.11.2021
Anwendungsgebiet	Lungenkarzinom, nicht-kleinzelliges

Population/ZVT	Titel	Mortalität	Morbidiät	QoL	Sicherheit	Zusatznutzen
A	Erwachsene mit metastasiertem, nicht-kleinzelligem Lungenkarzinom (NSCLC), deren Tumore eine PD-L1-Expression ≥ 50 % der Tumorzellen aufweisen und die keine EGFR-Mutationen oder ein ALK-positives NSCLC haben; Erstlinie	↔Kein Unterschied im Gesamtüberleben.	n.b.Es liegen keine bewertbaren Daten vor.	n.b.Es liegen keine bewertbaren Daten vor.	↔Keine für die Nutzenbewertung relevanten Unterschiede.	ist nicht belegt
ZVT	Pembrolizumab als Monotherapie	↔Kein Unterschied im Gesamtüberleben.	n.b.Es liegen keine bewertbaren Daten vor.	n.b.Es liegen keine bewertbaren Daten vor.	↔Keine für die Nutzenbewertung relevanten Unterschiede.	ist nicht belegt
B	Erwachsene mit metastasiertem, nicht-kleinzelligem Lungenkarzinom (NSCLC), deren Tumore eine PD-L1-Expression < 50 % der Tumorzellen und eine PD-L1-Expression ≥ 10 % bei tumorinfiltrierenden Immunzellen aufweisen und die keine EGFR-Mutationen oder ein ALK-positives NSCLC haben; Erstlinie	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ist nicht belegt
ZVT	Cisplatin in Kombination mit einem Drittgenerationszytostatikum (Vinorelbin oder Gemcitabin oder Docetaxel oder Paclitaxel oder Pemetrexed (außer bei überwiegend plattenepithelialer Histologie))oder- Carboplatin in Kombination mit einem Drittgenerationszytostatikum (Vinorelbin oder Gemcitabin oder Docetaxel oder Paclitaxel oder Pemetrexed (außer bei überwiegend plattenepithelialer Histologie)) vgl. Anlage VI zum Abschnitt K der Arzneimittel-Richtlinieoder- Carboplatin in Kombination mit nab-Paclitaxeloder- Pembrolizumab in Kombination mit Pemetrexed und platinhaltiger Chemotherapie (nur für Erwachsene mit nicht-plattenepithelialer Histologie)oder- Pembrolizumab in Kombination mit Carboplatin und entweder Paclitaxel oder nab-Paclitaxel (nur für Erwachsene mit plattenepithelialer Histologie)oder- Monotherapie mit Gemcitabin oder Vinorelbin (nur für Erwachsene mit ECOG Performance-Status 2 als Alternative zur Platin-basierten Kombinationsbehandlung)	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ØEs liegen keine Daten vor.	ist nicht belegt
↑↑/↓↓: positiver/negativer statistisch signifkanter Effekt, hohe Aussagesicherheit; ↑/↓: positiver/negativer statistisch signifkanter Effekt, niedrige oder unklare Aussagesicherheit; ↔: kein signifikanter/relevanter Unterschied; ↓: n.b.: nicht bewertbar; Ø: keine Daten

Short Name	Design	Population	Intervention	Comparator	Outcomes
A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) Versus Platinum Based Chemotherapy in Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042)(NCT02220894)
KEYNOTE-042 3475-042, 2014-001473-14, 152877, MK-3475-042, KEYNOTE-042	Randomized, Parallel Assignment, Phase 3 Open Label study	Treatment-naive with Stage 3-4 and ECOG 0-1 Non-small Cell Lung Cancer	1. Pembrolizumab (N=637)¹	1. SOC Treatment (N=637)²	Primary: Overall Survival Secondary: Progression-Free Survival Secondary: Objective Response Rate Secondary: Adverse Event Secondary: Discontinued Study Treatment Due to an Adverse Event
Levels of Evidence
GRADE	⊕⊕⊕⊖^a	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
1: Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.; 2: Participants receive carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 IV on Day 1 of every 21-day cycle (Q3W) for a maximum of 6 cycles OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 IV on Day 1 Q3W for a maximum of 6 cycles; participants with non-squamous histologies may go on to receive optional treatment with pemetrexed 500 mg/m^2 IV on Day 1 Q3W.
a: Open Label Study
Outcome	Pembrolizumab N=637		SOC Treatment N=637		Effect Estimate	GRADE
Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.: Mok, TSK 2019. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.. ; 393 (10183); 1819-1830^*
Dichotomous Outcomes
OS - Time To Event	N=637	16.7 [13.9; 19.7]	N=637	12.1 [11.3; 13.3]	HR 0.81 [0.71; 0.93]; p=0.0018	⊕⊕⊕⊖
Programmed Cell Death Ligand 1 Tumor Proportion Score
≥20 %	N=413	17.7 [15.3; 22.1]	N=405	13.0 [11.6; 15.3]	HR 0.77 [0.64; 0.92]; p=0.0020
≥50 %	N=299	20.0 [15.4; 24.9]	N=300	12.2 [10.4; 14.2]	HR 0.69 [0.56; 0.85]; p=0.0003
1 - 49 %	N=338	13.4 [10.7; 18.2]	N=337	12.1 [11; 14]	HR 0.92 [0.77; 1.11]
PFS - Time To Event	N=637	5.4 [4.3; 6.2]	N=637	6.5 [6.3; 7]	HR 1.07 [0.94; 1.21]	⊕⊕⊖⊖^a
Programmed Cell Death Ligand 1 Tumor Proportion Score
≥20 %	N=413	6.2 [5.1; 7.8]	N=405	6.6 [6.2; 7.3]	HR 0.94 [0.8; 1.11]
≥50 %	N=299	7.1 [5.9; 9]	N=300	6.4 [6.1; 6.9]	HR 0.81 [0.67; 0.99]; p=0.0170
DOR - Time To Event	N=637	20.2	N=637	8.3		⊕⊕⊕⊖
Programmed Cell Death Ligand 1 Tumor Proportion Score
≥20 %	N=413	20.2	N=405	8.3
≥50 %	N=299	20.2	N=300	10.8
ORR - TuDD	N=637	174 (27.32%)	N=637	169 (26.53%)	RR 1.03 [0.859; 1.234]; p=0.7522	⊕⊕⊕⊖
Programmed Cell Death Ligand 1 Tumor Proportion Score
≥20 %	N=413	138 (33.414%)	N=405	117 (28.8889%)	RR 1.16 [0.943; 1.419]; p=0.1634
≥50 %	N=299	118 (39.4649%)	N=300	96 (32%)	RR 1.23 [0.993; 1.532]; p=0.0578
TAE (Any)	N=636	399 (62.74%)	N=615	553 (89.92%)	RR 0.7 [0.653; 0.745]; p=0.0000	⊕⊕⊖⊖^b
TAE (CTCAE ≥3)	N=636	113 (17.77%)	N=615	252 (40.98%)	RR 0.43 [0.358; 0.526]; p=0.0000	⊕⊕⊖⊖^b
TAE-D (Any)	N=636	13 (2.04%)	N=615	14 (2.28%)	RR 0.9 [0.426; 1.895]; p=0.7775	⊕⊕⊖⊖^b
TAE-D (CTCAE ≥3)	N=636	13 (2.04%)	N=615	14 (2.28%)	RR 0.9 [0.426; 1.895]; p=0.7775	⊕⊕⊖⊖^b
TAE-Disc (Any)	N=636	57 (8.96%)	N=615	58 (9.43%)	RR 0.95 [0.671; 1.346]; p=0.7743	⊕⊕⊖⊖^b
*Database cutoff: 25.02.2018
a: Missing individual analysis of combined endpoint componenets (progression); b: fehlende Verblindung bei subjektiver Endpunkterhebung
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; TAE: Treatment-related Adverse Events; TAE-D: Treatment-related Adverse Events Leading to Death; TAE-Disc: Treatment-related Adverse Events Leading to Treatment Discontinuation; TuDD: Time to Definitive Deterioration

Short Name	Design	Population	Intervention	Comparator	Outcomes
A Randomized Open-Label Phase III Trial of MK-3475 Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer(NCT02142738)
KEYNOTE-024 3475-024, 2014-000323-25, 142728, MK-3475-024	Randomized, Parallel Assignment, Phase 3 Open Label study	Patients with Stage 4 and ECOG 0-1 Non-Small Cell Lung Carcinoma	1. Pembrolizumab (N=154)¹	1. Paclitaxel+Carboplatin (N=151)² 2. Pemetrexed+Carboplatin (N=0)³ 3. Pemetrexed+Cisplatin (N=0)⁴ 4. Gemcitabine+Carboplatin (N=0)⁵ 5. Gemcitabine+Cisplatin (N=0)⁶	Primary: Progression Free Survival Secondary: Overall Survival Secondary: Objective Response Rate
Levels of Evidence
GRADE	⊕⊕⊕⊖^a	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
1: Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.; 2: Participants receive paclitaxel 200 mg/m^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.; 3: Participants receive pemetrexed 500 mg/m^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.; 4: Participants receive pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.; 5: Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.; 6: Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
a: Open Label Study
Outcome	Pembrolizumab N=154		Paclitaxel+Carboplatin N=151		Effect Estimate	GRADE
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.: Reck, M 2016. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.. ; 375 (19); 1823-1833^*
Dichotomous Outcomes
OS - Time To Event	N=154		N=151	N/A [9.4; ]	HR 0.6 [0.41; 0.89]; p=0.005	⊕⊕⊕⊖
PFS - Time To Event	N=154	10.3 [6.7; ]	N=151	6.0 [4.2; 6.2]	HR 0.5 [0.37; 0.68]; p<0.001	⊕⊕⊖⊖^a
Histologic type
Nonsquamous		N/A		N/A	HR 0.55 [0.39; 0.76]
Squamous		N/A		N/A	HR 0.35 [0.17; 0.71]
Platinum-based chemotherapy regimen
Did not include pemetrexed		N/A		N/A	HR 0.29 [0.17; 0.5]
Included pemetrexed		N/A		N/A	HR 0.63 [0.44; 0.91]
Region of enrollment
East Asia		N/A		N/A	HR 0.35 [0.14; 0.91]
Non-East Asia		N/A		N/A	HR 0.52 [0.38; 0.72]
Sex
Female		N/A		N/A	HR 0.75 [0.46; 1.21]
Male		N/A		N/A	HR 0.39 [0.26; 0.58]
Smoking status
Current		N/A		N/A	HR 0.68 [0.36; 1.31]
Former		N/A		N/A	HR 0.47 [0.33; 0.67]
Never		N/A		N/A	HR 0.9 [0.11; 7.59]
DOR - Time To Event	N=154	[1.9; 14.5]	N=151	6.3 [2.1; 12.6]	N/A	⊕⊕⊕⊖
ORR - TuDD	N=154	69 (44.81%)	N=151	42 (27.81%)	RR 1.61 [1.18; 2.199]; p=0.0027	⊕⊕⊕⊖
TTR - TTE	N=154	2.2 [1.4; 8.2]	N=151	2.2 [1.8; 12.2]	N/A	⊕⊕⊕⊖
TAE (Any)	N=154	113 (73.38%)	N=150	135 (90%)	RR 0.82 [0.731; 0.909]; p=0.0002	⊕⊕⊕⊖
TAE (CTCAE ≥3)	N=154	41 (26.62%)	N=150	80 (53.33%)	RR 0.5 [0.369; 0.675]; p=0.0000	⊕⊕⊕⊖
TAE-D (Any)	N=154	1 (0.65%)	N=150	3 (2%)	RR 0.32 [0.034; 3.087]; p=0.3275	⊕⊕⊕⊖
TAE-D (CTCAE ≥3)	N=154	1 (0.65%)	N=150	3 (2%)	RR 0.32 [0.034; 3.087]; p=0.3275	⊕⊕⊕⊖
TAE-Disc (Any)	N=154	11 (7.14%)	N=150	16 (10.67%)	RR 0.67 [0.321; 1.395]; p=0.2843	⊕⊕⊕⊖
*Database cutoff: 08.05.2016
a: Missing individual analysis of combined endpoint componenets (progression)
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; TAE: Treatment-related Adverse Events; TAE-D: Treatment-related Adverse Events Leading to Death; TAE-Disc: Treatment-related Adverse Events Leading to Treatment Discontinuation; TTE: Time To Event ; TTR: Time To Response; TuDD: Time to Definitive Deterioration

Short Name	Design	Population	Intervention	Comparator	Outcomes
A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non-Small Cell Lung Cancer(NCT02409342)
IMpower110 GO29431, 2014-003083-21	Randomized, Parallel Assignment, Phase 3 Open Label study	Treatment-naive with Stage 4 and ECOG 0-1 Non-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer	1. Atezolizumab (N=285)¹ 2. Indirekter Vergleich 1: Pembrolizumab (KEYNOTE-024) (N=154)² 3. Indirekter Vergleich 2: Pembrolizumab (KEYNOTE-042) (N=299)³ 4. Atezolizumab - TPS ≥ 50 % (PD-L1-Expression) (N=134)⁴		Primary: Overall Survival Secondary: Progression-free Survival Secondary: Objective Response Secondary: Duration of Response Secondary: Time to Deterioration (TTD) by Symptoms in Lung Cancer (SILC) Scale Symptom Score Secondary: Change From Baseline in SILC Scale Symptom Score
Levels of Evidence
GRADE	⊕⊕⊕⊖^a	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
1: Participants with squamous or non-squamous NSCLC will receive atezolizumab on Day 1 of each 21-day cycle until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity, or death (maximum up to approximately 58 months).; 2: Daten der gesamten Studienpopulation aus KEYNOTE-024 (NCT02142738); 3: Daten der relevanten Teilpopulation (mit PD-L1 ≥ 50 % auf den Tumorzellen gemäß 22C3-Assay) aus KEYNOTE-042 (NCT02220894); 4: Participants with squamous or non-squamous NSCLC and TPS ≥ 50 % (PD-L1-Expression) will receive atezolizumab on Day 1 of each 21-day cycle until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity, or death (maximum up to approximately 58 months).; 5: Participants with non-squamous NSCLC will receive chemotherapy with pemetrexed in combination with either cisplatin or carboplatin (per investigator discretion) on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by maintenance therapy with pemetrexed alone as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months). Participants with squamous NSCLC will receive chemotherapy with gemcitabine on Days 1 and 8 of each 21-day cycle in combination with either cisplatin or carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles as per local standard of care, followed by best supportive care as per local standard of care until disease progression, unacceptable toxicity, or death (maximum up to approximately 58 months).
a: Open Label Study
Outcome	Atezolizumab N=285		(Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine) N=287		Effect Estimate	GRADE
Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®): Teilpopulation Patienten mit PD-L1 hochexprimierendem (WT; TC3 oder IC3, SP142) NSCLC: Roche Pharma AG 2021. Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®). ^*
Dichotomous Outcomes
OS - Time To Event	N=107	20.2 [16.5; ]	N=98	13.1 [7.4; 16.5]	HR 0.59 [0.4; 0.89]; p=0.0106	⊕⊕⊕⊕
OS - Time To Event¹	N=107	20.2 [17.2; 27.9]	N=98	14.7 [7.4; 17.7]	HR 0.76 [0.54; 1.09]; p=0.1338	⊕⊕⊕⊕
PFS - Time To Event	N=107	8.1 [6.8; 11]	N=98	5.0 [4.2; 5.7]	HR 0.63 [0.45; 0.88]; p=0.0070	⊕⊕⊕⊖^a
DOR - Time To Event	N=107	[11.8; ]	N=98	6.7 [5.5; 17.3]	HR 0.36 [0.17; 0.8]; p=0.0096	⊕⊕⊕⊖^a
EORTC QLQ-C30 (Diarrhea) - TTC	N=107	N/A	N=98	N/A	HR 1.86 [0.98; 3.55]; p=0.0546	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Constipation) - TTC	N=107	N/A	N=98	N/A	HR 0.69 [0.42; 1.13]; p=0.1407	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Insomnia) - TTC	N=107	N/A	N=98	N/A	HR 1.27 [0.74; 2.18]; p=0.3801	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Dyspnea) - TTC	N=107	N/A	N=98	N/A	HR 0.97 [0.59; 1.57]; p=0.8904	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Pain) - TTC	N=107	N/A	N=98	N/A	HR 0.94 [0.6; 1.48]; p=0.7858	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Nausea) - TTC	N=107	N/A	N=98	N/A	HR 0.63 [0.37; 1.07]; p=0.0851	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Fatigue) - TTC	N=107	N/A	N=98	N/A	HR 1.01 [0.67; 1.52]; p=0.9630	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Lack of Appetite) - TTC	N=107	N/A	N=98	N/A	HR 0.66 [0.38; 1.14]; p=0.1334	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Haemoptysis) - TTC	N=107	N/A	N=98	N/A	HR 0.94 [0.32; 2.72]; p=0.9039	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Alopcia) - TTC	N=107	N/A	N=98	N/A	HR 0.34 [0.18; 0.62]; p=0.0003	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Peripheral neuropathy) - TTC	N=107	N/A	N=98	N/A	HR 1.05 [0.63; 1.74]; p=0.8477	⊕⊕⊖⊖^a,b
Histology
non-squamous epithelial	N=80	N/A	N=75	N/A	HR 0.77 [0.44; 1.35]; p=0.3689
squamous epithelial	N=27	N/A	N=23	N/A	HR 3.07 [0.85; 11.11]; p=0.0718
EORTC QLQ-LC13 (Dysphagia) - TTC	N=107	N/A	N=98	N/A	HR 1.06 [0.57; 1.95]; p=0.8566	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Dyspnea) - TTC	N=107	N/A	N=98	N/A	HR 0.95 [0.63; 1.43]; p=0.8145	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Coughing) - TTC	N=107	N/A	N=98	N/A	HR 0.94 [0.57; 1.54]; p=0.7999	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Sore mouth) - TTC	N=107	N/A	N=98	N/A	HR 0.78 [0.44; 1.4]; p=0.4034	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Pain in chest) - TTC	N=107	N/A	N=98	N/A	HR 0.91 [0.54; 1.53]; p=0.7158	⊕⊕⊖⊖^a,b
Histology
non-squamous epithelial	N=80	N/A	N=75	N/A	HR 0.64 [0.36; 1.14]; p=0.1259
squamous epithelial	N=27	N/A	N=23	N/A	HR 3.75 [0.8; 17.57]; p=0.0727
EORTC QLQ-LC13 (Pain in arm or shoulder) - TTC	N=107	N/A	N=98	N/A	HR 1.44 [0.83; 2.5]; p=0.1936	⊕⊕⊖⊖^a,b
EORTC QLQ-LC13 (Pain in other parts) - TTC	N=107	N/A	N=98	N/A	HR 0.68 [0.41; 1.11]; p=1.1229	⊕⊕⊖⊖^a,b
EQ-5D (VAS) - TTC	N=107	N/A	N=98	N/A	HR 1.01 [0.67; 1.53]; p=0.9612	⊕⊕⊖⊖^a,b
ORR - TuDD	N=107	41 (38.32%)	N=98	28 (28.57%)	RR 1.34 [0.904; 1.99]; p=0.1450	⊕⊕⊕⊖^a
EORTC QLQ-C30 (Emotional Function) - TTC	N=107	N/A	N=98	N/A	HR 0.84 [0.5; 1.39]; p=0.4914	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Physical Function) - TTC	N=107	N/A	N=98	N/A	HR 0.59 [0.37; 0.94]; p=0.0241	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Role Function) - TTC	N=107	N/A	N=98	N/A	HR 0.75 [0.49; 1.16]; p=0.1960	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Global Health Status) - TTC	N=107	N/A	N=98	N/A	HR 0.92 [0.59; 1.43]; p=0.7082	⊕⊕⊖⊖^a,b
EORTC QLQ-C30 (Social Function) - TTC	N=107	N/A	N=98	N/A	HR 1.07 [0.69; 1.66]; p=0.7552	⊕⊕⊖⊖^a,b
Histology
non-squamous epithelial	N=80	N/A	N=75	N/A	HR 0.79 [0.49; 1.28]; p=0.3343
squamous epithelial	N=27	N/A	N=23	N/A	HR 4.05 [1.33; 12.33]; p=0.0079
EORTC QLQ-C30 (Cognitive Function) - TTC	N=107	N/A	N=98	N/A	HR 0.74 [0.46; 1.18]; p=0.2028	⊕⊕⊖⊖^a,b
AE (Any)	N=107	98 (91.59%)	N=92	84 (91.3%)	RR 1 [0.921; 1.092]; p=0.9430	⊕⊕⊖⊖^c,a
AE (CTCAE ≥3)	N=107	40 (37.38%)	N=92	48 (52.17%)	RR 0.72 [0.524; 0.981]; p=0.0373	⊕⊕⊖⊖^c,a
AE (Any) - TTE	N=107	N/A	N=92	N/A	HR 0.7 [0.51; 0.95]; p=0.0217	⊕⊕⊖⊖^c,a
AE (CTCAE ≥3) - TTE	N=107	N/A	N=92	N/A	HR 0.51 [0.33; 0.79]; p=0.0021	⊕⊕⊖⊖^c,a
AE-Disc (Any)	N=107	7 (6.54%)	N=92	15 (16.3%)	RR 0.4 [0.171; 0.941]; p=0.0358	⊕⊕⊕⊖^a
AE-Disc (Any) - TTE	N=107	N/A	N=92	N/A	HR 0.29 [0.12; 0.73]; p=0.0053	⊕⊕⊖⊖^a
SAE (Any)	N=107	34 (31.78%)	N=92	20 (21.74%)	RR 1.46 [0.907; 2.355]; p=0.1187	⊕⊕⊖⊖^c,a
SAE (Any) - TTE	N=107	N/A	N=92	N/A	HR 1.36 [0.78; 2.37]; p=0.2792	⊕⊕⊖⊖^c,a
Outcome	Atezolizumab N=285		Indirekter Vergleich 1: Pembrolizumab (KEYNOTE-024) N=154		Effect Estimate	GRADE
Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®): Indirekter Vergleich aus RCTs IMpower110 vs. KEYNOTE-024: Roche Pharma AG 2021. Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®). ^**
Dichotomous Outcomes
OS - Time To Event	N=134	N/A	N=154	N/A	HR 0.95 [0.56; 1.63]	⊕⊕⊕⊕
AE (Any) - TTE	N=134	N/A	N=154	N/A	HR 0.76 [0.53; 1.1]	⊕⊕⊖⊖^c
AE (CTCAE ≥3) - TTE	N=134	N/A	N=154	N/A	HR 0.76 [0.46; 1.25]	⊕⊕⊖⊖^c
AE-Disc (Any) - TTE	N=134	N/A	N=154	N/A	HR 0.2 [0.06; 0.63]	⊕⊕⊖⊖^c
SAE (Any) - TTE	N=134	N/A	N=154	N/A	HR 0.87 [0.48; 1.57]	⊕⊕⊖⊖^c
Outcome	Atezolizumab N=285		Indirekter Vergleich 2: Pembrolizumab (KEYNOTE-042) N=299		Effect Estimate	GRADE
Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®): Indirekter Vergleich aus RCTs IMpower110 vs. KEYNOTE-042: Roche Pharma AG 2021. Modul 4 der Nutzenbewertung von Atezolizumab (Tecentriq®). ^***
Dichotomous Outcomes
OS - Time To Event	N=134	N/A	N=299	N/A	HR 0.83 [0.54; 1.27]	⊕⊕⊕⊕
Outcome	Atezolizumab N=285				Effect Estimate	GRADE
Nutzenbewertung IQWiG der Nutzenbewertung von Atezolizumab (Tecentriq®): Indirekter Vergleich Atezolizumab vs. Pembrolizumab: IQWiG 2021. Nutzenbewertung IQWiG der Nutzenbewertung von Atezolizumab (Tecentriq®). ^****
Dichotomous Outcomes
OS - Time To Event	N=134	N/A	N=363	N/A	HR 0.85 [0.56; 1.29]; p=0.449	⊕⊕⊕⊕
Outcome	Atezolizumab N=285				Effect Estimate	GRADE
Addendum zur Nutzenbewertung des IQWiG zur Nutzenbewertung von Atezolizumab (Tecentriq®): Atezolizumab vs. Pembrolizumab, Patientinnen und Patienten mit hochexprimierendem PD-L1: IQWiG 2021. Addendum zur Nutzenbewertung des IQWiG zur Nutzenbewertung von Atezolizumab (Tecentriq®). ^*****
Dichotomous Outcomes
AE (CTCAE ≥3) - TTE	N=134		N/A		HR 0.76 [0.46; 1.25]; p=0.282	⊕⊕⊕⊖^c
AE-Disc (Any) - TTE	N=134		N/A		HR 0.2 [0.06; 0.63]; p=0.007	⊕⊕⊖⊖^d
SAE (Any) - TTE	N=134		N/A		HR 0.87 [0.48; 1.57]; p=0.645	⊕⊕⊕⊖^c
Database cutoff: 03.09.2018 Database cutoff: not reported Database cutoff: not reported Database cutoff: not reported ***Database cutoff: not reported
1: explorativer Datenschnitt vom 04.02.2020
a: Fehlende Verblindung; b: im Studienverlauf sinkender Rücklauf von Fragebogen; c: unvollständige Beobachtungen aus potenziell informativen Gründen; d: fehlende Verblindung bei subjektiver Entscheidung zum Therapieabbruch
AE: Adverse Events; AE-Disc: Adverse Events Leading to Treatment Discontinuation; Alopcia: Alopcia; Any: Any Grade; Cognitive Function: Cognitive Function; Constipation: Constipation; Coughing: Coughing; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; Diarrhea: Diarrhea; DOR: Duration Of Response; Dysphagia: Dysphagia; Dyspnea: Dyspnea; Emotional Function: Emotional Function; EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; EORTC QLQ-LC13: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Module; EQ-5D: European Quality of Life 5 Dimensions; Fatigue: Fatigue; Global Health Status: Global Health Status; Haemoptysis: Haemoptysis; Insomnia: Insomnia; Lack of Appetite: Lack of Appetite; Nausea: Nausea; ORR: Objective Response Rate; OS: Overall Survival; Pain: Pain; Pain in arm or shoulder: Pain in arm or shoulder; Pain in chest: Pain in chest; Pain in other parts: Pain in other parts; Peripheral neuropathy: Peripheral neuropathy; PFS: Progression-Free Survival; Physical Function: Physical Function; Role Function: Role Function; SAE: Serious Adverse Events; Social Function: Social Function; Sore mouth: Sore mouth; TTC: Time To Change ; TTE: Time To Event ; TuDD: Time to Definitive Deterioration ; VAS: Visual Analogue Scale