Tremelimumab + Durvalumab plus Chemotherapie NSCLC Stadium IV Erstlinie, Poseidon

Lungenkarzinom · Version 5.1

Tremelimumab (nicht-kleinzelliges Lungenkarzinom, EGFR/ALK-negativ, Erstlinie, Kombination mit Durvalumab und platinbasierter Chemotherapie)
Wirkstoff Tremelimumab Handelsname Tremelimumab AstraZeneca
Pharmazeutischer Unternehmer AstraZeneca GmbH Beschlussdatum 01.09.2023
Anwendungsgebiet Nicht-kleinzelliges Lungenkarzinom
Population/ZVT Titel Mortalität Morbidiät QoL Sicherheit Zusatznutzen
A Tremelimumab + Durvalumab bei erwachsenen Patientinnen und Patienten mit metastasiertem NSCLC mit einer PD-L1-Expression ≥ 50 % ↔

geringerer Nutzen / Zusatznutzen nicht

 Ø

keine geeigneten Daten

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keine geeigneten Daten

 Ø

keine geeigneten Daten

 ist nicht belegt
ZVT Platinbasierte Chemotherapie
B Tremelimumab + Durvalumab bei erwachsenen Patientinnen und Patienten mit metastasiertem NSCLC mit einer PD-L1-Expression < 50 % Ø

keine geeigneten Daten

 Ø

keine geeigneten Daten

 Ø

keine geeigneten Daten

 Ø

keine geeigneten Daten

 ist nicht belegt
ZVT platinbasierte Chemotherapie
↑↑/↓↓: 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

A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON) (NCT03164616)
Short Name Design Population Intervention Comparator Outcomes
POSEIDON
D419MC00004, 2017-000920-81		 Randomized, Parallel Assignment, Phase 3 Open Label study Treatment-naive with Stage 4 and ECOG 0-1 Non Small Cell Lung Cancer NSCLC 1. Tremelimumba + Durvalumab + Chemotherapy (N=338)1
2. Durvalumab + Chemotherapy (N=338)2		 Chemotherapy (N=337)3
  1. Primary: Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
  2. Primary: Overall Survival (OS); D + SoC Compared With SoC Alone
  3. Secondary: PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
  4. Secondary: OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
  5. Secondary: Objective Response Rate (ORR)
  6. Secondary: Best Objective Response (BoR)
  7. Secondary: Duration of Response (DoR)
  8. Secondary: Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)
  9. Secondary: Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
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: durvalumab + tremelimumab combination therapy + SoC chemotherapy; 2: durvalumab monotherapy + SoC chemotherapy; 3: SoC chemotherapy alone
a: Open Label Study

Outcome Tremelimumba + Durvalumab + Chemotherapy N=338 Chemotherapy N=337 Effect Estimate GRADE
Durvalumab With Tremelimumab in Combination With Chemotherapy: Johnson, ML 2023. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.. ; 41 (6); 1213-1227*
Dichotomous Outcomes
OS - Time To Event N=338 14.0 [11.7; 16.1] N=337 11.7 [10.5; 13.1] HR 0.77 [0.65; 0.92]; p=0.0030 ⊕⊕⊕⊖
AJCC disease stage
IV A N=171 N=166 HR 0.72 [0.56; 0.91]
IV B N=165 N=170 HR 0.84 [0.66; 1.06]
ECOG
0 N=110 N=119 HR 0.8 [0.59; 1.09]
1 N=228 N=218 HR 0.72 [0.59; 0.89]
Histology
Nonsquamous N=214 17.2 [14.9; 21.8] N=214 13.1 [10.6; 15.1] HR 0.7 [0.56; 0.87]
Squamous N=124 10.4 [8.4; 12.7] N=122 10.5 [8; 11.7] HR 0.88 [0.68; 1.16]
Planned chemotherapy
Gemcitabine N=111 N=111 HR 0.9 [0.68; 1.19]
Nab-paclitaxel N=23 N=19 HR 0.55 [0.27; 1.11]
Pemetrexed N=204 [; ] N=207 HR 0.72 [0.57; 0.9]
Race
Asian N=99 N=128 HR 0.97 [0.71; 1.3]
Non-Asian N=239 N=209 HR 0.65 [0.53; 0.8]
Sex
Female N=69 [; ] N=89 HR 0.96 [0.66; 1.38]
Male N=269 [; ] N=248 HR 0.7 [0.58; 0.85]
Smoking history
Current N=84 N=66 HR 0.54 [0.37; 0.79]
Former N=195 N=191 HR 0.75 [0.6; 0.94]
Never N=59 [; ] N=79 HR 1.15 [0.79; 1.67]
PFS - Time To Event N=338 6.2 [5; 6.5] N=337 4.8 [4.6; 5.8] HR 0.72 [0.6; 0.86]; p=0.0003 ⊕⊕⊖⊖a
Histology
Nonquamous N=209 6.8 [6.1; 8.5] N=214 5.5 [4.8; 6.4] HR 0.66 [0.52; 0.84]
Squamous N=128 4.6 [3.9; 5.1] N=122 4.6 [4.2; 4.8] HR 0.77 [0.58; 1.01]
DOR - Time To Event N=335 9.5 [7.2; ] N=332 5.1 [4.4; 6] ⊕⊖⊖⊖b
ORR - TuDD N=335 130 (38.81%) N=332 81 (24.4%) RR 1.59 [1.261; 2.006]; p=0.0001 ⊕⊕⊕⊖
TAE (Any) N=330 306 (92.73%) N=333 298 (89.49%) RR 1.04 [0.988; 1.087]; p=0.1435 ⊕⊕⊕⊖
TAE (CTCAE ≥3) N=330 171 (51.82%) N=333 148 (44.44%) RR 1.17 [0.995; 1.367]; p=0.0583 ⊕⊕⊕⊖
TAE-Disc (Any) N=330 51 (15.45%) N=333 33 (9.91%) RR 1.56 [1.034; 2.351]; p=0.0339 ⊕⊕⊕⊖
TAE-Disc (CTCAE ≥3) N=330 31 (9.39%) N=333 14 (4.2%) RR 2.23 [1.211; 4.123]; p=0.0101 ⊕⊕⊕⊖
TirAE-D (Any) N=330 11 (3.33%) N=333 8 (2.4%) RR 1.39 [0.565; 3.406]; p=0.4747 ⊕⊕⊕⊖
TSAE (Any) N=330 91 (27.58%) N=333 59 (17.72%) RR 1.56 [1.164; 2.08]; p=0.0028 ⊕⊕⊕⊖
TSAE (CTCAE ≥3) N=330 70 (21.21%) N=333 44 (13.21%) RR 1.61 [1.137; 2.267]; p=0.0072 ⊕⊕⊕⊖
Outcome Durvalumab + Chemotherapy N=338 Chemotherapy N=337 Effect Estimate GRADE
Durvalumab Without Tremelimumab in Combination With Chemotherapy: Johnson, ML 2023. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.. ; 41 (6); 1213-1227**
Dichotomous Outcomes
OS - Time To Event N=338 13.3 [11.4; 14.7] N=337 11.7 [10.5; 13.1] HR 0.86 [0.72; 1.02]; p=0.0758 ⊕⊕⊕⊖
AJCC disease stage
IV A N=170 N=166 HR 0.71 [0.55; 0.91]
IV B N=167 N=170 HR 1 [0.79; 1.26]
Race
Asian N=123 N=128 HR 0.92 [0.69; 1.22]
Non-Asian N=215 N=209 HR 0.78 [0.63; 0.96]
Sex
Female N=85 N=89 HR 0.91 [0.64; 1.3]
Male N=253 N=248 HR 0.81 [0.67; 0.98]
Tumor PD-L1 expression
TC <50% N=243 N=240 HR 0.94 [0.77; 1.14]
TC >=1% N=224 [; ] N=207 HR 0.79 [0.64; 0.98]
TC >=50% N=94 N=97 HR 0.63 [0.45; 0.88]
TC<1% N=113 [; ] N=130 HR 0.99 [0.76; 1.3]
PFS - Time To Event N=338 5.5 [4.7; 6.5] N=337 4.8 [4.6; 5.8] HR 0.74 [0.62; 0.89]; p=0.0009 ⊕⊕⊖⊖a
Histology
Nonsquamous N=209 6.4 [4.7; 7.4] N=214 5.5 [4.8; 6.4] HR 0.77 [0.61; 0.96]
Squamous N=128 4.7 [4.6; 6.3] N=122 4.6 [4.2; 4.8] HR 0.68 [0.52; 0.9]
DOR - Time To Event N=330 7.0 [5.7; 9.9] N=332 5.1 [4.4; 6] ⊕⊖⊖⊖b
ORR - TuDD N=330 137 (41.52%) N=332 81 (24.4%) RR 1.7 [1.354; 2.139]; p=0.0000 ⊕⊕⊕⊖
TAE (Any) N=334 296 (88.62%) N=333 298 (89.49%) RR 0.99 [0.939; 1.044]; p=0.7200 ⊕⊕⊕⊖
TAE (CTCAE ≥3) N=334 149 (44.61%) N=333 148 (44.44%) RR 1 [0.847; 1.189]; p=0.9655 ⊕⊕⊕⊖
TAE-D (Any) N=334 7 (2.1%) N=333 8 (2.4%) RR 0.87 [0.32; 2.378]; p=0.7896 ⊕⊕⊕⊖
TAE-Disc (Any) N=334 47 (14.07%) N=333 33 (9.91%) RR 1.42 [0.934; 2.158]; p=0.1005 ⊕⊕⊕⊖
TAE-Disc (CTCAE ≥3) N=334 24 (7.19%) N=333 14 (4.2%) RR 1.71 [0.9; 3.246]; p=0.1015 ⊕⊕⊕⊖
TSAE (Any) N=334 48 (14.37%) N=333 59 (17.72%) RR 0.81 [0.572; 1.15]; p=0.2403 ⊕⊕⊕⊖
TSAE (CTCAE ≥3) N=334 48 (14.37%) N=333 44 (13.21%) RR 1.09 [0.744; 1.59]; p=0.6647 ⊕⊕⊕⊖
Outcome Tremelimumba + Durvalumab + Chemotherapy N=338 Chemotherapy N=337 Effect Estimate GRADE
Tremelimumab + Durvalumab + platinbasierte Chemotherapie vs. Pembrolizumab - Nutzenbewertung gemäß § 35a SGB V: IQWiG 2023. Tremelimumab und Durvalumab - Nutzenbewertung gemäß § 35a SGB V. ***
Dichotomous Outcomes
OS - Time To Event1 N=554 0.65 [0.47; 0.89] N=548 0.67 [0.56; 0.8] HR 0.97 [0.67; 1.41]; p=0.873 ⊕⊕⊕⊖
Outcome Tremelimumba + Durvalumab + Chemotherapy N=338 Chemotherapy N=337 Effect Estimate GRADE
Study of Durvalumab + Tremelimumab With Chemotherapy vs. Chemotherapy Alone for Patients With Lung Cancer (POSEIDON): ClinicalTrials.gov 2022. Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). ****
Dichotomous Outcomes
EORTC QLQ-C30 (Global Health Status) - TTD N=319 8.3 [6.4; 10.2] N=318 5.6 [4.4; 7.5] ⊕⊖⊖⊖b
AE (Any) N=330 309 (93.64%) N=333 301 (90.39%) RR 1.04 [0.99; 1.084]; p=0.1237 ⊕⊕⊕⊖
SAE (Any) N=330 146 (44.24%) N=337 117 (34.72%) RR 1.27 [1.054; 1.541]; p=0.0124 ⊕⊕⊕⊖
Outcome Durvalumab + Chemotherapy N=338 Chemotherapy N=337 Effect Estimate GRADE
Study of Durvalumab + Tremelimumab With Chemotherapy vs. Chemotherapy Alone for Patients With Lung Cancer (POSEIDON): ClinicalTrials.gov 2022. Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). *****
Dichotomous Outcomes
EORTC QLQ-C30 (Global Health Status) - TTD N=321 7.8 [6.5; 9.5] N=318 5.6 [4.4; 7.5] ⊕⊕⊖⊖b
AE (Any) N=334 302 (90.42%) N=333 301 (90.39%) RR 1 [0.952; 1.051]; p=0.9899 ⊕⊕⊕⊖
SAE (Any) N=334 134 (40.12%) N=333 117 (35.14%) RR 1.14 [0.939; 1.389]; p=0.1849 ⊕⊕⊕⊖
*Database cutoff: 11.03.2021
**Database cutoff: 11.03.2021
***Database cutoff: 09.03.2021
****Database cutoff: 10.03.2021
*****Database cutoff: 10.03.3021
1: indirekter Vergleich nach Bucher
a: Fehlende Einzelauswertung der Komponenten des zusammengesetzten Endpunktes (Progression); b: Keine Effektschätzer berichtet
AE: Adverse Events; Any: Any Grade; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; DOR: Duration Of Response; EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; Global Health Status: Global Health Status; MCID: Minimal Clinically Important Difference; ORR: Objective Response Rate; OS: Overall Survival; PFS: Progression-Free Survival; 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; TirAE-D: Treatment-related immun-related Advers Events Leading to Death; TSAE: Treatment-related Serious Adverse Events; TTD: Time to Deterioration ; TuDD: Time to Definitive Deterioration