PMID- 36652175
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230326
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 40
IP  - 3
DP  - 2023 Mar
TI  - An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical 
      Practice in Europe and the United States for Patients with Advanced Non-Small 
      Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 
      Insertion Mutations.
PG  - 1187-1203
LID - 10.1007/s12325-022-02408-7 [doi]
AB  - INTRODUCTION: Patients with advanced, epidermal growth factor receptor 
      (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion 
      mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of 
      specific treatment guidelines and unmet need for targeted therapies. Amivantamab, 
      an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in 
      patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based 
      therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, 
      individual patient data (IPD)-based adjusted analyses versus similar patients in 
      real-world clinical practice (RWCP) were conducted to generate comparative 
      evidence. METHODS: RWCP cohorts were derived from seven European and US 
      real-world sources, comprising patients fulfilling CHRYSALIS Cohort 
      D+ eligibility criteria. Amivantamab was compared with a basket of RWCP 
      treatments. Differences in prognostic characteristics were adjusted for using 
      inverse probability weighting (IPW; average treatment effect among the treated 
      [ATT]). Balance between cohorts was assessed using standardized mean differences 
      (SMDs). Overall response rate (ORR; investigator- [INV] and independent review 
      committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; 
      INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and 
      time-to-event endpoints were analyzed using weighted logistic regression and 
      proportional hazards regression, respectively. RESULTS: Pre-adjustment, baseline 
      characteristics were comparable between cohorts. IPW ATT-adjustment improved 
      comparability, giving closely matched characteristics. ORR (INV) was 36.8% for 
      amivantamab versus 17.0% for the adjusted EU + US cohort (response rate ratio 
      [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52 months (hazard 
      ratio [HR]: 0.47; p < 0.0001), 6.93 versus 4.17 months (HR: 0.55; p < 0.0001) and 
      12.42 versus 5.36 months (HR: 0.44; p < 0.0001) for amivantamab versus the 
      adjusted EU + US cohort, respectively. Results were consistent versus EU- and 
      US-only cohorts, and when using IRC assessment. CONCLUSION: Adjusted comparisons 
      demonstrated significantly improved outcomes for amivantamab versus RWCP, 
      highlighting the value of amivantamab in addressing unmet need in patients with 
      advanced EGFR Exon20ins NSCLC following platinum-based therapy. TRIAL 
      REGISTRATION: CHRYSALIS: NCT02609776.
CI  - (c) 2023. The Author(s).
FAU - Chouaid, Christos
AU  - Chouaid C
AUID- ORCID: 0000-0002-4290-5524
AD  - Service de Pneumologie, Pneumology, Intercommunal Hospital, 40 avenue de Verdun, 
      94010, Creteil, France. christos.chouaid@chicreteil.fr.
FAU - Bosquet, Lise
AU  - Bosquet L
AUID- ORCID: 0000-0001-5100-9425
AD  - Health Data and Partnerships Department, Unicancer, Paris, France.
FAU - Girard, Nicolas
AU  - Girard N
AUID- ORCID: 0000-0001-9909-2299
AD  - Institut Curie, Paris, France.
FAU - Kron, Anna
AU  - Kron A
AUID- ORCID: 0000-0002-3047-6486
AD  - Lung Cancer Group Cologne, Department I for Internal Medicine and Center for 
      Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany.
AD  - Network Genomic Medicine, Cologne, Germany.
AD  - Department I of Internal Medicine, Faculty of Medicine and University Hospital 
      Cologne, University of Cologne, Cologne, Germany.
FAU - Scheffler, Matthias
AU  - Scheffler M
AUID- ORCID: 0000-0002-9031-1368
AD  - Lung Cancer Group Cologne, Department I for Internal Medicine and Center for 
      Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany.
AD  - Network Genomic Medicine, Cologne, Germany.
AD  - Department I of Internal Medicine, Faculty of Medicine and University Hospital 
      Cologne, University of Cologne, Cologne, Germany.
FAU - Griesinger, Frank
AU  - Griesinger F
AUID- ORCID: 0000-0002-6822-5498
AD  - Department of Hematology and Oncology, University Department Internal 
      Medicine-Oncology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, 
      Germany.
FAU - Sebastian, Martin
AU  - Sebastian M
AUID- ORCID: 0000-0002-0404-7741
AD  - Department of Medicine, Hematology and Oncology, University of Frankfurt, 
      Frankfurt, Germany.
FAU - Trigo, Jose
AU  - Trigo J
AUID- ORCID: 0000-0002-4489-2683
AD  - Hospital Universitario Virgen de la Victoria y Regional, IBIMA, Malaga, Spain.
FAU - Viteri, Santiago
AU  - Viteri S
AUID- ORCID: 0000-0001-8877-4649
AD  - UOMI Cancer Center, Clinica Mi Tres Torres, Barcelona, Spain.
AD  - Instituto Oncologico Dr Rosell, Hospital Universitari Dexeus, Grupo QuironSalud, 
      Barcelona, Spain.
FAU - Knott, Craig
AU  - Knott C
AUID- ORCID: 0000-0002-8593-6216
AD  - Health Data Insight CIC, Cambridge, UK.
AD  - National Disease Registration Service, NHS Digital, Leeds, UK.
FAU - Rodrigues, Bernardo
AU  - Rodrigues B
AD  - Janssen Cilag, Porto Salvo, Portugal.
FAU - Rahhali, Nora
AU  - Rahhali N
AUID- ORCID: 0000-0002-7989-6035
AD  - Janssen Cilag, Ile-de-France, France.
FAU - Cabrieto, Jedelyn
AU  - Cabrieto J
AUID- ORCID: 0000-0001-6413-2000
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Diels, Joris
AU  - Diels J
AUID- ORCID: 0000-0002-9456-9120
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Perualila, Nolen J
AU  - Perualila NJ
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Schioppa, Claudio A
AU  - Schioppa CA
AUID- ORCID: 0000-0002-4148-4676
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Sermon, Jan
AU  - Sermon J
AD  - Janssen Pharmaceutica NV, Beerse, Belgium.
FAU - Toueg, Raphael
AU  - Toueg R
AD  - Janssen Cilag, Ile-de-France, France.
FAU - Erdmann, Nicole
AU  - Erdmann N
AD  - Janssen-Cilag GmbH, Neuss, Germany.
FAU - Mielke, Janka
AU  - Mielke J
AD  - Janssen-Cilag GmbH, Neuss, Germany.
FAU - Nematian-Samani, Mehregan
AU  - Nematian-Samani M
AD  - Janssen-Cilag GmbH, Neuss, Germany.
FAU - Martin-Fernandez, Cristina
AU  - Martin-Fernandez C
AD  - Janssen-Cilag Ltd, High Wycombe, UK.
FAU - Pfaira, Innocent
AU  - Pfaira I
AD  - Janssen-Cilag Ltd, High Wycombe, UK.
FAU - Li, Tracy
AU  - Li T
AD  - Janssen R&D, Raritan, NJ, USA.
FAU - Mahadevia, Parthiv
AU  - Mahadevia P
AD  - Janssen R&D, Raritan, NJ, USA.
FAU - Wolf, Jurgen
AU  - Wolf J
AUID- ORCID: 0000-0002-3869-4736
AD  - Lung Cancer Group Cologne, Department I for Internal Medicine and Center for 
      Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany.
AD  - Network Genomic Medicine, Cologne, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02609776
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230118
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (amivantamab-vmjw)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 0 (Protein Kinase Inhibitors)
MH  - Humans
MH  - United States
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - *Antineoplastic Agents/therapeutic use
MH  - Mutagenesis, Insertional
MH  - ErbB Receptors/genetics/therapeutic use
MH  - Mutation
MH  - Protein Kinase Inhibitors/therapeutic use
PMC - PMC9988783
OTO - NOTNLM
OT  - Adjusted comparison
OT  - Amivantamab
OT  - Exon 20 insertion mutations
OT  - Non-small cell lung cancer
OT  - Real-world clinical practice
EDAT- 2023/01/19 06:00
MHDA- 2023/03/09 06:00
PMCR- 2023/01/18
CRDT- 2023/01/18 11:28
PHST- 2022/10/05 00:00 [received]
PHST- 2022/12/12 00:00 [accepted]
PHST- 2023/01/19 06:00 [pubmed]
PHST- 2023/03/09 06:00 [medline]
PHST- 2023/01/18 11:28 [entrez]
PHST- 2023/01/18 00:00 [pmc-release]
AID - 10.1007/s12325-022-02408-7 [pii]
AID - 2408 [pii]
AID - 10.1007/s12325-022-02408-7 [doi]
PST - ppublish
SO  - Adv Ther. 2023 Mar;40(3):1187-1203. doi: 10.1007/s12325-022-02408-7. Epub 2023 
      Jan 18.