Portal de investigación
Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Passaro A
- Wang Y
- Lee SH
- Melosky B
- Shih JY
- Wang J
- Azuma K
- Cobo M
- Felip E
- Girard N
- Cortot AB
- Califano R
- Cappuzzo F
- Owen S
- Popat S
- Tan JL
- Salinas J
- Tomasini P
- Gentzler RD
- William WN Jr
- Reckamp KL
- Takahashi T
- Ganguly S
- Kowalski DM
- Bearz A
- MacKean M
- Barala P
- Bourla AB
- Girvin A
- Greger J
- Millington D
- Withelder M
- Xie J
- Sun T
- Shah S
- Diorio B
- Knoblauch RE
- Bauml JM
- Campelo RG
- Cho BC
- MARIPOSA-2 Investigators
Grupos
Abstract
BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 0923-7534, 1569-8041
- Tipo:
- Article
- Páginas:
- 77-90
- PubMed:
- 37879444
- Factor de Impacto:
- 8,590 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ANNALS OF ONCOLOGY ELSEVIER
Citas Recibidas en Web of Science: 416
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Filiaciones
Keywords
- EGFR-mutated; NSCLC; amivantamab; lazertinib; post-osimertinib