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.
Date
2023-10-23ICR Author
Author
Passaro, A
Wang, J
Wang, Y
Lee, S-H
Melosky, B
Shih, J-Y
Wang, J
Azuma, K
Juan-Vidal, O
Cobo, M
Felip, E
Girard, N
Cortot, AB
Califano, R
Cappuzzo, F
Owen, S
Popat, S
Tan, J-L
Salinas, J
Tomasini, P
Gentzler, RD
William, WN
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
EGFR-mutated
NSCLC
amivantamab
lazertinib
post-osimertinib
Language
eng
Date accepted
2023-10-12
License start date
2023-10-23
Citation
Annals of Oncology, 2023, pp. S0923-7534(23)04281-3 -
Publisher
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