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
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 35(2024), 1 vom: 18. Jan., Seite 77-90 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Passaro, A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.01.2024 Date Revised 27.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2023.10.117 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib |b primary results from the phase III MARIPOSA-2 study |
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| 500 | |a Date Revised 27.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EGFR-mutated | |
| 650 | 4 | |a NSCLC | |
| 650 | 4 | |a amivantamab | |
| 650 | 4 | |a lazertinib | |
| 650 | 4 | |a post-osimertinib | |
| 650 | 7 | |a Acrylamides |2 NLM | |
| 650 | 7 | |a amivantamab-vmjw |2 NLM | |
| 650 | 7 | |a Aniline Compounds |2 NLM | |
| 650 | 7 | |a Antibodies, Bispecific |2 NLM | |
| 650 | 7 | |a Carboplatin |2 NLM | |
| 650 | 7 | |a BG3F62OND5 |2 NLM | |
| 650 | 7 | |a EGFR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a ErbB Receptors |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a lazertinib |2 NLM | |
| 650 | 7 | |a 4A2Y23XK11 |2 NLM | |
| 650 | 7 | |a Morpholines |2 NLM | |
| 650 | 7 | |a osimertinib |2 NLM | |
| 650 | 7 | |a 3C06JJ0Z2O |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 700 | 1 | |a Wang, J |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, S-H |e verfasserin |4 aut | |
| 700 | 1 | |a Melosky, B |e verfasserin |4 aut | |
| 700 | 1 | |a Shih, J-Y |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, J |e verfasserin |4 aut | |
| 700 | 1 | |a Azuma, K |e verfasserin |4 aut | |
| 700 | 1 | |a Juan-Vidal, O |e verfasserin |4 aut | |
| 700 | 1 | |a Cobo, M |e verfasserin |4 aut | |
| 700 | 1 | |a Felip, E |e verfasserin |4 aut | |
| 700 | 1 | |a Girard, N |e verfasserin |4 aut | |
| 700 | 1 | |a Cortot, A B |e verfasserin |4 aut | |
| 700 | 1 | |a Califano, R |e verfasserin |4 aut | |
| 700 | 1 | |a Cappuzzo, F |e verfasserin |4 aut | |
| 700 | 1 | |a Owen, S |e verfasserin |4 aut | |
| 700 | 1 | |a Popat, S |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, J-L |e verfasserin |4 aut | |
| 700 | 1 | |a Salinas, J |e verfasserin |4 aut | |
| 700 | 1 | |a Tomasini, P |e verfasserin |4 aut | |
| 700 | 1 | |a Gentzler, R D |e verfasserin |4 aut | |
| 700 | 1 | |a William, W N |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Reckamp, K L |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, T |e verfasserin |4 aut | |
| 700 | 1 | |a Ganguly, S |e verfasserin |4 aut | |
| 700 | 1 | |a Kowalski, D M |e verfasserin |4 aut | |
| 700 | 1 | |a Bearz, A |e verfasserin |4 aut | |
| 700 | 1 | |a MacKean, M |e verfasserin |4 aut | |
| 700 | 1 | |a Barala, P |e verfasserin |4 aut | |
| 700 | 1 | |a Bourla, A B |e verfasserin |4 aut | |
| 700 | 1 | |a Girvin, A |e verfasserin |4 aut | |
| 700 | 1 | |a Greger, J |e verfasserin |4 aut | |
| 700 | 1 | |a Millington, D |e verfasserin |4 aut | |
| 700 | 1 | |a Withelder, M |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, J |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, T |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, S |e verfasserin |4 aut | |
| 700 | 1 | |a Diorio, B |e verfasserin |4 aut | |
| 700 | 1 | |a Knoblauch, R E |e verfasserin |4 aut | |
| 700 | 1 | |a Bauml, J M |e verfasserin |4 aut | |
| 700 | 1 | |a Campelo, R G |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, B C |e verfasserin |4 aut | |
| 700 | 0 | |a MARIPOSA-2 Investigators |e verfasserin |4 aut | |
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