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Combination treatment with amivantamab and lazertinib is more effective than osimertinib monotherapy for patients with treatment-naïve, EGFR-mutant, advanced non-small cell lung cancer (NSCLC), according to data from the MARIPOSA trial.
Amivantamab plus lazertinib improved progression-free survival (PFS) and prolonged the duration of response in this phase 3 trial. There was a trend toward improved overall survival (OS) with the combination as well.
“Based on the MARIPOSA study, amivantamab plus lazertinib represents a new standard of care in patients with first-line, EGFR-mutant advanced NSCLC,” said study investigator Byoung Chul Cho, MD, PhD, of Yonsei Cancer Center at Yonsei University in Seoul, Republic of Korea.
Dr Cho presented results from MARIPOSA (ClinicalTrials.gov Identifier: NCT04487080) at the ESMO Congress 2023.
The trial included 1074 patients with treatment-naïve, EGFR-mutant, locally advanced or metastatic NSCLC. They were randomly assigned to receive amivantamab plus lazertinib (n=429), osimertinib alone (n=429), or lazertinib alone (n=216).
Amivantamab was given at 1050 mg (1400 mg if ≥80 kg) weekly for the first 4 weeks, then every 2 weeks. Lazertinib was given at 240 mg daily. Osimertinib was given at 80 mg daily.
The primary endpoint was PFS for amivantamab plus lazertinib compared to osimertinib, as determined by blinded independent central review.
At a median follow-up of 22.0 months, the median PFS was 23.7 months with amivantamab plus lazertinib and 16.6 months with osimertinib (hazard ratio [HR], 0.70; 95% CI, 0.58-0.85; P <.001).
The 12-month PFS rate was 73% with amivantamab plus lazertinib and 65% with osimertinib. The 24-month PFS rate was 48% and 34%, respectively. PFS favored amivantamab plus lazertinib across subgroups.
Lazertinib alone also demonstrated meaningful clinical activity, Dr Cho said. The median PFS was 18.5 months with lazertinib alone.
The median extracranial PFS was 27.5 months with amivantamab plus lazertinib and 18.5 months with osimertinib (HR, 0.68; 95% CI, 0.56-0.83; P <.001). The 12-month extracranial PFS rate was 77% with amivantamab plus lazertinib and 67% with osimertinib. The 24-month extracranial PFS rate was 53% and 38%, respectively.
PFS after first subsequent therapy (PFS2) was also longer in the amivantamab-lazertinib arm. The 24-month PFS2 rate was 72% in the combination arm and 64% in the osimertinib arm (HR, 0.75; 95% CI, 0.58-0.98; P =.03).
The objective response rate was 86% with amivantamab plus lazertinib and 85% with osimertinib. The median duration of response was 25.8 months and 16.8 months, respectively.
Early OS data showed a trend toward improved OS for amivantamab plus lazertinib compared to osimertinib (HR, 0.80; 95% CI, 0.61-1.05; P =.11).
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 75% of patients in the amivantamab-lazertinib arm and 43% in the osimertinib arm. The rate of serious TEAEs was 49% and 33%, respectively. Eight patients in the amivantamab-lazertinib arm and 7 in the osimertinib arm had fatal TEAEs.
The rate of venous thromboembolism (VTE) was higher in the amivantamab-lazertinib arm than in the osimertinib arm — 37% and 9%, respectively. There were 2 fatal VTEs (0.5%) in each treatment arm. The median time to onset of the first VTE was 84 days with amivantamab plus lazertinib and 194 days with osimertinib.
“Most VTEs were grade 1 or 2,” Dr Cho noted. “The incidences of grade 4 or 5 VTEs were low and comparable between arms. Rates of discontinuations due to VTE were low and comparable between arms.”
At the time of their first VTE, most patients were not taking anticoagulants, Dr Cho added. Prophylactic anticoagulation is now recommended for the first 4 months of treatment in ongoing trials of amivantamab plus lazertinib, he said.
Disclosures: This research was supported by Janssen Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Cho BC, Felip E, Spira AI, et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Presented at ESMO Congress 2023. Oct. 20-24, 2023. Madrid, Spain. Abstract LBA14.
This article originally appeared on Cancer Therapy Advisor
