Journal Article

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions

Boyer, Michael, Zhou, Caicun, Majem, Margarita, Kitazono, Satoru, Gumus, Mahmut, Park, Keunchil, Kim, Sang-we, Goldman, Jonathan W., Tang, Ke-Jing, Cheng, Susanna, Xie, John, Cho, Byoung Chul, Paz-Ares, Luis, Girard, Nicolas, Liu, Baogang, Hung, Jen-Yu, Knoblauch, Roland E., Bhattacharya, Archan, Mansfield, Aaron S., Felip, Enriqueta, Shreeve, S. Martin, Ono, Akira, Mourão Dias, Josiane, Sabari, Joshua K., Sanborn, Rachel E., Agrawal, Trishala, Popat, Sanjay, Thiagarajan, Muthukkumaran

2023

Overview

Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( ) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed. In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy. A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions. The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).

• Publisher: Massachusetts Medical Society
• Subject: Antineoplastic Agents, Immunological - administration & dosage / Antineoplastic Agents, Immunological - adverse effects / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Antitumor activity / Carboplatin / Carboplatin - administration & dosage / Carboplatin - adverse effects / Carboplatin - therapeutic use / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - pathology / Chemotherapy / Disease Progression / Epidermal growth factor receptors / ErbB Receptors - genetics / Exons - genetics / Humans / Hypothesis testing / Kinases / Ligands / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Metastasis / Monoclonal antibodies / Mutation / Non-small cell lung carcinoma / Pemetrexed - administration & dosage / Pemetrexed - adverse effects / Pemetrexed - therapeutic use / Protein Kinase Inhibitors - therapeutic use / Small cell lung carcinoma / Survival analysis / Targeted cancer therapy