The addition of amivantamab to chemotherapy improved outcomes compared to chemotherapy alone as a first-line treatment for patients with EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC), according to phase 3 data presented at ESMO Congress 2023.
In the phase 1 CHRYSALIS study, researchers observed promising activity by combining chemotherapy with amivantamab, a bispecific antibody targeting EGFR and MET. In the phase 3 PAPILLON study, researchers randomly assigned previously untreated patients with EGFR Exon 20 insertion-mutated NSCLC to amivantamab plus carboplatin/pemetrexed chemotherapy or to chemotherapy alone.
Progression-free survival (PFS) served as the study’s primary endpoint. Secondary endpoints included PFS2, objective response rate (ORR), overall survival (OS), and safety. The study included data from 308 patients (amivantamab plus chemotherapy, n = 153; chemotherapy, n = 155). The median follow-up at the time of reporting was 14.9 months.
The researchers observed a significantly prolonged PFS interval among patients assigned to amivantamab plus chemotherapy (median, 11.4 months vs 6.7 months; hazard ratio [HR] = 0.4; 95% CI, 0.3-0.53; P < .001). The 18-month PFS rate for the combination was 31%, compared with 3% for chemotherapy alone. The ORR significantly favored amivantamab plus chemotherapy (73% vs 47%; odds ratio [OR] = 2.97; 95% CI, 1.84-4.79; P < .001), as did the median PFS2 (not reached vs 17.2 months; HR = 0.49; 95% CI, 0.32-0.75; P = .001).
OS data were not mature at the time of reporting. An interim OS analysis showed a favorable trend toward randomization to amivantamab plus chemotherapy (HR = 0.67; 95% CI, 0.42-1.09). However, the researchers noted that 66% of patients assigned to chemotherapy who experienced progression had received amivantamab in the second line.
Treatment with amivantamab plus chemotherapy was well tolerated, with a discontinuation rate of 7%. The most common treatment-related adverse events included neutropenia, paronychia, rash, anemia, infusion-related reactions, and hypoalbuminemia. The researchers observed no new safety signals.
“PAPILLON establishes amivantamab plus chemotherapy as the new first-line standard of care in EGFR Exon 20 insertion-mutated advanced NSCLC,” the researchers concluded.
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Disclosures: Some researchers declared financial ties to drugmakers. See full study for details. CHRYSALIS and PAPILLON were supported by Janssen.
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