Plain language summary of PAPILLON: amivantamab plus chemotherapy in untreated EGFR-mutated non-small-cell lung cancer

What is this summary about?: This is a plain language summary of an article that describes the first results of the phase 3 PAPILLON study in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with Exon 20 insertion (Ex20ins) mutations in the epidermal growth factor receptor (EGFR) gene who had not had any cancer treatment before. Researchers looked at how safe and effective the bispecific antibody amivantamab (brand name: RYBREVANT^®) plus chemotherapy was in comparison to chemotherapy alone. Amivantamab was approved by the US Food and Drug Administration (FDA) in May 2021 for patients with the same type of cancer who got worse after chemotherapy. In March 2024, amivantamab was approved in combination with chemotherapy for previously untreated patients with the same type of cancer. The National Comprehensive Cancer Network^® (NCCN^®) recommends amivantamab plus chemotherapy as a preferred first treatment option for these patients. What were the results?: 308 patients were randomly selected to receive amivantamab plus chemotherapy or chemotherapy alone. Patients who received amivantamab plus chemotherapy lived longer without having their disease get worse compared to those who had chemotherapy. Patients who had amivantamab plus chemotherapy also had the risk of their disease getting worse or dying reduced by 60% compared to chemotherapy. After 18 months of treatment, 31% of patients on amivantamab plus chemotherapy did not have their cancer grow or spread compared to 3% with chemotherapy. More than 7 in 10 patients who had amivantamab plus chemotherapy had tumors that shrank by at least 30% or were no longer detectable. This only happened in less than 5 in 10 patients who had chemotherapy alone. All patients had side effects, with the most common being neutropenia (occurring in 59% of patients), paronychia (56%), and rash/red skin bumps (54%/31%) for those treated with amivantamab plus chemotherapy, and anemia (55%), neutropenia (45%), and nausea (42%) for those treated with chemotherapy. Few patients (7%) stopped taking amivantamab due to side effects. What do the results mean?: Amivantamab plus chemotherapy worked well to extend the time that patients' cancer did not worsen. Patients had a 60% lower risk of death or having their cancer worsen compared to those who had chemotherapy. These benefits were seen in groups of patients with different characteristics. Amivantamab plus chemotherapy works well, is well tolerated, and is a good treatment option for untreated patients who have advanced NSCLC with EGFR Ex20ins mutations.