PAPILLON finds longer survival with amivantamab in rare EGFR lung cancer

Final results from the phase III, randomized controlled PAPILLON trial show that adding amivantamab to chemotherapy produced durable clinical benefit in people with advanced non-small cell lung cancer harboring an EGFR exon 20 insertion mutation. Median overall survival was 34.3 months in the amivantamab-plus-chemotherapy group, compared with 27.9 months in the chemotherapy-alone group, a difference of about six months. The final overall-survival analysis did not reach statistical significance, however. Investigators attributed the limitation partly to limited statistical power for that endpoint and substantial crossover: about three-quarters of eligible patients initially assigned to chemotherapy subsequently received amivantamab after their cancer progressed. The results were presented by Chul Kim, MD, MPH, of Georgetown University’s Lombardi Comprehensive Cancer Center, during a presidential plenary at the 2026 World Conference on Lung Cancer in Seoul.

The overall-survival finding followed the PAPILLON trial’s previously reported progression-free survival benefit, which led to U.S. Food and Drug Administration approval of amivantamab, marketed as Rybrevant, in March 2024. In the final reported results, median progression-free survival—the period without significant cancer growth or death—was 11.4 months among patients receiving amivantamab plus chemotherapy, compared with 6.7 months among those receiving chemotherapy alone. The combination reduced the risk of disease progression by 60%. Objective response rates, defined as the percentage of patients whose cancer shrank or disappeared after treatment, were 73% in the amivantamab arm and 40% in the chemotherapy-alone arm. Patient-reported quality-of-life outcomes also favored the amivantamab arm. PAPILLON was conducted at Georgetown University’s Lombardi Comprehensive Cancer Center and 231 other international sites.

Kim said the 34.3-month median represented the longest median overall survival reported to date for people with this form of lung cancer, compared with a historical estimate of approximately 1.5 to two years. He emphasized that the final analysis did not meet the threshold for statistical significance and that the trial had limited statistical power for overall survival. The power was further reduced because most eligible patients in the chemotherapy group crossed over to amivantamab after progression. According to Kim, accounting for that crossover made the overall-survival benefit much more pronounced, although the source report did not provide a numerical adjusted survival estimate. Taken together with the progression-free survival and response findings, the results further supported amivantamab plus chemotherapy as a foundational first-line treatment for patients with advanced EGFR exon 20 insertion-mutant non-small cell lung cancer.

EGFR exon 20 insertion mutations occur in approximately 1% to 2% of advanced non-small cell lung cancers, corresponding to an estimated 1,500 to 2,500 diagnoses annually in the United States. The mutations also account for about 5% to 10% of EGFR-mutated non-small cell lung cancers. The investigators emphasized next-generation sequencing as a way to identify rare genomic alterations such as EGFR exon 20 insertions and match patients with therapies directed against their tumors. The report said this type of genomic testing is routinely used at Georgetown Lombardi and other comprehensive cancer centers. Researchers are now investigating amivantamab-based strategies in atypical EGFR-mutant non-small cell lung cancer and other tumor types, including head and neck and colorectal cancers. The global PAPILLON trial was led by Kim and co-investigators from Institut Curie and Paris-Saclay University, Shanghai Pulmonary Hospital at Tongji University School of Medicine, Yonsei Cancer Center at Yonsei University College of Medicine, and Samsung Medical Center at Sungkyunkwan University School of Medicine. The clinical trial was supported in part by Janssen Research & Development, a Johnson & Johnson company, and Kim disclosed consulting relationships with multiple pharmaceutical and diagnostics companies, including Johnson & Johnson.

Subject of Research: Final overall-survival analysis of amivantamab plus chemotherapy in advanced EGFR exon 20 insertion-mutant non-small cell lung cancer.

Article Title: Georgetown investigator presents final PAPILLON trial results showing long-term survival in a subset of lung cancer

Article References: Georgetown investigator presents final PAPILLON trial results showing long-term survival in a subset of lung cancer. Original publication (Bibliographic details unavailable.)

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Keywords: PAPILLON trial, amivantamab, EGFR exon 20, non-small cell lung cancer, overall survival, progression-free survival, randomized trial, targeted therapy, treatment crossover, Georgetown University, Georgetown, investigator