Phase III Trial Supports Use of Amivantamab in NSCLC With EGFR Exon 20 Insertions

By: Celeste L. Dixon
Posted: Thursday, February 1, 2024

Intravenous amivantamab plus chemotherapy was significantly superior in efficacy to chemotherapy alone in patients with advanced non–small cell lung cancer (NSCLC) who had EGFR exon 20 insertions receiving first-line treatment, according to the results of the randomized phase III PAPILLON trial involving more than 300 participants. In The New England Journal of Medicine, Caicun Zhou, MD, PhD, of Tongji University School of Medicine, Shanghai, and colleagues reported that progression-free survival—the primary outcome—was significantly longer with the bispecific monoclonal antibody plus chemotherapythan with chemotherapy alone (median, 11.4 months vs 6.7 months; P < .001).

Further, 18-month progression-free survival in the combination group was 31% vs 3% in the chemotherapy group, and a complete or partial response at data cutoff was reported in 73% and 47%, respectively (P < .001). The progression-free survival benefit was reported across all prespecified subgroups, categorized by race, age, sex, smoking history, Eastern Cooperative Oncology Group performance status score, and brain metastasis history, the team noted.

The predominant adverse events associated with the amivantamab combination were reversible hematologic and EGFR-related toxicities. Adverse reactions caused 7% of patients to discontinue amivantamab. Chemotherapy for all patients consisted of carboplatin and pemetrexed.

In the interim overall survival analysis (33% maturity), the hazard ratio for death withamivantamab plus chemotherapy compared with chemotherapy alone was 0.67 (P = .11). Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy, the team noted.

“Our results support the value of testing patients with NSCLC for insertions in the EGFR exon 20 at the time of metastatic diagnosis,” Dr. Zhou and co-investigators emphasized. Unfortunately, “polymerase chain reaction assays miss 50% of such mutations because of the[assay’s] inability to capture the full variability of insertion-mutated subtypes.”

Disclosure: For full disclosure of the study authors, visit nejm.org.

The New England Journal of Medicine