Compared to chemotherapy alone, amivantamab plus chemotherapy had a better objective response rate and prolonged progression-free survival and overall survival.
Data from the randomized, open-label phase 3 PAPILLON study (NCT04538664) show that, compared to chemotherapy alone, first-line treatment with amivantamab-vmjw (Rybrevant; Janssen Pharmaceutical Companies) in combination with chemotherapy resulted in a reduction in the risk of disease progression or death in patients with previously untreated or advanced metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. These data were presented at the European Society of Medical Oncology (ESMO) 2023 Congress.
Receiving an FDA approval in May 2021, amivantamab is a bispecific antibody that targets EGFR and MET with immune cell-directing activity. It is indicated for the treatment of adult patients with local advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
"Patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive NSCLC are in need of targeted therapies that can be used earlier in the course of their disease, given the tendency for rapid progression and poor outcomes often seen with chemotherapy alone," said Kiran Patel, MD, vice president, clinical development, solid tumors, Janssen Research & Development, LLC, in a press release.
Investigators in the PAPILLON study evaluated the efficacy and safety of amivantamab in combination with chemotherapy (carboplatin-pemetrexed) compared with chemotherapy alone in newly diagnosed patients with advanced or metastatic NSCLC characterized by EGFR exon 20 insertion mutations. Further, patients who received chemotherapy alone were able to receive amivantamab monotherapy in the second-line setting after confirmation of disease progression.
The primary endpoint of the study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), PFS after first subsequent therapy, duration of response, time to subsequent therapy, and overall survival (OS).
Study results indicate that there was a 60% reduction in the risk of disease progression or death (hazard ratio [HR] = 0.395; 95% confidence interval [CI], 0.30-0.53; P < 0.0001) in patients treated with amivantamab plus chemotherapy. Further, at a median follow-up of 14.9 months, PFS was significantly prolonged in patients who received both amivantamab and chemotherapy compared to those who received chemotherapy alone. In addition, an ORR of 73% was observed in patients who received the combination therapy compared to the 47% ORR in patients who received chemotherapy alone.
Among the patients who received only chemotherapy, 71 of the 94 patients (76%) received subsequent amivantamab treatment as a second-line therapy. Further, OS was favorable for patients who were treated with amivantamab plus chemotherapy compared to those who received only chemotherapy (HR = 0.675; 95 percent CI, 0.42–1.09; P = 0.106), with 72% and 54%, respectively, alive at 2 years.
"We have seen promising outcomes with [amivantamab] in the second-line setting for patients with EGFR exon 20 insertion mutations following platinum-based chemotherapy. However, targeted therapy is generally used as a first-line treatment in other settings to address disease progression earlier and achieve optimal treatment outcomes for patients," said presenting author Nicolas Girard, MD, professor of respiratory medicine at Versailles Saint Quentin University and chair of medical oncology department at Institute Curie in Paris, in the press release. "The significant improvement in PFS and in other efficacy results observed in the PAPILLON study supports [amivantamab] plus chemotherapy as a potential future first-line regimen for these patients."
EGFR and MET-related toxicities that were observed in patients who were treated with amivantamab with chemotherapy were mostly grade 1 and 2 and included paronychia, rash, hypoalbuminemia, and peripheral edema. In both treatment groups, chemotherapy-associated hematologic and gastrointestinal complications were comparable except for a higher frequency of neutropenia for the amivantamab plus chemotherapy group. No new safety signals were observed with amivantamab, with the safety profile for the combination treatment arm being consistent with the safety profiles in the chemotherapy alone arm.
"PAPILLON is the first randomized phase 3 study to show clinically meaningful results for a targeted therapy in combination with chemotherapy—a regimen with the potential to become a practice-changing first-line treatment for these patients," said Patel in the press release.
Johnson & Johnson. New Data from Phase 3 PAPILLON Study Show RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy Resulted in 60 Percent Reduction in Risk of Disease Progression or Death in Patients with Previously Untreated EGFR Exon 20 Insertion Mutation-Positive Non-Small Cell Lung Cancer. News release. October 21, 2023. Accessed October 23, 2023. https://www.prnewswire.com/news-releases/new-data-from-phase-3-papillon-study-show-rybrevant-amivantamab-vmjw-plus-chemotherapy-resulted-in-60-percent-reduction-in-risk-of-disease-progression-or-death-in-patients-with-previously-untreated-egfr-exon-20-insertion-mutati-301963753.html