Cancer Treatment Today

though the drug Rybrevant RYBREVANT is a bispecific EGF receptor-directed and MET receptordirected antibody indicated for the treatment of adult patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal
growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an
FDA-approved test, whose disease has progressed on or after platinum-based
chemotherapy, in this case the mutation is in exon 19. The patient had not failed plaitn based therapy, and in fact, it will be given with carboplatin.
There is some evidence that this drug might work for EGFR exon 19 as well ( Bazhenova et al) but this remaisn to be onfirmed.
However, the theee drug proposed regimen had been studied. he Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data from the Phase 3 PAPILLON study showing that first-line treatment with RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy (carboplatin-pemetrexed) resulted in a 60 percent reduction in the risk of disease progression or death (Hazard Ratio [HR]=0.395; 95 percent Confidence Interval [CI], 0.30–0.53; p value P<0.0001) in patients with previously untreated advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, compared to chemotherapy alone. Results also showed treatment with RYBREVANT® plus chemotherapy significantly improved objective response rate (ORR) and progression-free survival (PFS) after first subsequent therapy (PFS2). These data were presented in a Presidential Symposium at the European Society of Medical Oncology (ESMO) 2023 Congress taking place October 20-24, 2023 in Madrid, Spain (Abstract #LBA5) and simultaneously published in The New England Journal of Medicine.
This is nto exactly first-line tehrpay, but it is first time chemotherpay is being used.
Treatment with RYBREVANT® plus chemotherapy resulted in longer PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR) compared with chemotherapy alone. At a median follow-up of 14.9 months, PFS was significantly prolonged for patients who received RYBREVANT® plus chemotherapy than for those who received chemotherapy alone (median, 11.4 months and 6.7 months, respectively; HR for disease progression or death=0.395; 95 percent CI, 0.30–0.53; P<0.0001). At 18 months, 31 percent of patients receiving RYBREVANT® plus chemotherapy remained alive and progression-free compared to 3 percent for patients receiving chemotherapy alone. Treatment with RYBREVANT® plus chemotherapy showed consistent PFS benefit across patient subgroups. An ORR of 73 percent (95 percent CI, 65–80) was observed for the combination of RYBREVANT® and chemotherapy compared to 47 percent (95 percent CI, 39–55) in patients receiving chemotherapy alone. Median PFS2 was longer with RYBREVANT® plus chemotherapy compared to chemotherapy alone (HR=0.493; 95 percent CI, 0.32–0.76; P=0.001), supporting the potential first-line use of RYBREVANT® and chemotherapy.

Girard et al. Amivantamab Plus Carboplatin/Pemetrexed vs Carboplatin/Pemetrexed as First line Treatment in EGFR Exon 20 Insertion-mutated Advanced Non-small Cell Lung Cancer (NSCLC): Primary Results From PAPILLON, a Randomized Phase 3 Global Study. ESMO 2023. October 21, 2023.

Bazhenova L, Minchom A, Viteri S, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung Cancer. 2021;162:154-161. doi:10.1016/j.lungcan.2021.10.020