KEY TAKEAWAYS
- The PAPILLON phase III trial aimed to assess the efficacy and safety of amivantamab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced EGFR Exon 20 insertion-mutated NSCLC.
- The primary endpoint was PFS. Secondary endpoints included ORR, PFS2, OS, and safety.
- The results demonstrated that amivantamab plus chemotherapy significantly improved PFS in EGFR Ex20ins advanced NSCLC, making it the new first-line SoC.
Non-small cell lung cancer(NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutations can be effectively treated with targeted therapies. Some mutations, like Exon 20 insertions, have limited treatment options and develop resistance quickly. Additionally, MET plays a role in resistance to EGFR therapies.
For this study, researchers aimed to assess the efficacy and safety of amivantamab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced EGFR Exon 20 insertion-mutated NSCLC.
Treatment-naïve patients were randomly assigned in a 1:1 ratio to receive either amivantamab-chemotherapy (ami-chemo) or chemotherapy alone. The primary endpoint was progression-free survival (PFS), assessed by a blinded independent central review.
Secondary endpoints were objective response rate (ORR), PFS after the first subsequent therapy (PFS2), overall survival (OS), and safety. A provision for crossover to amivantamab monotherapy was permitted for patients in the chemotherapy arm upon disease progression.
About 308 patients were randomized (ami-chemo, 153; chemo, 155). The median age was 61/62 years, with 56/60% females, 64/59% Asians, and 23/23% with a history of brain metastases for ami-chemo/chemo, respectively.
At a median follow-up of 14.9 months, ami-chemo demonstrated a median PFS of 11.4 months (95% CI, 9.8–13.7) compared to 6.7 months (95% CI, 5.6–7.3) for chemo (HR, 0.40; 95% CI, 0.30–0.53; P<0.001). The 18-month PFS rate was 31% for ami-chemo vs 3% for chemo.
The PFS benefit of ami-chemo was consistent across subgroups.ORR was 73% (95% CI, 65–80) for ami-chemo vs 47% (95% CI, 39–56) for chemo (OR, 2.97; 95% CI, 1.84–4.79; P<0.001). Median PFS2 was not estimable for ami-chemo vs 17.2 months for chemo (HR, 0.49; 95% CI, 0.32–0.76; P=0.001).
In the interim OS analysis (33% maturity), there was a favorable trend for ami-chemo vs chemo (HR, 0.67; 95% CI, 0.42–1.09; P=0.106), despite 66% of chemo-randomized patients, whose disease had progressed, receiving second-line ami.
The most common treatment-emergent adverse events (TEAEs) (≥40%) for ami-chemo were neutropenia, paronychia, rash, anemia, infusion-related reactions, and hypoalbuminemia, with no new safety signals. The discontinuation of ami due to treatment-related AEs(TRAEs) was 7%.
The results demonstrated that amivantamab plus chemotherapy significantly improved PFS in EGFR Ex20ins advanced NSCLC, making it the new first-line standard of care(SoC).
Clinical Trial: https://clinicaltrials.gov/study/NCT04538664
Girard N, Park K, Tang K, Cho BC, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung J, Popat S, Dias J, Bhattacharya A, Agrawal T, Shreeve M, Knoblauch RE, Zhou C. Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study. Ann Oncol. 2023;34(suppl_2):S1254-S1335. doi: 10.1016/annonc/annonc1358. LBA5.
