Janssen's RYBREVANT® (amivantamab) combined with chemotherapy has demonstrated a positive trend in overall survival (OS) for adult patients with previously treated non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. The Phase 3 MARIPOSA-2 study results, presented at the European Society of Medical Oncology (ESMO) 2024 Congress, indicate consistent benefit across post-progression outcomes compared to chemotherapy alone.
Improved Survival Outcomes
At the second interim analysis, with a median follow-up of 18.1 months, 50% of patients treated with amivantamab plus chemotherapy were alive at 18 months, compared to 40% in the chemotherapy-only arm (median OS: 17.7 vs. 15.3 months; HR, 0.73; 95% CI, 0.54–0.99; nominal P = 0.039). This suggests a clinically meaningful improvement in survival for patients receiving the combination therapy.
"The positive overall survival trend seen in MARIPOSA-2 suggests that amivantamab combined with chemotherapy could potentially change the treatment landscape for a population that has historically faced limited options," said Prof. Sanjay Popat, FRCP, Ph.D., Medical Oncologist at the Royal Marsden Hospital and the Institute of Cancer Research.
Significant Improvements in Treatment Discontinuation and Disease Progression
The study also revealed that amivantamab plus chemotherapy significantly improved treatment discontinuation rates. Nearly five times as many patients remained on the amivantamab combination therapy at 18 months (22%) compared to chemotherapy alone (4%) (median time-to-treatment discontinuation [TTD], 10.4 vs 4.5 months, respectively; 95% CI, 0.33–0.53; nominal P < 0.0001).
Patients receiving amivantamab plus chemotherapy experienced a 27% reduction in the risk of symptomatic progression (median time to symptomatic progression [TTSP], 16.0 vs 11.8 months; HR, 0.73; 95% CI, 0.55–0.96; nominal P = 0.026). The time to subsequent therapy was significantly prolonged with the amivantamab combination compared to chemotherapy (median time to subsequent therapy [TTST], 12.2 vs 6.6 months, respectively; HR, 0.51; 95% CI, 0.39–0.65; nominal P < 0.0001), reducing the risk of second disease progression or death by 36% (median progression-free survival 2 [PFS2], 16.0 vs 11.6 months, respectively; HR, 0.64; 95% CI, 0.48–0.85; nominal P = 0.002).
Safety Profile
Grade 3 or higher adverse events (AEs), mainly due to haematologic toxicities, were reported in 72% of patients treated with amivantamab plus chemotherapy and 48% with chemotherapy alone. Common Grade 3 or higher AEs included neutropenia, thrombocytopenia, anaemia, and leukopenia. Serious treatment-emergent AEs (TEAEs) were observed in 32% of patients treated with amivantamab plus chemotherapy and 20% with chemotherapy alone. Infusion-related reactions occurred in 58% (all grades) of patients on amivantamab plus chemotherapy. Treatment-related AEs leading to death were infrequent in all arms (2% vs. 0.4%) in the amivantamab plus chemotherapy and chemotherapy alone arms respectively. Permanent discontinuation of all study agents in amivantamab plus chemotherapy arm due to adverse reactions occurred in 11 (8 percent) patients.
Regulatory Status and Future Directions
In August 2024, the European Commission approved amivantamab plus chemotherapy for treating adults with advanced NSCLC with EGFR ex19del or L858R mutations after failure of prior therapy, including an EGFR tyrosine kinase inhibitor (TKI), based on the MARIPOSA-2 study.
"We are pleased to see that amivantamab plus chemotherapy continues to show improved survival outcomes after a year and a half of follow-up, providing real benefits to patients with few other options," said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. "These results underscore the potential of this combination regimen to make a meaningful difference for patients, and we anticipate continued improvement as we move toward the final analysis."
