AMAZE-lung: a chemotherapy-sparing triplet after third-generation EGFR inhibitor progression

Design

Prospective single-arm phase 2 trial, 17 European sites

Population

61 patients with EGFR-mutant non-squamous NSCLC after third-generation EGFR TKI progression

Primary outcome

12-week objective response rate in first 60 patients

Effect

33% (95.6% CI 21 to 47); grade 3 to 4 treatment-related adverse events 43%

AMAZE-lung was a single-arm, multicentre phase 2 trial across 17 European sites. It enrolled 61 adults with non-squamous NSCLC carrying EGFR exon 19 deletion or L858R, whose disease progressed on a third-generation EGFR inhibitor. They received amivantamab, lazertinib and bevacizumab until progression or toxicity. Median age was 65, and 30% had asymptomatic brain metastases.

The primary outcome was 12-week objective response in the first 60 patients: 20 responded (33%, 95.6% CI 21 to 47), which rejected the null rate of 20% or less. Overall, 39% (24 of 61) had a partial response. At a median 9.0 months of follow-up, 28 were still on treatment.

Grade 3 to 4 treatment-related adverse events occurred in 43% and serious events in 20%. Infusion reactions (58%) and acneiform rash (50%) were common, and venous thromboembolism of any grade occurred in 17% (grade 3 to 4 in 3%). There were no treatment-related deaths.

Without a control arm, the study cannot say whether this beats chemotherapy-based regimens. The authors call it promising.

• Response rate 33% at 12 weeks in a single-arm study; there was no comparison with chemotherapy-based options.
• Plan for infusion reactions, rash and thromboembolism if this regimen is used in a trial or approved setting.
• Follow-up was short (median 9 months), so durability is not established.
• Discuss options after EGFR inhibitor progression at a tumour board and ask about trial access.

Why it matters

Chemotherapy after targeted-therapy resistance is poorly tolerated by many patients, so a chemotherapy-free option is of interest.

Don't overread it

Phase 2, single-arm, 61 patients, short follow-up, and industry co-funded.

The statistics, in plain English

A 33% response rate with an interval of 21 to 47% is compatible with true responses from about one in five to nearly one in two. Single-arm trials cannot account for patient selection, so they show activity, not superiority.

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