TL;DR
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In a single-arm phase II trial, a three-drug regimen without chemotherapy produced a median progression-free survival of 10.9 months among patients with EGFR-mutant advanced lung cancer whose disease progressed on a third-generation EGFR inhibitor. The results are encouraging but do not establish that the combination is better than chemotherapy or other treatments; randomized studies are needed, and side effects were common.
A chemotherapy-free combination of amivantamab, lazertinib and bevacizumab showed antitumor activity in a phase II trial of patients with EGFR-mutant advanced non-small cell lung cancer that had progressed after treatment with a third-generation EGFR inhibitor. The single-arm study reported median progression-free survival of 10.9 months, but it cannot determine whether the regimen works better than chemotherapy or other available treatments.
The ETOP 18-21 AMAZE-lung trial enrolled 61 patients at 17 European sites. At 12 weeks, the objective response rate was 33%; the best overall response rate was 39%, meeting the study’s primary outcome. Researchers reported a median duration of response of 13.9 months and updated median overall survival of 19.9 months.
The trial tested the three drugs together after patients’ cancer progressed on a third-generation EGFR tyrosine kinase inhibitor (TKI). Amivantamab targets EGFR and MET, lazertinib is an EGFR TKI, and bevacizumab targets a pathway involved in blood vessel growth. The researchers said the combination is intended to address multiple pathways associated with cancer growth and treatment resistance.
Treatment-related side effects were frequent. The most common were infusion-related reactions, reported in 58%, and acneiform rash, reported in 50%. Grade 3 or 4 treatment-related adverse events occurred in 43%; serious treatment-related events occurred in 20%. Treatment interruptions, dose reductions and permanent discontinuations were reported in 67%, 37% and 20% of patients, respectively. Researchers reported no treatment-related deaths.
A Potential Option After TKI Resistance
Resistance to third-generation EGFR TKIs, including osimertinib and lazertinib, is a common challenge in advanced EGFR-mutant lung cancer. When disease progresses, patients and clinicians need further treatment options. The trial’s response and progression-free survival results suggest that combining drugs aimed at EGFR, MET and angiogenic pathways may offer sustained disease control for some patients without chemotherapy.
That possibility needs to be weighed against the study’s limits and the treatment burden. Yun Fan, an oncologist at Zhejiang Cancer Hospital who wrote an accompanying comment, said the duration of response and progression-free survival were among the longest reported in this treatment setting. But she also pointed to the gap between the 39% best overall response rate and the longer progression-free survival, and said a lower-risk group of enrolled patients could help explain the survival result. These findings are not proof that the regimen should replace established care.
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Treatment After EGFR Inhibitors
Third-generation EGFR TKIs are standard first-line treatments for advanced NSCLC with common sensitizing EGFR mutations. Cancer can acquire resistance and progress on these drugs, prompting consideration of subsequent treatment. The AMAZE-lung trial evaluated a chemotherapy-sparing approach in that setting, but its results need comparison with other options.
Earlier phase III studies provide relevant benchmarks. In MARIPOSA, amivantamab plus lazertinib improved progression-free survival by about seven months compared with osimertinib when used as first-line treatment. In MARIPOSA-2, amivantamab-based combinations with chemotherapy improved median progression-free survival by about two to four months compared with chemotherapy after progression on first-line osimertinib. Those trials involved different treatment settings and designs, so their results cannot be directly compared with AMAZE-lung.
The AMAZE-lung study enrolled patients between March 2023 and May 2024. It was a single-arm phase II trial: everyone received the triplet, with no randomized comparison group. The research team assessed the regimen against a historical response-rate benchmark rather than testing it directly against a current standard treatment.
“The trial provides preliminary evidence for the potential benefit of combined amivantamab, lazertinib, and bevacizumab.”
— Rolf A. Stahel and colleagues, the AMAZE-lung investigators
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What the Trial Cannot Establish
The study had no randomized control group, so it cannot show whether the triplet improves outcomes compared with chemotherapy or another regimen. Fan also questioned the historical benchmark used to plan the trial: she said it was based on early amivantamab monotherapy data and may not reflect more recent response rates for chemotherapy or newer combinations. Comparisons with results from separate trials should be treated cautiously because the patient groups and study designs differ.
It is also not clear which patients are most likely to benefit, how the regimen’s benefits and risks compare with current treatments, or whether the results will be confirmed in a larger study. The reported side effects, including venous thromboembolism in 17% of patients at any grade and 3% at grade 3 or 4, add to questions about tolerability. Fan described the clotting risk as a substantial treatment burden, noting that most participants received preventive anticoagulation.
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Randomized Evidence Is Needed
The next step is further study with a randomized comparison against an appropriate standard treatment. Such research could clarify whether the triplet extends disease control or survival, identify which patients may benefit, and better define the trade-off between outcomes and side effects. The investigators said randomized studies are needed; the source report does not identify a specific trial timeline or confirm that a follow-up study has begun.
Until comparative evidence is available, these phase II results are best understood as a signal of possible activity rather than proof of a new standard. Treatment decisions remain specific to each patient’s cancer and clinical circumstances and should be discussed with an oncology team.
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Key Questions
What combination did the trial test?
It tested amivantamab, lazertinib and bevacizumab in patients with EGFR-mutant advanced non-small cell lung cancer that had progressed after a third-generation EGFR inhibitor.
How long was median progression-free survival?
Researchers reported a median progression-free survival of 10.9 months. Because the trial had no randomized comparison group, that figure does not show how the regimen compares with other treatments.
Did the study prove the combination is better than chemotherapy?
No. This was a single-arm phase II trial, with no group assigned to chemotherapy or another treatment. Randomized research is needed to make a direct comparison.
What side effects were reported?
Infusion-related reactions and acneiform rash were the most common treatment-related events. Grade 3 or 4 treatment-related events occurred in 43% of patients, and 20% had serious treatment-related events.
Is the regimen established as standard treatment?
The reported findings do not establish it as a standard treatment. The investigators said the results should be interpreted cautiously and that randomized studies are needed.
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