TL;DR
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A single-arm phase II trial found that amivantamab, lazertinib and bevacizumab had antitumor activity in advanced EGFR-mutant lung cancer that progressed after a third-generation EGFR inhibitor. Median progression-free survival was 10.9 months, but the study had no comparison group and side effects frequently led to treatment changes.
A chemotherapy-sparing combination of amivantamab, lazertinib and bevacizumab showed antitumor activity in a phase II study of people with EGFR-mutant advanced non-small cell lung cancer whose disease progressed after treatment with a third-generation EGFR inhibitor. The single-arm trial reported median progression-free survival of 10.9 months, but it cannot establish whether the regimen works better than other treatment options.
The ETOP 18-21 AMAZE-lung study enrolled 61 patients at 17 European sites. Participants had advanced cancer that had progressed after a third-generation EGFR tyrosine kinase inhibitor (TKI), such as osimertinib or lazertinib. The study’s primary outcome was the objective response rate at 12 weeks: 33% of patients had a response by that point, while the best overall response rate during the study was 39%.
Median duration of response was 13.9 months, and updated results showed median overall survival of 19.9 months. The researchers, led by Rolf A. Stahel of the ETOP IBCSG Partners Foundation in Bern, Switzerland, reported the results in The Lancet Respiratory Medicine. They described the findings as preliminary evidence for a three-drug approach aimed at the EGFR, MET and angiogenic pathways.
Side effects were common and often affected treatment. The most frequently reported treatment-related events were infusion reactions, in 58% of participants, and acneiform rash, in 50%. Grade 3 or 4 treatment-related events occurred in 43%; serious treatment-related events were reported in 20%. Treatment interruptions, dose reductions and permanent discontinuations occurred in 67%, 37% and 20% of patients, respectively. The researchers reported no treatment-related deaths.
A Possible Option After TKI Resistance
For patients whose cancer progresses after a third-generation EGFR TKI, treatment choices are shaped by the development of acquired resistance. The trial raises the possibility that targeting EGFR, MET and angiogenic signaling together could provide disease control without chemotherapy for some patients. That is a potential treatment strategy, not proof that chemotherapy can be avoided safely or effectively across this patient group.
Yun Fan of Zhejiang Cancer Hospital, writing in an accompanying comment, said the duration of response and progression-free survival were among the longest reported in this treatment setting. Fan also cautioned that the results need careful interpretation: a prolonged median progression-free survival alongside a more modest response rate could partly reflect a lower-risk group of enrolled patients, rather than the effect of the combination alone. The study’s adverse-event burden also matters when weighing a chemotherapy-sparing approach.
EGFR-mutant lung cancer treatment medications
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Treatment After EGFR Inhibitors
Third-generation EGFR TKIs, including osimertinib and lazertinib, are standard first-line treatments for advanced NSCLC with common sensitizing EGFR mutations. Cancer can acquire resistance to these drugs, after which treatment decisions become more complex. Amivantamab targets EGFR and MET; bevacizumab acts on angiogenic pathways, while lazertinib is an EGFR TKI.
Other studies provide context but are not direct comparisons with AMAZE-lung. The phase III MARIPOSA trial found that first-line amivantamab plus lazertinib improved progression-free survival by about seven months compared with osimertinib alone. In MARIPOSA-2, amivantamab with or without lazertinib alongside standard second-line chemotherapy improved median progression-free survival by about two to four months compared with chemotherapy. Those trials used different treatment settings and designs, so their results do not establish how the chemotherapy-sparing triplet compares.
“The study provides preliminary evidence for the potential benefit of combined amivantamab, lazertinib, and bevacizumab.”
— Rolf A. Stahel and colleagues, reporting the AMAZE-lung trial
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The study had no randomized comparison group, so it cannot show whether the triplet improves outcomes over chemotherapy or another available regimen. Fan also questioned whether the study’s historical response-rate benchmark of 20% remains appropriate, noting that she cited response rates of 27% to 43% for contemporary platinum-based chemotherapy alone and rates above 50% for some newer combinations. These figures refer to other treatment evidence, not a head-to-head comparison with the triplet.
The results also do not identify which patients are most likely to benefit. The participant group was relatively small, and the trial included people with differing clinical characteristics. Treatment-related venous thromboembolism occurred in 17% of patients at any grade and was grade 3 or 4 in 3%; Fan described the risk as a substantial treatment burden, noting that most participants received preventive anticoagulation. Further evidence is needed to clarify both the balance of benefit and harm and the best place for the regimen in care.
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Randomized Trials Needed
The investigators said randomized studies are needed to support the findings. Such trials could compare the triplet with relevant treatment options, test whether the progression-free survival result holds in a broader group and provide a clearer assessment of side effects. The source report does not specify a next trial, its timeline or whether the regimen is being considered for a regulatory change.
For now, the phase II findings are evidence of activity, not a new standard of care. Clinicians and patients will need comparative data to judge whether the potential to delay progression justifies the frequency of treatment interruptions, dose reductions and discontinuations reported in AMAZE-lung.
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Key Questions
Which patients were studied?
The trial enrolled 61 people with advanced EGFR-mutant NSCLC whose cancer had progressed after a third-generation EGFR TKI.
What were the main results?
The 12-week objective response rate was 33%, and the best overall response rate was 39%. Median progression-free survival was 10.9 months and median duration of response was 13.9 months. These are results from a single-arm study, not a comparison with another treatment.
Was the regimen free of chemotherapy?
The tested combination of amivantamab, lazertinib and bevacizumab was chemotherapy-sparing. The findings do not show that it can replace chemotherapy for all patients.
What side effects were reported?
Infusion reactions occurred in 58% of participants and acneiform rash in 50%. Grade 3 or 4 treatment-related events occurred in 43%, and 20% permanently discontinued at least one study drug because of treatment-related adverse events.
Has the combination been shown to be better than chemotherapy?
No. AMAZE-lung had no randomized comparator. The investigators said randomized studies are needed to establish how the regimen compares with other treatments.
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