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A single-arm phase II study found that amivantamab, lazertinib and bevacizumab had antitumor activity in EGFR-mutant advanced NSCLC that progressed after a third-generation EGFR inhibitor. Median progression-free survival was 10.9 months, but the trial had no control group and treatment-related adverse events were common.
A single-arm phase II trial found that a chemotherapy-sparing combination of amivantamab, lazertinib and bevacizumab produced durable responses in some patients with EGFR-mutant advanced non-small cell lung cancer whose cancer progressed after a third-generation EGFR inhibitor. Median progression-free survival was 10.9 months, but the study had no comparison group, so it cannot establish whether the regimen is better than other treatment options.
In the ETOP 18-21 AMAZE-lung trial, the 12-week objective response rate was 33% and the best overall response rate was 39%. The study met its primary outcome, which tested the response rate against a historical benchmark. Median duration of response was 13.9 months. Updated results showed median overall survival of 19.9 months.
The trial enrolled 61 patients at 17 European sites between March 2023 and May 2024. Participants had advanced NSCLC that had progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI). The researchers, led by Rolf A. Stahel of the ETOP IBCSG Partners Foundation in Bern, Switzerland, reported the results in Lancet Respiratory Medicine.
Treatment-related side effects were frequent. The most commonly reported were infusion-related reactions, affecting 58% of patients, and acneiform rash, affecting 50%. Grade 3 or 4 treatment-related adverse events occurred in 43%, and serious treatment-related events in 20%. Side effects led to treatment interruptions in 67%, dose reductions in 37% and permanent discontinuation in 20%. No treatment-related deaths were reported.
A Possible Option After EGFR Resistance
The findings address a treatment challenge for people whose EGFR-mutant cancer progresses despite a third-generation TKI: resistance and renewed disease growth are common, and the next treatment choice matters. The triplet combines drugs aimed at EGFR, MET and angiogenic pathways, offering a chemotherapy-sparing approach that researchers say warrants further study.
The reported median progression-free survival and duration of response were among the longest reported in this setting, according to the study authors and an accompanying comment. Those figures could be encouraging for patients seeking options after resistance. But they do not show that the regimen extends life or controls disease better than chemotherapy or another established treatment; the study was not designed to make that comparison.
The potential benefit also needs to be weighed against treatment burden. Venous thromboembolism related to treatment was reported in 17% of patients at any grade and 3% at grade 3 or 4. Commentator Yun Fan of Zhejiang Cancer Hospital noted that this rate was concerning in light of the fact that most patients received preventive anticoagulation. The high frequency of interruptions and dose changes also shows that tolerability is part of the clinical picture.
EGFR mutation lung cancer treatment
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Treatment After TKI Progression
Third-generation EGFR TKIs, including osimertinib and lazertinib, are standard first-line treatments for advanced NSCLC with common sensitizing EGFR mutations. Although these medicines can control cancer, tumors can acquire resistance and progress. The trial examined a different combination for patients at that stage, rather than testing the triplet as initial therapy.
Amivantamab, an antibody targeting EGFR and MET, is approved with lazertinib for first-line treatment based on the phase III MARIPOSA trial. In that study, the combination improved median progression-free survival by about seven months compared with osimertinib alone. In MARIPOSA-2, adding amivantamab, with or without lazertinib, to second-line chemotherapy improved median progression-free survival by about two to four months compared with chemotherapy alone after progression on first-line osimertinib.
The AMAZE-lung regimen differs because it paired three targeted agents without chemotherapy. Its primary outcome was assessed against a historical objective response rate of 20%. Fan cautioned that this benchmark may be outdated: she cited response rates of 27% to 43% for contemporary platinum-based chemotherapy alone and rates above 50% for some combinations approved in recent years.
“The study provides “preliminary evidence for the potential benefit” of combined amivantamab, lazertinib and bevacizumab.”
— Rolf A. Stahel and colleagues
Limits of the Trial Evidence
The study was single-arm and included 61 patients, so it cannot show how the triplet compares directly with chemotherapy or other available regimens. Fan also questioned whether the historical response-rate benchmark used to judge the primary outcome reflects current treatment results. The modest response rate alongside longer progression-free survival needs further examination, she said.
The results also do not identify which patients are most likely to benefit, or establish how the combination compares on overall survival, quality of life or side effects with other treatments. The reported median overall survival of 19.9 months is an observed result in this study, not evidence that the regimen caused longer survival. Whether the findings apply to a broader and more diverse patient population is also uncertain.
Randomized Testing Is Needed
The investigators said randomized studies are needed to support the findings. A trial comparing the triplet with an appropriate standard treatment could clarify whether it improves disease control and whether any benefit justifies its side effects and treatment burden. Until such comparisons are available, the phase II results provide preliminary evidence rather than proof that the regimen should replace existing care.
For now, the study establishes reported activity in a selected group of patients after third-generation EGFR TKI progression. The source material does not identify a planned randomized trial or a date for further results, so the next clinical milestone remains unclear.
Key Questions
What drugs were used in the chemotherapy-sparing regimen?
The regimen combined amivantamab, lazertinib and bevacizumab, targeting EGFR, MET and angiogenic pathways. It was studied in patients with advanced EGFR-mutant NSCLC that progressed after a third-generation EGFR TKI.
How long did disease control last in the trial?
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 and do not show how the regimen compares with another treatment.
Did the regimen have serious side effects?
Grade 3 or 4 treatment-related adverse events occurred in 43% of patients, and serious treatment-related events in 20%. Treatment-related venous thromboembolism was reported in 17% at any grade; no treatment-related deaths were observed.
Does the study show the triplet is better than chemotherapy?
No. The trial had no randomized comparison group. Researchers and an accompanying commentator said randomized studies are needed to determine how the regimen compares with current treatment options.
Source: rss
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