The cancer-free survival period is two years long! Chinese innovative drug targeted adjuvant treatment of lung cancer, Professor Zhou Caicun and Professor He Jianxing led the research and published "The Lancet-Respiratory Diseases"

▎Editor of WuXi AppTec's content team Although patients with early-stage non-small cell lung cancer (NSCLC) have the opportunity to completely remove the tumor, the probability of recurrence and metastasis is still very high.
About 50% of patients survive less than 5 years, and the effect of adjuvant chemotherapy is limited
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In East Asian patients with locally advanced or metastatic NSCLC, about 50% will develop EGFR mutations
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In patients with EGFR-mutant NSCLC, postoperative EGFR-TKIs targeted adjuvant therapy has attracted attention in recent years, and studies have shown that it is more helpful to improve disease-free survival than adjuvant chemotherapy
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Recently, "The Lancet-Respiratory Diseases" published the research results of Icotinib EVIDENCE, highlighting the recognition of the post-treatment application of Icotinib in the international academic arena.
This research also brings to China's early stage NSCLC patients with EGFR mutations.
New options for important treatments
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Screenshot source: The Lancet Respiratory Medicine EVIDENCE study shows that after radical surgery in patients with stage II-IIIA EGFR-mutant NSCLC, compared with standard adjuvant chemotherapy, adjuvant icotinib significantly prolongs disease-free survival (DFS) and has Better tolerance
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The study was carried out in 29 hospitals in China.
Professor Zhou Caicun of Shanghai Pulmonary Hospital and Professor He Jianxing of the First Affiliated Hospital of Guangzhou Medical University were the co-corresponding authors.
Professor He Jianxing and Professor Su Chunxia, ​​deputy director of the Department of Oncology of Shanghai Pulmonary Hospital, were the co-authors.
One author
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Based on the EVIDENCE research evidence, in June 2021, icotinib as a new indication for postoperative adjuvant treatment of stage II-IIIA EGFR-mutant NSCLC has been approved for marketing in China.
According to Betta Pharmaceutical News, this is also a global The first generation of EGFR-TKI adjuvant targeted therapy for NSCLC indications after surgery
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Image source: 123RF Icotinib is a class 1 innovative drug developed by Betta Pharmaceuticals over the past ten years.
It is a potent and highly selective oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
)
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Previously, Icotinib has been approved as a single-agent treatment for first-line treatment of locally advanced or metastatic NSCLC patients with sensitive mutations in the EGFR gene
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This study further explored the effect of icotinib in adjuvant treatment after radical surgery
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The EVIDENCE is a multi-center, randomized, open-label Phase 3 trial, and the results of the interim analysis are published this time
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From June 8, 2015 to August 2, 2019, a total of 322 patients with stage II-IIIA NSCLC who had undergone radical surgery and had mutations in exon 19 or exon 21 of the EGFR gene were randomized 1:1 Receive oral icotinib (125 mg three times a day for two years, n=161) or standard adjuvant chemotherapy-4 cycles of intravenous chemotherapy (vinorelbine + cisplatin for adenocarcinoma or squamous carcinoma; or Peimer Trexet + Cisplatin is used for non-squamous cell carcinoma, n=161)
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Follow-up until the patient relapses, intolerance or death
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Among them, 151 patients in the icotinib group and 132 patients in the chemotherapy group were included in the complete analysis set.
These patients had received at least one study drug treatment and did not violate the inclusion criteria
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The primary endpoint of the longer cancer-free survival study is the disease-free survival of the complete analysis set
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As of the data analysis, the median follow-up time was 24.
9 months.
Of the 151 patients in the icotinib group (26%), 58 of the 132 patients in the chemotherapy group (44%) had disease recurrence or death
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The median disease-free survival of the icotinib group was 47.
0 months (95% CI 36.
4-not reached), the chemotherapy group was 22.
1 months (95% CI 16.
8-30.
4), and the icotinib group had disease recurrence or death The risk was significantly reduced by 64% (HR=0.
36 [95%CI 0.
24-0.
55], p<0.
0001)
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▲Disease-free survival of adjuvant icotinib therapy (blue line) and adjuvant chemotherapy (red line)
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(Image source: Reference [1]) In the secondary endpoint, the 3-year disease-free survival rate of the icotinib group was also significantly higher than that of the chemotherapy group (63.
9% vs 32.
5%)
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Disease-free survival benefits have been observed in most subgroups of patients, including patients with stage II–IIIA, T2–T4, and N0–N2, as well as patients of different ages, genders, and smoking history
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In the icotinib group, brain recurrence was the most common (7% [11 cases/151 cases]), which was similar to the findings of other previous EGFR-TKIs adjuvant therapy studies; in the chemotherapy group, the local area was the most common site of recurrence (14% [18 cases/132 cases])
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As of the time of data analysis, overall survival data is still accumulating
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There were 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy group
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In the complete analysis set, although the two groups have not yet reached the median overall survival, the overall survival curve trajectory of the icotinib group is always higher than that of the chemotherapy group, which is similar to the disease-free survival curve, although this difference is not significant (HR 0.
91[ 95% CI 0.
42–1.
94])
.

Moreover, the research team pointed out in the paper that although the impact on overall survival has not been determined, the additional 2 years of cancer-free survival may be of psychological significance to patients
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The better tolerability safety analysis was carried out in patients who received at least one dose of icotinib or chemotherapy drugs, including 156 patients in the icotinib group and 139 patients in the chemotherapy group
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Adverse events of any grade occurred in 89% of patients in the icotinib group and 98% in the chemotherapy group
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11% of patients in the icotinib group and 61% of patients in the chemotherapy group reported adverse events of grade 3 or more severe
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Treatment-related serious adverse events occurred in 1% of the icotinib group and 14% of the chemotherapy group
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No interstitial pneumonia or treatment-related deaths were observed in either group
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The most common grade 3 or 4 treatment-related adverse event in the icotinib group was skin rash (3 cases [2%]), which was not observed in the chemotherapy group
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The most common grade 3 or 4 treatment-related adverse events in the chemotherapy group were neutropenia (57 cases [41%]), leukopenia (27 cases [19%]), and vomiting (18 cases [13%] ) And nausea (10 cases [7%]).
These reactions were not observed in the icotinib group
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The paper pointed out that icotinib has been shown to be safe and tolerable in patients with advanced NSCLC, and the severity of adverse events recorded in this trial is consistent with that reported in previous studies
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Compared with other first-generation EGFR-TKI treatments, patients treated with icotinib reported fewer serious treatment-related adverse events, especially interstitial lung disease
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Comparison with other adjuvant therapy studies The research team also discussed the comparison of adjuvant therapy with icotinib and other adjuvant therapy studies
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The ADAURA study showed that regardless of whether patients with early-stage EGFR-mutant NSCLC received adjuvant chemotherapy, on this basis, the disease-free survival benefit of adjuvant osimertinib was significantly better than that of placebo
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Unlike the ADAURA study, the EVIDENCE study aims to verify that icotinib may replace chemotherapy in adjuvant therapy
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Both the ADJUVANT study (gefitinib) and the EVAN study (erlotinib) support that in EGFR-mutant NSCLC, EGFR-TKI adjuvant therapy can improve disease-free survival compared with standard chemotherapy
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In the EVIDENCE study, the median disease-free survival (47 months) of the icotinib group was similar to that of the EVAN study (42.
4 months) and longer than that of the ADJUVANT study (28.
7 months)
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Further analyzing the survival curves of these three similar studies, the research team pointed out: In the EVIDENCE study, the survival curve began to separate at 6 months, which was similar to the ADJUVANT study and the EVAN study; but in the EVIDENCE study, the disease-free survival curve was only about 3 years old.
The disease-free survival curves of the ADJUVANT study and the EVAN study began to converge after about 24 months
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This suggests that icotinib may bring better disease-free survival improvement
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Of course, the paper has repeatedly emphasized that it is difficult to directly compare data across trials and requires careful interpretation
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Image source: 123RF Adjuvant Therapy New Choice Research Team pointed out that on the basis of previous EGFR-TKIs adjuvant therapy research, the results of this trial further show that in stage II-IIIA EGFR-mutant NSCLC, adjuvant therapy with icotinib is comparable to chemotherapy It has clinical potential, can improve disease-free survival, has better safety and tolerability, and will provide these patients with a new treatment option
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Next, the research team will further follow-up to observe whether the benefit of disease-free survival will translate into an overall survival benefit
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In addition, the choice of two-year medication cycle for icotinib is based on previous studies suggesting that many patients will relapse within two years
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However, the optimal duration of EGFR-TKI adjuvant therapy still needs further analysis
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In response to this medication problem, another randomized study (NCT01929200) of the adjuvant therapy strategy of icotinib is underway
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I look forward to more evidence to promote the renewal of NSCLC adjuvant treatment strategies, and hope that more patients can get hope of survival from the earlier application of targeted drugs! Related reading The disease control rate is 93.
4%! Led by Professor Lu Shun, the new choice of MET targeted therapy for lung cancer is listed in "The Lancet-Respiratory Diseases" and Professor Wu Yilong: 75.
5 months! One of the longest survival periods of targeted adjuvant therapy for lung cancer! The final survival results of CTONG1104 are published, and the risk of early lung cancer recurrence/death is reduced by 83%! Can osimertinib change clinical practice and target precision therapy earlier and neoadjuvant targeted therapy for lung cancer can prolong overall survival? Professor Wu Yilong ASCO announced reference materials[1] Jianxing He, et al.
, (2021).
Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open- label, phase 3 trial.
The Lancet Respiratory Medicine, DOI: https://doi.
org/10.
1016/S2213-2600(21)00134-X[2] Heavy! The research results of Betta Pharmaceuticals Icotinib EVIDENCE were published in "The Lancet·Respiratory Medicine".
Retrieved July 20, 2021, from http:// Note: Purpose of this article Introducing the progress of medical and health research, not a treatment plan recommendation
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If you need guidance on treatment plans, please go to a regular hospital for treatment
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