The cancer-free survival period is two years long! Chinese innovative drug targeted adjuvant treatment of lung cancer

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 high.

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.

The EVIDENCE study showed that after radical surgery in patients with stage II-IIIA EGFR-mutant NSCLC, compared with standard adjuvant chemotherapy, adjuvant therapy with icotinib significantly prolonged disease-free survival (DFS) and was better tolerated

The research was carried out in 29 hospitals in China.

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.

Icotinib is a class 1 innovative drug developed by Betta Pharmaceuticals for nearly a decade.

The EVIDENCE is a multi-center, randomized, open-label Phase 3 trial, and the results of the interim analysis are published this time

Among them, 151 patients in the icotinib group and 132 patients in the chemotherapy group were included in the complete analysis set.

Longer cancer-free survival

The primary endpoint of the study is the disease-free survival of the complete analysis set

▲Disease-free survival of adjuvant icotinib therapy (blue line) and adjuvant chemotherapy (red line)

On 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.

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

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])

As of the time of data analysis, overall survival data is still accumulating

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

Better tolerated

The 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

Adverse events of any grade occurred in 89% of patients in the icotinib group and 98% in the chemotherapy group
.
11% of patients in the icotinib group and 61% of patients in the chemotherapy group reported adverse events of grade 3 or more severe
.
Treatment-related serious adverse events occurred in 1% of the icotinib group and 14% of the chemotherapy group
.
No interstitial pneumonia or treatment-related deaths were observed in either group
.

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
.
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
.

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
.
Compared with other first-generation EGFR-TKI treatments, patients treated with icotinib reported fewer serious treatment-related adverse events, especially interstitial lung disease
.

Comparison with other research on adjuvant therapy

The research team also discussed the comparison of adjuvant therapy with icotinib and other adjuvant therapy programs
.
The ADAURA study showed that regardless of whether patients with early EGFR-mutant NSCLC received adjuvant chemotherapy, on this basis, the benefit of adjuvant osimertinib for disease-free survival was significantly better than that of placebo
.
Unlike the ADAURA study, the EVIDENCE study aims to verify that icotinib may replace chemotherapy in adjuvant therapy
.

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
.
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)
.
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
.
This suggests that icotinib may bring better disease-free survival improvement
.

Of course, the paper has repeatedly emphasized that it is difficult to directly compare data across trials and requires careful interpretation
.

New options for adjuvant therapy

The research team pointed out that on the basis of previous studies on EGFR-TKIs adjuvant therapy, the results of this trial further show that in stage II-IIIA EGFR-mutant NSCLC, adjuvant icotinib therapy has clinical potential compared with chemotherapy and can improve Disease survival, with better safety and tolerability, will provide these patients with a new treatment option
.

Next, the research team will further follow-up to observe whether the benefit of disease-free survival will translate into an overall survival benefit
.

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
.
However, the optimal duration of EGFR-TKI adjuvant therapy still needs further analysis
.
In response to this medication problem, another randomized study (NCT01929200) of the adjuvant therapy strategy of icotinib is underway
.

Note: The original text has been deleted

Reference

[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://