100% Chinese population, better efficacy: ADAURA China subgroup analysis unveiled at 2022 ELCC

Introduction In the ADAURA global clinical study, adjuvant osimertinib in the treatment of stage II-IIIA EGFR mutation-positive NSCLC brought an overwhelming DFS benefit, reducing the risk by 83% (HR 0.
17) and significantly reducing local recurrence (recurrence rate 7%).
vs.
18%) and distant recurrence (4% vs.
28%), and in particular significantly reduced the risk of central nervous system (CNS) progression (ie, brain recurrence) or death by 82%
.

Osimertinib has changed the clinical practice of early and mid-stage adjuvant with the data of ADAURA study.
In April 2021, osimertinib became the first targeted drug approved in China for postoperative adjuvant treatment of patients with stage IB-IIIA EGFR-mutant NSCLC
.

And the program has been included in the unanimous recommendation of the Chinese Medical Association, the Chinese Anti-Cancer Association, the American NCCN, ASCO, ESMO and other major guidelines at home and abroad
.

The Chinese subgroup analysis data of this study have been released at the 2022 European Lung Cancer Congress (ELCC)
.

The curative effect is better, and the data is even more amazing; it fills the blank of adjuvant treatment data for Chinese stage IB patients.
A total of 159 Chinese patients were included in the Chinese subgroup analysis.
The study design is shown in Figure 1
.

Figure 1: ADAURA's study design The primary end point of the study is the investigator-assessed DFS (disease-free survival) of patients with stage II-IIIA stages.
From the published data, it can be seen that the results of this study have a clear trend of benefit (Figure 2), and the data are more Amazing, DFS HR 0.
16 (95%CI 0.
08-0.
31)
.

This means that patients with stage II-IIIA adjuvant osimertinib had an 84% reduction in the risk of disease recurrence or death (DFS HR=0.
17 in the global population, reducing the risk of disease recurrence or death by 83%) [median DFS : not reached (NR) in the osimertinib arm vs 18.
3 months in the placebo arm]; Figure 2: Primary endpoint: DFS in patients with II-IIIA NSCLC A secondary endpoint was DFS in patients with stage IB-IIIA Shows a clear trend of benefit (Figure 3) and the data are equally impressive, DFS HR 0.
18 (95%CI 0.
10-0.
33) (DFS HR=0.
20 in the global population, reducing the risk of disease recurrence or death by 80%) [median DFS: not reached (NR) in the osimertinib group vs 24.
9 months in the placebo group]; Figure 3: Secondary endpoint: DFS in patients with IB-IIIA NSCLC A larger IB population (43% vs 32%) was included (Table 1), which is also closer to the current clinical reality in China
.

Compared with other first- or second-generation EGFR-TKI adjuvant therapy studies, such as ADJUVANT, EVIDENCE, etc.
, which were not included in stage IB, the results of the Chinese subgroup are undoubtedly of great significance, which fills the clinical evidence gap of adjuvant targeted therapy for Chinese stage IB patients
.

For stage IB patients in China, this is also the first high-quality evidence that adjuvant targeted therapy has a significant benefit
.

Table 1: Comparison of baseline characteristics of the ADAURA Chinese cohort and the global population In addition to the above, the study also reported DFS benefit results for each prespecified subgroup: trends in DFS benefit were observed
.

Among them, 67% of Chinese patients received adjuvant chemotherapy, which is also in line with Chinese guidelines for the treatment of stage II/III NSCLC
.

The significant benefit of this part of the population is HR 0.
13 (95%CI 0.
05-0.
31), which also means that sequential osimertinib after adjuvant chemotherapy can significantly reduce the risk of disease recurrence or death by 87%, which is really shocking! Up to now, there is no sequential evidence after adjuvant chemotherapy for the previous generation of EGFR-TKIs, and osimertinib also fills the evidence gap for adjuvant targeted therapy in this part of the Chinese population
.

Figure 4: A clear trend in DFS benefit was observed in all prespecified subgroups
.

 The reliability of the data is higher, and the research conclusions are more reliable.
The maturity of the research data is complementary to the reliability of the data results
.

We saw an overall maturity of 40% for the primary endpoint of the Chinese cohort study, which provides greater confidence in the trend of the results
.

But we also see that under the premise of high maturity, the data maturity of the osimertinib group and the control group are 10% and 65%, respectively, and the difference between the two is huge; this also confirms the outstanding performance of osimertinib.
Efficacy, compared with the control group, more patients in the osimertinib group were still in a disease-free state
.

At the same time, we also looked at another auxiliary targeting study EVIDENCE.
According to the number of events in the PP population released by it, the maturity of the results of this study is expected to be about 26%.
It can be seen that for the Chinese population, the evidence of ADAURA model Credibility will be more powerful
.

 In terms of safety, although the median drug exposure time of osimertinib in the Chinese subgroup was 26.
1 months, which was 3.
6 months longer than that in the global cohort (22.
5 months), the overall safety was still consistent with the global population (see Table 2).

.

 Table 2: Chinese cohort and global cohort safety summary 100% Chinese population reviewed the ADAURA study.
According to the registered clinical research participating institutions inquired on the Medical Cube website, there are 30 sub-centers in China, as follows (ranking by website) : The above centers basically include representative hospitals in the north and south of China, covering a wide range of areas, and the enrolled groups are also very representative
.

 Conclusion: The ADAURA Chinese subgroup showed better efficacy data, and also provided sufficient evidence for Chinese stage IB patients and the population who used osimertinib sequentially after adjuvant chemotherapy
.

Of course, the higher data credibility of the study also guarantees the reliability of the efficacy evidence
.

Moreover, the study is based on 30 sub-centers and 100% Chinese population, and the results have higher reference value and significance for Chinese patients
.

The third-generation EGFR-TKI osimertinib may really be a gift to the Chinese, and the key to cure for Chinese patients with early and mid-stage non-small cell lung cancer
.

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Clin Cancer Res 2022 Jan 10:clincanres *This article is copyrighted All the original author, if you need to reprint, please contact the original author for authorization