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The latest data from the ALINA study was unveiled at the 2024 AATS
In October 2023, at the annual meeting of the European Society for Medical Oncology (ESMO), the ALINA study data was presented in an oral presentation at the Presidium Symposium [1]. The results showed that compared with platinum-containing chemotherapy (mDFS 44.4 months), adjuvant alectinib (mDFS not reached) brought a significant disease-free survival (DFS) benefit to patients (HR 0.24; 95% CI: 0.13~0.45), and reduced the risk of disease recurrence or death in patients with ALK-positive early-stage NSCLC by 76%. With its unprecedented excellent results, alectinib has opened up a new idea of targeted adjuvant therapy for patients after NSCLC surgery.
On April 27, 2024, the 104th Annual Meeting of the American Academy of Thoracic Surgery (AATS) was held as scheduled. Professor Wu Yilong from Guangdong Provincial People's Hospital brought the latest data of the ALINA study to the international stage again! This study data analyzed the clinical benefits of alectinib in postoperative adjuvant therapy under different disease characteristics, including different lymph node stages. Professor Yang Fan from Peking University People's Hospital was invited to share the latest data of ALINA research and its important clinical value.
Expert Profile
Professor Yang Fan
Vice President of Peking University People's Hospital
Peking University People's Hospital, Chief Physician, Professor, Doctoral Supervisor
Member of AATS of the American Society for Thoracic and Cardiovascular Surgery
Chairman of the Thoracic Surgery Branch of the Chinese Association of Research Hospitals
Member of the Standing Committee of the CSCO Non-Small Cell Professional Committee of the Chinese Society of Clinical Oncology
Member of the Standing Committee of the Chinese Society of Clinical Oncology CSCO Geriatric Tumor Committee
Member of the Standing Committee of the CSCO Youth Committee of the Chinese Society of Clinical Oncology
Member of the Standing Committee of CACA Lung Cancer Professional Committee of Chinese Anti-Cancer Association
Vice Chairman of the Lung Cancer Youth Committee of Beijing Medical Award Foundation
Member of the Standing Committee of the Lung Cancer Committee of the Beijing Oncology Society
Lung Cancer 副主编
Frontiers in Oncology副主编
ALINA data were updated and consistent benefits were observed across populations with different disease characteristics
Objectives: The ALINA study (NCT03456076) is a phase III, randomized, open-label study to evaluate the efficacy and safety of alectinib or adjuvant chemotherapy in patients with ALK-positive NSCLC after complete resection (≥4 cm)–stage IIIA (UICC/AJCC version 7). The primary endpoint is investigator-assessed DFS. Secondary/exploratory endpoints included: time to central nervous system recurrence or death, and safety.
Fig.1 Study design
The surgical characteristics of the enrolled patients were analyzed, and the baseline patients between the experimental group and the control group were balanced, and the proportion of patients with lymph node N2 in the experimental group and the control group was 49% and 52%, respectively.
Fig.2 Characteristics of the two groups of patients
The DFS benefit was observed in patients with stage II and stage IIIA patients, with HR of 0.28 (95% CI: 0.11, 0.70) and 0.22 (95% CI: 0.10, 0.51), respectively. Compared with the main results of the AJCC 7th edition staging analysis, the DFS of patients with stage IB (≥4 cm) to IIIA was 0.24 (95% CI: 0.13, 0.43), and the trend was consistent and comparable.
Fig. 3 DFS benefit for patients with stage II–IIIA (UICC/AJCC v8).
The latest results from the ALINA study also analyze the benefits for patients with different lymph node stages. The benefit of DFS was observed in patients with exploratory analysis of lymph node N0, N1, and N2, with HR values of 0.19 (95% CI: 0.04, 0.88), 0.34 (95% CI: 0.13, 0.89), and 0.21 (95% CI: 0.09, 0.47), respectively. Among them, for patients with a high risk of recurrence such as N2, the 3-year DFS rate of adjuvant alectinib can reach 92.6%, compared with 47.5% in the chemotherapy group, an increase of 45.1%.
Fig.4 DFS benefit for patients with different lymph node stages
In addition to exploratory analyses of different surgical stages and lymph node status, DFS benefits from adjuvant alectinib were consistently observed in other subgroups presented in this study, including tumor size, tumor assessment, and postoperative medication intervals.
Fig. 5 DFS benefit of patients in each subgroup analysis
In terms of safety, as of the data cut-off (June 26, 2023), the median duration of treatment was 23.9 months for alectinib and 2.1 months for the chemotherapy group. The proportion of patients who discontinued treatment due to AEs was 5% in the alectinib group, compared with 13% in the chemotherapy group. No grade 5 adverse events were detected during the whole follow-up process, and no new safety signals were observed.
Fig.6 Safety data of the ALINA study (incidence of AEs ≥15%)
Regardless of the patient's condition, alectinib has been "consistent" to deliver significant DFS benefits
It is well known that lung cancer is the malignant tumor with the highest number of cancer-related deaths worldwide. Among the factors affecting the ultimate survival benefit of patients, the factor of lymph node metastasis cannot be ignored. Lymph node metastasis has been shown to directly affect OS, DFS, recurrence-free survival (RFS), and recurrence rates, and most of the results suggest that lymph node metastasis is one of the independent risk factors for poor prognosis [2].
In the results of the surgical characteristics analysis of patients in the ALINA study, it can be seen that patients enrolled in patients with various lymph node stages of N0, N1, and N2 have significant and consistent DFS benefits from treatment with alectinib. In particular, for patients with a high risk of postoperative recurrence in the N2 group, the DFS HR in the alectinib treatment group was 0.21 (95% CI: 0.09, 0.47), reducing the risk of death and recurrence by 79%, which is of great reference value for surgical practice. All in all, alectinib is undoubtedly the preferred strategy for adjuvant therapy for patients with NSCLC after ALK-positive surgery, regardless of N stage.
At the same time, there are differences between the criteria used in the recruitment of the ALINA study (UICC/AJCC 7th edition) and the current clinical use (UICC/AJCC 8th edition), and the treatment benefit of patients under different clinical stage criteria is also worthy of attention. Therefore, the updated data of this conference explored the efficacy of adjuvant alectinib after the UICC/AJCC version 8 staging, so that clinicians can have a deeper understanding of the beneficiaries of adjuvant alectinib. The results suggest that adjuvant alectinib postoperative therapy can bring consistent DFS benefits to patients with different stages, regardless of the staging criteria. This undoubtedly provides better evidence support for further guidance on the adjuvant treatment of NSCLC patients after clinical ALK-positive surgery.
The data from the ALINA study were also analyzed in subgroups according to the clinical staging criteria of the enrolled patients, tumor diameter, surgical lymph node dissection protocol, and time from surgery to adjuvant therapy. Alectinib has shown a trend of DFS benefit.
Efficacy & Safety, the use of alectinib kills two birds with one stone
Safety has always been an important guarantee for cancer patients to receive long-term treatment and ultimately achieve survival benefits. Overall, patients with early-stage lung cancer have a better prognosis than patients with advanced stage, so there are higher requirements for drug safety, quality of life and ease of taking drugs. Based on late experience, alectinib has demonstrated good safety outcomes in a series of ALEX, J-ALEX, and ALESIA studies, and in the safety data of the ALINA study, it can also be seen that alectinib has consistently good safety profile.
The guidelines recommended and approved by the FDA, and we look forward to benefiting more patients
The incidence of ALK fusions in NSCLC is low, only about 5%, and ALK fusion mutations are also called "diamond mutations" because of the good efficacy of targeted therapy in such patients. With the continuous advancement and optimization of the treatment mode, targeted therapy has gradually entered the perioperative period from the late stage, and the trial and layout are carried out. Based on the impressive results of the ALINA study, the FDA finally approved alectinib on April 18, 2024 for the postoperative adjuvant treatment of adult patients with ALK-positive non-small cell lung cancer (tumor size ≥4 cm or node-positive). On April 23, 2024, the V5 version of the NCCN guidelines was updated to add a recommendation for the postoperative adjuvant therapy of alectinib in patients with stage II-IIIA, IIIB (T3, N2) NSCLC and ALK rearrangement positive (Class 1 recommendation). At the same time, at the CSCO guideline meeting on April 27, alectinib was also added as a recommendation for the postoperative adjuvant treatment of ALK+ NSCLC patients (grade II). This makes us look forward to the early approval of the indication of adjuvant alectinib in China. At the same time, we also look forward to the release of the results of studies on the adjuvant treatment of OS with alectinib after further follow-up observations, so as to provide more valuable reference for future clinical trials.
Exciting information is waiting for you
Bibliography:
[1] Wu YL, Dziadziuszko R, Ahn JS, et al. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024; 390(14):1265-1276. doi:10.1056/NEJMoa2310532
[2] Yi-Long Wu,Benjamin Solomon, Jin Seok Ahn,etal. Disease characteristics and treatment outcomes in patients with resected early-stage ALK+ non-small cell lung cancer from ALINA, a phase III randomized trial of adjuvant alectinib vs. chemotherapy
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