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Aleginib adjuvant treatment for ALK-positive NSCLC, disease-free survival rate of 93.8%!
撰文 | Ww
On April 11, 2024, the interim analysis results of the global, phase III, open-label, randomized trial ALINA conducted by the team of Professor Wu Yilong from Guangdong Provincial People's Hospital and Guangdong Institute of Lung Cancer were published in the New England Journal of Medicine. The study investigated the efficacy and safety of adjuvant alectinib compared with traditional adjuvant platinum-based chemotherapy in patients with ALK-positive stage IB, II, or IIIA non-small cell lung cancer (NSCLC) after resection.
Figure 1: Screenshot of the homepage of the study
A few days ago, the Guangdong Provincial People's Hospital held a high-profile press conference. At the meeting, Professor Wu Yilong and Director Zhong Wenzhao discussed in depth the potential impact of the ALINA study results on the strategies of clinicians in the treatment of ALK-positive patients with early-stage NSCLC, how the advantages of alectinib in terms of safety affect the adjuvant therapy of patients, and whether the indication approval and guideline update of alectinib and other drugs can replace alectinib.
Figure 2: Group photo of the press conference (source: CTONG's official WeChat platform)
In this article, we summarize the highlights of the research and the press conference for the benefit of readers.
ALINA Study: 2-year disease-free survival rate of 93.8%!
NSCLC is the most common type of lung cancer, accounting for about 85% of all lung cancer cases. Among them, about 4%-5% of patients carry ALK gene rearrangements, such patients usually have a young age of onset, do not smoke or smoke slightly, and the pathological type is mostly adenocarcinoma, with a high degree of malignancy, and often has large lesions, lymph node metastases, and poor survival prognosis when diagnosed.
In the past, platinum-based chemotherapy was recommended as adjuvant therapy for patients with post-resectomy ALK-positive NSCLC, however, this treatment has been associated with only limited survival improvements, and the risk of disease recurrence remains high. Alectinib is an oral tyrosine kinase inhibitor (TKI) that targets ALK gene rearrangements. In patients with advanced ALK-positive NSCLC, alectinib has demonstrated long progression-free survival (PFS) and high central nervous system (CNS) efficacy. Therefore, the investigators began to explore alectinib as an adjunctive treatment for patients with ALK-positive NSCLC who have completely resected.
From August 2018 to December 2021, a total of 257 patients with ALK-positive stage IB-IIIA NSCLC who underwent complete resection were included in the study, of which 130 patients received 2 years of alectinib and 127 patients received 4 cycles of chemotherapy. The primary endpoint was disease-free survival (DFS) as assessed by the investigator (first tested in patients with stage II-IIIA and then expanded to the overall intention-to-treat population), with other endpoints including CNS-free survival, overall survival, and safety.
The results showed that 14 (12%) in the alectinib group and 45 (39%) in the chemotherapy group had recurrence, metastasis or death among patients with stage II-IIIA. The two-year DFS rate was 93.8 percent in the alectinib arm and 63.0 percent in the chemotherapy arm. The 3-year disease-free recurrence rates were 88.3% and 53.3%, respectively. Compared with chemotherapy, alectinib reduced the risk of recurrence, metastasis or death by 76% (HR=0.24, P<0.001).
In the overall intention-to-treat population, the two-year DFS rate was also significantly higher in the alectinib arm than in the chemotherapy arm (93.6 versus 63.7 percent), compared with the three-year disease recurrence rate of 88.7 and 54.0 percent, respectively. Overall survival data are immature in current trials, but alectinib significantly improved DFS compared with platinum-based chemotherapy in patients with resected stage IB, II, or IIIA-positive ALK-positive NSCLC.
Figure 3. DFS outcomes of alectinib versus chemotherapy
Alectinib reduces the risk of brain metastases, and the safety is controllable!
Notably, alectinib demonstrated significant clinical benefit in metastases-free survival. Only 4 patients treated with alectinib developed brain metastases compared with 14 in the chemotherapy group. Compared to chemotherapy, alectinib reduced the risk of brain metastases or death by 78%. Overall, patients with ALK-positive NSCLC have a high risk of brain metastases, with approximately 50% to 60% of patients developing brain metastases, a finding that is particularly important for patients with ALK-positive NSCLC.
Figure 4. CNS outcomes of alectinib versus chemotherapy
In terms of safety, the safety profile of alectinib was consistent with previous reports, mainly reflected as low-grade adverse events, and no new safety concerns were identified. Although the duration of treatment with alectinib was much longer than that of chemotherapy (median 2 versus 2 months), a similar number of adverse events were observed in both groups, and the proportion of patients who discontinued treatment due to adverse events was lower in the alectinib group (5.5 versus 12.5 percent).
The ALINA study illuminates the therapeutic landscape for patients with ALK-positive NSCLC
Figure 5. Professor Wu Yilong's on-site sharing at the press conference (source: CTONG's official WeChat platform)
Professor Wu Yilong emphasized at the press conference: "No unexpected side effects or unknown complications caused by alectinib have been observed so far. Regarding the impact of long-term use of alectinib on quality of life, the results will be presented at this year's American Society of Clinical Oncology (ASCO) Congress. We look forward to receiving regulatory approvals for the indication at home and abroad and being recommended by more treatment guidelines, thereby providing patients with more treatment options." ”
In addition, Professor Wu Yilong said that in the ALINA study, it must be clear that the drug used is alectinib and cannot be replaced by other drugs. From a scientific point of view, due to the lack of sufficient evidence for long-term use of other drugs, although many drugs may have similar mechanisms of action, their specific manifestations, including side effects and tolerability, need to be evaluated when considering alternatives.
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Editor in charge: Sheep
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