Adjuvant alectinib ‘important new treatment strategy’ for resectable ALK-positive NSCLC

medwireNews: Individuals with resectable, ALK translocation-positive non-small-cell lung cancer (NSCLC) derive a significant disease-free survival (DFS) benefit from adjuvant treatment with alectinib rather than chemotherapy, shows the ALINA study. Presenting the findings at the ESMO Congress 2023 in Madrid, Spain, investigator Benjamin Solomon (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) noted that the DFS improvement was not only statistically significant but also clinically meaningful, and the safety profile was as expected. He therefore believes that “adjuvant alectinib represents an important new treatment strategy for patients with resected, stage IB–IIIA, ALK-positive non-small-cell lung cancer.” Marina Garassino (University of Chicago, Illinois, USA) – who discussed the presentation – said that the DFS results are “impressive,” but she does not think that “we should give up” the use of chemotherapy in ALK-positive patients just yet because “chemotherapy is the regimen that showed an increase in terms of overall survival in the overall population.” ALINA is a phase 3 trial in which 257 early-stage patients were randomly assigned to receive adjuvant alectinib 600 mg twice daily for up to 2 years or four cycles of platinum-based chemotherapy given every 3 weeks. Participants were followed up for a median of 27.9 and 27.8 months, respectively, at which point the primary endpoint of DFS in stage II–IIIA patients (n=231) was significantly longer with alectinib than chemotherapy, with the median unreached and 44.4 months, respectively. This corresponded to a 76% reduction in the risk for recurrence or death with the ALK inhibitor. The 24-month DFS rates in the alectinib and chemotherapy arms were 93.8% and 63.0%, respectively, while the 36-month rates were 88.3% and 53.3%. DFS was similarly significantly prolonged with alectinib in the overall study population comprising patients with stage IB–IIIA disease, with the median once again not reached versus 41.3 months with chemotherapy, and an identical 76% reduction in the risk for recurrence or death. The DFS rates among alectinib- and chemotherapy-treated participants were 93.6% versus 63.7% at 24 months and 88.7% versus 54.0% at 36 months. Solomon pointed out that the overall survival data were not mature at the time of data cutoff, with only six deaths (two in the alectinib arm and four in the chemotherapy arm) thus far. Reporting on the subgroup analyses, he highlighted that “a consistent effect was seen across the stage groups.” The effect was significant for all but the stage IB population, which Solomon said was “likely due to the relatively small number of patients in this group – 26 compared to 92 in the stage II and 139 in the stage IIIA populations.” The incidence of grade 3–4 adverse events (AEs) was comparable between the alectinib and chemotherapy arms, at 30% and 31%, respectively, even though the median duration of treatment with alectinib was considerably longer, at 23.9 months versus 2.1 months with chemotherapy. There were no grade 5 AEs in either arm. “The most frequently observed adverse events with alectinib treatment were typically low-grade elevations of creatinine kinase or liver function tests as well as constipation and myalgia, consistent with the known safety profile of alectinib,” reported Solomon. A greater proportion of alectinib-treated patients than their counterparts given chemotherapy required a dose reduction (26 vs 10%) or dose interruption (27 vs 18%) due to AEs, but a smaller proportion discontinued treatment (5 vs 13%). The discussant pointed out that the toxicity in the adjuvant setting “could be an issue,” with “patients that are [already] potentially cured by surgery having to take eight capsules a day for a couple of years,” compared with chemotherapy for just 4 months. Nevertheless, Garassino said she will discuss the option of alectinib with her patients but make them aware of the toxicity profile and the lack of “a clear overall survival benefit” at this point. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group ESMO Congress 2023; Madrid, Spain: 20–24 October

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