Patients with ALK-positive, early-stage non-small cell lung cancer obtained significant improvement in disease-free survival.
Patients with resected ALK-positive non-small cell lung cancer (NSCLC) experienced a significant improvement in disease-free survival when treated with Alecensa (alectinib), an oral ALK inhibitor, according to recent trial results.
Findings from the phase 3 ALINA trial, which were presented at the 2023 ESMO conference, showed that the targeted therapy elicited superior outcomes than platinum-based chemotherapy across all prespecified subgroups.
Key Findings
The median follow up was 27.9 months with Alecensa and 27.8 months with chemotherapy.
Patients with stage 2 to 3A disease who received Alecensa (116 patients) had a 76% reduced risk of disease recurrence or death compared with those who received platinum-based chemotherapy (115 patients). Among these two groups, the median DFS (the time after treatment ends when a patient with cancer has no signs or symptoms of cancer) was not reached with Alecensa versus 44.4 months with chemotherapy.
Further, the two-year DFS rates were 93.8% versus 63%, respectively. The three-year DFS rates were 88.3% versus 53.3%.
In the intention-to-treat population, which included the entire study population with stage 1B-3A disease, the median DFS was not reached among patients who received Alecensa (130 patients) versus 41.3 months among those who received chemotherapy (127 patients).
Also in the intention-to-treat population, the rates of two-year DFS were 93.6% versus 63.7% and the three-year DFS rates were 88.7% versus 54%, respectively.
Of note, the rate of severe or life-threatening side effects was similar between the two groups: 30% and 31% of patients receiving targeted or chemotherapy, respectively, reported high-grade side effects. No deaths from side effects were reported in either cohort.
“Treatment with adjuvant (Alecensa) resulted in a statistically significant and clinically meaningful improvement in DFS compared with chemotherapy,” Dr. Ben Solomon, a Medical Oncologist at the Peter MacCallum Cancer Centre in Australia, said in a presentation of the data.
“The DFS benefit was seen consistently across subgroups and an (improvement) in (central nervous system)-DFS was observed,” Solomon said.
Significance
Among patients with NSCLC, approximately 4% to 5% will harbor an ALK rearrangement. These patients tend to be 55 years or younger, to not have a history of smoking, and to be at a higher risk of brain metastases — nearly half of patients with ALK alterations develop brain metastases.
Approximately 30% to 40% of patients with NSCLC will receive a diagnosis of resectable disease. Unfortunately, nearly half of patients with early-stage disease will experience disease recurrence after surgery, highlighting the importance of effective adjuvant options in this space.
The standard treatment approach following surgery is currently platinum-based chemotherapy for patients with stage 2B to 3A, ALK-positive disease; however, this modality is associated with modest improvements in survival outcomes. Similarly, immunotherapy approaches have not been fruitful for patients with resected, ALK-positive disease.
Alecensa already plays a role for certain patients with ALK-positive NSCLC. For patients with advanced disease who have not yet undergone resection, Alecensa is the preferred front-line regimen. Three distinct phase 3 trials have demonstrated significant progression-free survival benefits and intracranial control with Alecensa versus crizotinib in this setting. It is also associated with a high rate of intracranial activity. As of August 2023, it is estimated that more than 92,000 patients with ALK-positive disease have been treated with the oral TKI.
The current findings are the first to compare this agent against platinum-based chemotherapy in a population of ALK-positive patients in the adjuvant setting.
Secondary Outcomes
“In terms of the subgroup analysis, benefit in favor of (Alecensa) was seen across all the pre-defined subgroups evaluated, including stage and nodal status,” Solomon emphasized in the presentation.
When looking at DFS by stage, the two-year results continued to favor Alecensa. For those with stage 1B disease (26 patients), stage 2 (92 patients) and stage 3A (139 patients) disease, respectively, the rates of DFS after 2 years were 92.3%, 95.6%, and 92.7% with Alecensa versus 71.6%, 66.3%, and 60.7%, respectively.
Therefore, the reduced risk of death or recurrence was 79% with stage 1B, 76% with stage 2 and 75% with 3A disease, respectively.
In addition, four patients receiving Alecensa versus 14 patients receiving chemotherapy in the intention-to-treat population experienced brain recurrence. The rate of central nervous system DFS at two years was 98.4% versus 85.8%, respectively. At three years, the rates were 95.5% versus 79.7%.
Regarding the agent’s safety summary, the median duration of treatment was 23.9 months with Alecensa and 2.1 months with chemotherapy, leading to a longer safety follow-up time with the targeted treatment. The rate of any-grade side effects was 98% versus 93%, respectively. Of note, a higher percentage of patients receiving Alecensa needed to dose reduce because of a side effect (26% versus 10%) or interrupt treatment because of a side effect (27% versus 18%), although fewer needed to discontinue treatment overall (5% versus 13%).
The most common side effects reported with Alecensa were increased in blood creatine phosphokinase (indicating injury or stress to muscle tissue, the brain or the heart), constipation, and increases in aspartate aminotransferase and alanine aminotransferase (both of which indicate liver disease), as well as an increased in blood bilirubin (which may indicate liver dysfunction). In the chemotherapy arm, the most common side effects were nausea, constipation, anemia and decreased appetite.
“Adjuvant (Alecensa) was tolerable and in line with the known safety profile of (Alecensa),” Solomon concluded. “Adjuvant (Alecensa) represents an important new treatment strategy for patients with resected, stage 1B-3A, ALK-positive, NSCLC.”
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