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Abstract
BackgroundWhereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC.MethodsWe included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases.ResultsA total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%).ConclusionOur analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.
Highlights
Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death globally in 2020, with a 5-year survival rate of only 10 to 20% [1], and non-small cell lung cancer (NSCLC) accounts for about 85% of overall reported cases [2]
Multiple generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) have been developed (including crizotinib; alectinib, ceritinib, brigatinib, and ensartinib; and lorlatinib), and most of these TKIs have been established as standard first line treatments [6, 7]
Patients harboring an ALK -rearrangements are prone to central nervous system (CNS) metastasis, the ideal treatment could differ in patients stratified by CNS metastasis [9]
Summary
Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death globally in 2020, with a 5-year survival rate of only 10 to 20% [1], and non-small cell lung cancer (NSCLC) accounts for about 85% of overall reported cases [2]. Several randomised controlled trials (RCTs) using only the direct comparison model have been conducted for conclusive evidence about the comparative efficacy and safety of first line treatments for patients with advanced ALK-rearranged NSCLC [10,11,12,13,14]. They have been unable to address the aforementioned problems, especially the second and third-generation TKIs. To provide additional evidence to guide treatment choices for ALK -rearranged NSCLC patients, we conducted a Bayesian network meta-analysis to comprehensively integrate all available direct and indirect evidence with a well-designed and comparative synthesis. Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant.
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