Progression-Free Survival Associated With Alectinib vs Crizotinib Among Patients With Advanced NSCLC

For patients with non–small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs), anaplastic lymphoma kinase (ALK) fusion is an indicator of prognosis. However, little real-world data is available on the use of TKIs in patients whose NSCLC yields a positive test result for ALK fusion. 

To determine the survival benefits of crizotinib vs alectinib in these patients, researchers in China conducted a retrospective review of data on 168 patients with ALK-positive locally advanced or metastatic NSCLC (Ca Med. 2022; Published online May 26. doi:10.1002/ cam4.4834). 

“Our results revealed alectinib had better PFS [progression-free survival] and higher intracranial efficacy compared to crizotinib in ALK-positive NSCLC and might improve PFS by comparison with ceritinib and brigatinib after crizotinib failure,” wrote Yurong Wang, MD, Department of Medical Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, and colleagues.

Dr Wang and the research team determined ALK status by using immunohistochemistry or next-generation sequencing (NGS). The study group included 109 patients who received crizotinib and 59 who received alectinib. Patients were enrolled in the study between March 2017 and September 2020. 

The researchers comprehensively analyzed and compared clinical outcomes between TKIs, ALK fusions, EML4-ALK variants, and next-generation TKIs after crizotinib treatment failed. “Echinoderm microtubule-associated protein-like 4 (EML4) is the most common partner of ALK fusion…. And previous studies demonstrated that differential ALK fusions and EML4-ALK variants had differential responses to TKIs,” Dr Wang and colleagues explained.

Results of this analysis showed that, when compared with crizotinib, alectinib resulted in consistently superior PFS (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.24 to 0.77, P=.004). Alectinib was also superior to crizotinib in prolonging intracranial PFS (HR, 0.12; 95% CI, 0.03 to 0.49; P=.003).

In addition, after alectinib treatment, patients in the EML4 group had a better prognosis than those in the non-EML4 group (HR, 0.13; 95% CI, 0.03 to 0.60; P=.009).

However, multivariate Cox regression analysis showed that administering chemotherapy before TKIs or synchronous chemotherapy did not yield additional improvement in PFS over that provided by ALK TKIs alone (P>.05).

Dr Wang and team also found that TP53 co-mutations were relatively common, affecting 16 of the 47 patients tested for these co-mutations with NGS, or 34%. Moreover, patients with these co-mutations had poorer survival than patients without them (adjusted HR, 2.22; 95% CI, 1.00 to 4.92; P=.049).

After crizotinib treatment failed, 33 patients were sequentially treated with the next-generation ALK TKIs ceritinib and brigatinib. After analyzing the outcomes of this salvage treatment, the researchers concluded that alectinib resulted in better PFS than ceritinib and brigatinib (P=.043). 

“This may be partly attributed to the less BBB [blood–brain barrier] penetration of ceritinib than alectinib,” Dr. Wang and team wrote. “In addition, dose reduction or interruption caused by the higher gastrointestinal toxicity of ceritinib [may have] compromised the intracranial protectivity. Our results provide evidence for comparing the efficacy of ceritinib, brigatinib, and alectinib,” they concluded.