The use of alectinib to treat ALK-positive non–small cell lung cancer resulted in better overall survival compared with ceritinib.
A longer overall survival (OS) was achieved in patients with ALK-positive non–small cell lung cancer who were treated with alectinib (Alecensa) compared with ceritinib (Zykadia), according to results from a study published in JAMA Network Open.
When comparing with ceritinib real-world data, patients who were given alectinib had a longer OS in clinical trials (adjusted hazard ratio [HR], 0.59; 95% Ci, 0.44-0.75; P <.001) and in real-world findings (HR, 0.46; 95% CI, 0.29-0.63; P<.001). In terms of the worst-case HR estimate of 0.59 (95% CI, 0.44-0.75), a residual confounding by hypothetical confounder that investigators deemed to be associated with mortality and treatment with a risk-ratio of more than 2.24 was needed in order to reverse any findings.
A total of 355 patients were enrolled in the trial, 183 of whom were included in the alectinib trial, 91 in the ceritinib real-world data group, and 81 in the alectinib real-world data group. Central nervous system metastases were found in the 61.2% of patients in the alectinib trials compared with 20.9% of those in the ceritinib real-world data group. Patients in the alectinib real-world data group had a mean age of 58.69 years and were more likely to have a favorable ECOG performance status of 0 or 1 (92.4%), to be White (72.7%), and to be smokers (44.4%). Comparatively, 77.1% of those in the ceritinib real-world data group had an ECOG performance status of 0 or 1, 62.4% were White, and 32.9% were smokers.
A total of 34.6% of patients were missing ECOG performance statuses in the alectinib real-world data group. Other missing variables from the 2 real-world data groups were race in 6.6% of patients in the ceritinib group and 4.9% in the alectinib group, and cancer stage at diagnosis in 1 patient in the ceritinib group.
The adjusted HR for mortality in the alectinib trial compared with ceritinib real-world data was 0.55 (95% CI, 0.31-0.95; P= .03). When comparing the OS for alectinib real-world data compared with ceritinib real-world data, investigators reported an HR of 0.47 (95% CI, 0.23-0.96; P = .04). The median survival time for patients taking alectinib was 29.1 months (95% CI, 21.1–not estimable [NE]) compared with 14.9 months among those taking ceritinib (95% CI, 9.1-35.0).
The alectinib real-world data group had a significantly lower risk of all cause death compared with the ceritinib real-world data group (HR, 0.46; 95% CI, 0.29-0.63; P <.001). The alectinib real-world data group also had a longer median survival time of 42.6 months (95% CI, 24.4-NE) versus the ceritinib real-world data group at 17.8 months (95% CI, 11.2-26.5).
When investigators adjusted for 11 baseline covariates including comorbidities, metastases, insurance status, and an Asian category for race, they identified an HR of 0.60 (95% CI, 0.38-0.82). However, the OS for the alectinib trial and alectinib real-world data groups was not significantly different (HR, 1.19; 95% CI, 0.83-1.56).
Investigators hypothesized that the distribution of comorbidities and metastases may have differed between trial data and real-world data because of the differences in surveillance and recording between trial and real-world data. The sensitivity analysis showed a 40% greater prevalence among those without a recorded CNS metastasis or comorbidity than reported in the ceritinib real-world data group.
Wilkinson S, Gupta A, Scheuer N, et al. Assessment of alectinib vs ceritinib in ALK-positive non-small cell lung cancer in phase 2 trials and in real-world data. JAMA Netw Open. 2021;4(10):e2126306. doi:10.1001/jamanetworkopen.2021.26306