Targeted therapies are increasingly common for the treatment of non-small cell lung cancer (NSCLC) containing driver mutations and have led to dramatic improvements in survival outcomes. In particular, ALK inhibitors,of which there are now 4 types approved by the US Food and Drug Administration (FDA), have been associated with median overall survival (OS) times of about 7 years in patients with ALK-positive stage IV NSCLC, compared with 4 months among these patients before these drugs were available.1
Recent research retrospectively analyzed clinical outcomes for 110 patients with ALK-positive stage IV NSCLC who were treated at the University of Colorado Cancer Center in Aurora between 2009 and 2017 to identify clinical variables that are associated with median overall survival (OS).2 The cohort was predominantly Caucasian (80%) and evenly split between men and women. More than 80% of patients had never smoked and 33 patients had brain metastasis at the time of diagnosis with stage IV disease.
The study found that patients who had a greater number of organs with metastases and male patients had worse median OS, whereas those who received pemetrexed-based chemotherapy, either before or after crizotinib, had longer median OS. Importantly, the presence of brain metastasis at the time of stage IV diagnosis was not associated with worse median OS.
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Nearly all (105) of the patients in the cohort received crizotinib, which was the first FDA-approved ALK inhibitor in 2011, and of the 102 patients who progressed on crizotinib, 78.4% received a second ALK inhibitor. In line with previous research, the researchers found a median OS of 81 months from the time of diagnosis with stage IV disease, and 86 months among the patients who received a second ALK inhibitor. A comparison group of 963 patients with stage IV NSCLC of any type who were treated at the center during the same period of time had a median OS of about 9 months.
“This study illustrates very well how getting the appropriate targeted therapy if you have a specific gene alteration for which there is a targeted therapy can really influence long-term survival in a positive way,” Jose M. Pacheco, MD, of the University of Colorado Cancer Center, told Cancer Therapy Advisor.
“This study is also good news for patients who look on the internet and see numbers that are quite different than what we report, because [some cancer] websites … don’t report survival by type of genetic abnormality,” explained Dr Pacheco, lead author of the study, which was published in the Journal of Thoracic Oncology. “You may have a type of lung cancer with a much better prognosis and you can live quite a while.”
“As we improve on treatments for these patients, median OS will likely increase, as we use alectinib and brigatinib, not crizotinib, as the first-line ALK inhibitor,” Dr Pacheco added. Alectinib and brigatinib are second-generation ALK inhibitors that were FDA-approved in 2015 and 2017, respectively, and have been demonstrated to have greater efficacy than crizotinib.3
A 2017 retrospective study of patients in France with ALK-positive, predominantly advanced NSCLC reported a median OS consistent with Dr Pacheco’s research: 89.6 months among patients who received crizotinib followed by alectinib and/or ceritinib from the time of metastatic disease diagnosis.4 A 2015 retrospective study of patients with advanced ALK-positive NSCLC treated with crizotinib followed by ceritinib at 4 institutions in the United States, Europe, Asia, and Australia reported a median OS of 49.4 months from the time of metastatic disease diagnosis.5 Dr Pacheco speculates that the lower median OS in this study may be due to the fact that ceritinib is a less potent ALK inhibitor than alectinib.
