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Patients with advanced, ALK-positive non-small cell lung cancer are living longer
Targeted treatments and pemetrexed-based chemotherapies appeared to be among factors associated with prolonged OS in patients with stage 4, ALK-positive non-small cell lung cancer, according to results of a retrospective study published in Journal of Thoracic Oncology.
Two decades ago, patients with stage 4 NSCLC had a 2% chance of achieving 5-year OS, according to NCI data. In the current study — which included 110 patients with ALK-positive disease treated with an ALK inhibitor at University of Colorado Cancer Center between 2009-2017 — up to 50% of patients survived 6.8 years after diagnosis.
“What this shows is that with the development of good targeted therapies for ALK-positive lung cancer, even patients with stage 4 disease can do well for many, many years,” Jose M. Pacheco, MD, oncologist and investigator at University of Colorado Cancer Center, said in a press release.
Of the 110 patients (median age, 53 years; 50% women; 80% white; 83% never-smokers) in the retrospective analysis, 88 presented with stage 4 disease, whereas the other 22 developed stage 4 disease from an earlier stage.
About 30% (n = 33) of the patients had brain metastasis at stage 4 diagnosis, and five patients had metastatic disease limited to the brain.
Patients had a median of three (range, 1-6) organs with metastasis at the time of stage 4 diagnosis.
Almost all the patients (n = 105) received crizotinib (Xalkori; Pfizer, EMD Serono) as their first ALK inhibitor. The other five patients were treated with a next-generation ALK inhibitor as a first-line therapy, resulting in insufficient data to compare OS with patients who received crizotinib.
OS served as the study’s primary endpoint.
Results showed median OS from the time of stage 4 diagnosis of 81 months (range, 3-125+).
Researchers observed no significant difference in median OS between the 40 patients who received crizotinib first (86 months) and the 65 patients who received non-ALK inhibitor systemic therapy before crizotinib (79 months).
Among the 102 patients who experienced progression on crizotinib, 83.3% went on to another systemic therapy, 78.4% used another ALK inhibitor, 2% had missing data and 14.7% received no additional systemic therapy. Nine of these patients (9%) received retreatment with crizotinib.
Multivariate analysis revealed brain metastasis at diagnosis of stage 4 disease and year of stage 4 presentation did not significantly affect OS.
However, a greater number of organs with a tumor at stage 4 diagnosis appeared associated with worse OS (HR for each additional organ with a tumor, including central nervous system = 1.49; 95% CI, 1.16-1.91), as did male sex (HR = 2.38; 95% CI, 1.14-4.96).
“A lot of new ALK inhibitors that were developed after crizotinib get into the brain very well, and they work similarly in the brain when compared to outside the brain,” Pacheco said in the press release. “And we’re doing more careful surveillance of patients to see when they develop brain [metastases] ... instead of waiting for symptoms and then treating, we’re monitoring for the development of metastases with imaging of the brain, and if we see something new, we sometimes treat it before it causes symptoms.”
The study’s retrospective nature served as a limitation.
“At this point, 6.8 years is one of the longest median survivals ever reported for a NSCLC subpopulation with stage 4 disease,” Pacheco said. “It shows the benefit of targeted therapy and how it’s changing survival for a lot of patients. And I think it suggests that for some types of NSCLC, it may become much more of a chronic condition rather than a terminal disease.” – by John DeRosier
Disclosures: Pacheco reports consultant fees from AstraZeneca and Novartis, honorarium from Takeda and research funding from Pfizer. Please see the study for all other authors relevant financial disclosures.