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18-01-2019 | Non-small-cell lung cancer | News | Article

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Prolonged OS possible for ALK-positive stage IV NSCLC

medwireNews: Individuals with stage IV non-small-cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) translocations can hope to achieve overall survival (OS) of nearly 7 years, suggests a US cohort analysis.

As reported in the Journal of Thoracic Oncology, median OS from the diagnosis of stage IV disease was 6.8 years among 110 patients treated with an ALK inhibitor between 2009 and 2017.

Researcher Jose Pacheco (University of Colorado Anschutz Cancer Center, Aurora, USA) and co-workers note that 45% of the patients in the cohort were still alive at data cutoff – at a median follow-up of 47 months – and therefore they believe that the median OS “may increase further” with longer follow-up.

Additionally, the 4- and 5-year OS rates were 73% and 60%, respectively, which the team says compare favorably with previously reported corresponding rates of 57% and 36% in ALK-positive patients using crizotinib.

The median age of the cohort was 53 years, and it comprised an equal proportion of men and women. The majority of patients were never smokers (82.7%), Caucasian (80.0%), and had received crizotinib as the first ALK inhibitor (95.5%). Thirty percent of participants had central nervous system (CNS) metastases at the time of diagnosis of stage IV NSCLC.

Speaking to medwireNews, Pacheco explained that the reasons for the observed improvement in OS could be manifold. He noted, for instance, that “a much higher” proportion (78%) of the current cohort received next-generation ALK inhibitors at any timepoint after crizotinib compared with previous studies, and a large proportion (48%) received treatment for oligoprogressive disease while remaining on crizotinib.

Pacheco added that “the next generation ALK inhibitors we used more commonly immediately post-crizotinib were the highly CNS penetrant next-generation ALK inhibitors alectinib and brigatinib,” and many of the patients were enrolled in clinical trials.

Interestingly, a quarter of the 48 patients who were diagnosed in 2010 or earlier remained alive for at least 8 years from the development of stage IV disease, and 83% of these so-called “very-long term survivors” were alive at data analysis.

“The proportion of [very long-term] survivors will likely increase with greater incorporation of next-generation ALK inhibitors as initial systemic therapy for patients with stage IV disease, emphasizing the importance of long-term tolerability of any therapeutic approaches,” write the researchers.

Furthermore, Pacheco said: “To improve survival further it will be important to develop new medications or combinations of medications that in addition to targeting ALK resistance mutations well, also target non-ALK dependent mechanisms of resistance better than the currently available treatments.

“We are attempting to do this by gaining more information on non-ALK dependent mechanisms of resistance through on-treatment biopsies and neoadjuvant therapy studies, as well as now currently ongoing early phase clinical trials,” he concluded.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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