NSCLC treatment failure increases with genomic aberration, never-smokers, non-resection
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Tyrosine kinase inhibitor-sensitive genomic aberrations, unresected tumors and not smoking were associated with increased treatment failure in non-small cell lung cancer, according to a presentation at the virtual ASCO annual meeting.
“The aims of this study were to determine the rate of TKI-sensitive aberrations, the impact of these TKI-sensitive aberrations on treatment failure and the efficacy of post-operative systemic treatments,” Nicolas Zhou, DO, research fellow at The University of Texas MD Anderson Cancer Center, said in the presentation.
In the NEOSTAR phase 2 randomized study, patients with stage I through IIIA resectable NSCLC received neoadjuvant nivolumab or nivolumab plus ipilimumab, followed by surgery. Investigators defined treatment failure as lung cancer recurrence and/or death related to treatment or disease, according to the abstract.
Out of 44 patients evaluated, 37 were resected during the trial and seven were unresected or resected off-trial. Of those resected on-trial, eight (22%) experienced treatment failure compared with five (71%) who were unresected or were resected off-trial had treatment failure. Of the 13 treatment failures between both arms, 11 were defined by recurrence and of those, 10 were categorized as distant recurrences.
TKI-sensitive aberration was present in eight (73%) of 11 profiled patients who experienced treatment failure, and patients with TKI-sensitive aberration had a shorter time before treatment failure (median, 18.5 months) than patients without aberration. The HR for treatment failure with aberration was 8.66.
Immuno-oncology based therapy was used in retreatment of four patients, three of whom had TKI-sensitive aberration.
Investigators did not note any significant increased risks related to demographics, clinical stage, histology, major pathological response status or pretreatment PD-L1 status. Smokers were less likely than never-smokers to experience TF (HR = 0.25); 80% of smokers with TF had TKI-sensitive aberration, according to the presentation.
“It's important to recognize that 73% of treatment failures and 80% of recurrences had a TKI-sensitive genomic aberration,” Zhou said. “Benefit of retreatment with [immuno-oncology] is unclear since three out of the four treated with [immuno-oncology] again had a TKI-sensitive genomic aberration.”
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Zhou N. et al. Abstract 8542. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021 (virtual meeting).
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