Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis

Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. We find that neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies. READ ARTICLE

Indian Journal of Cancer DOI:10.4103/ijc.IJC_71_20

Authors: Pınar Gürsoy, Burcu Çakar, Deniz Nart, Erdem Göker

Real-World OutcomesKirk SmithSeptember 30, 2021ALK, NSCLC, crizotinib, AE, neutropenia, PFS

1196P Pre-existing and acquired mechanisms of resistance to lorlatinib in previously treated patients (pts) with ALK+ advanced non-small cell lung cancer (NSCLC)

Lorlatinib, a potent, brain-penetrant, 3rd-generation (gen) ALK/ROS1 tyrosine kinase inhibitor (TKI) active against most known resistance mutations, showed robust clinical activity in ALK+ or ROS1+ NSCLC in a Ph 1/2 study that enrolled mostly heavily pretreated pts with CNS metastases. We evaluated potential resistance mechanisms, pre-existing or acquired, and efficacy in these settings.Limitations apply to ctDNA analyses, but in this heavily pretreated group of pts with ALK+ NSCLC, presence of TP53 mutations at BL was potentially associated with decreased lorlatinib efficacy, while presence of bypass mechanism aberrations with reduced activity. Upon progression, ALK compound mutations and bypass mechanism aberrations emerged in ∼28% of pts. READ ARTICLE

Annals of Oncology DOI:10.1016/j.annonc.2021.08.1801

Authors: B.J. Solomon, J-F. Martini, A. Bearz, E.H. Tan, R. Soo, B. Besse, T.M. Bauer, D. Shepard, F. Toffalorio, A. Abbattista, E. Felip, A.T. Shaw, S. Viteri, D.R. Camidge, T. Seto, S-H.I. Ou

Conference PaperKirk SmithSeptember 1, 2021Lorlatinib, CROWN trial, crizotinib, CNS, AE

1199P Dose modification for the management of CNS adverse events in the phase III CROWN study of lorlatinib in non-small cell lung cancer (NSCLC)

In the ongoing phase III CROWN study (NCT03052608), lorlatinib, a 3rd-generation inhibitor of anaplastic lymphoma kinase (ALK), improved progression-free survival (PFS) and intracranial response rates vs crizotinib in patients with previously untreated ALK-positive NSCLC. Here we present data on lorlatinib dose modification for the management of CNS adverse events (AEs). CNS AEs spontaneously resolved in 53% of cases, and lorlatinib dose modification was effective in managing CNS AEs without compromising efficacy. READ ARTICLE

Annals of Oncology DOI:10.1016/j.annonc.2021.08.1804

Authors: B.J. Solomon, T.S.K. Mok, H. Hayashi, A. Bearz, K.D. Penkov, Y-L. Wu, O. Arrieta, A.M. Calella, G. Peltz, A. Polli, H. Thurm, T.M. Bauer