Actionability of on-target ALK resistance mutations in patients with non-small cell lung cancer: local experience and review of the literature

ALK-fusion-positive NSCLC patients treated with ALK inhibitors frequently develop on-target resistance mutations. We provide clinical evidence for targeting these mutations with currently available inhibitors using a pooled population of 387 patients. The majority achieved clinical benefit, but the likelihood of clinical benefit differed for each mutation-inhibitor combination. Our comprehensive overview can facilitate guidance for treating similar patients in clinical practice. READ ARTICLE

Clinical Lung Cancer DOI: 10.1016/j.cllc.2021.06.011

Authors: Bart Koopman, Harry J.M. Groen, Ed Schuuring, T. Jeroen N. Hiltermann, Wim Timens, Wilfred F.A. den Dunnen, Anke van den Berg, Arja ter Elst, Michel van Kruchten, Joost L. Kluiver, Birgitta I. Hiddinga, Lucie B.M. Hijmering-Kappelle, Matthew R. Groves, Juliana F. Vilacha, Léon C. van Kempen and Anthonie J. van der Wekken

Review Paper, group4Kirk SmithJuly 1, 2021ALK, NSCLC, mutation, resistance, sensitivity

Clinical utility of tumor mutational burden in patients with non-small cell lung cancer treated with immunotherapy

Anti-programmed death (ligand)-1 [anti-PD-(L)1] therapies such as pembrolizumab, nivolumab or atezolizumab have become standard of care for non-small cell lung cancer (NSCLC) patients either in first line or beyond. PD-L1 expression level allows enriching the treated population with responders, but it is still not an optimal biomarker. Even in patients with PD-L1 tumor proportion score (TPS) levels of ≥50% treated with first line pembrolizumab overall response rate (ORR) is only 44.8% and overall survival at one year is 70%. Moreover, in combination trials with chemotherapy and anti-PD-(L)1 therapy, a significant proportion of patients does not respond (ORR ranges from 45.3% to 64.0%), regardless of PD-L1 expression. Furthermore, PD-L1 expression level is not associated with improved benefit in patients treated with combinations of anti-PD-(L)1 and anti-cytotoxic T-lymphocyte-associated antigen (anti-CTLA4) therapy. One of the new promising biomarkers is tumor mutational burden (TMB). ..... READ ARTICLE

Translational Lung Cancer Research DOI:10.21037/tlcr.2018.09.22

Authors: Lizza E. Hendriks, Etienne Rouleau and Benjamin Besse

Review PaperKirk SmithDecember 1, 2018Immunotherapy, mutation, immunology, non-small cell lung cancer (NSCLC), predictive value of tests, programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB)