Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly
defined by genetic alterations in oncogenic drivers. Targeted therapies
have transformed the management of oncogene-driven lung cancers, with
targeted agents now approved in the United States for 7 distinct
molecular alterations. Nonetheless, acquired resistance remains an
ongoing challenge, underscoring the need for alternative therapeutic
approaches. Immune checkpoint inhibitors targeting the programmed cell
death 1 (PD-1) axis have emerged as important therapies in the
management of advanced NSCLC, but the role of these agents in patients
with oncogenic driver mutations remains unclear. Here, we focus on
epidermal growth factor receptor-mutant and anaplastic lymphoma
kinase-rearranged NSCLC as paradigms to explore the role of immune
checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview
of the clinical data examining programmed death ligand 1 (PD-L1)
inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor
combinations, as well as combinations of PD-(L)1 inhibitors and
chemotherapy. READ ARTICLE
Cancer Journal DOI:10.1097/PPO.0000000000000491
Authors: Gavralidis A, Gainor JF
Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients.In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent. READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.10.006
Authors: Enriqueta Felip, Filippo G. de Braud, Michela Maur, Herbert H. Loong, Alice Tsang Shaw, Johan F. Vansteenkiste, Thomas John, PGeoffrey Liu, Martijn P. Lolkema, Giovanni Selvaggi, Vanessa Giannone, Pilar Cazorla, Jason Baum, O. Alejandro Balbin, Luojun (Victor) Wang, Yvonne Y. Lau, Jeffrey W. Scott, Daniel Shao-Weng Tan