Over the past year, the COVID-19 pandemic has ushered in unprecedented changes in the practice of medicine and dissemination of treatment advances presented in scientific forums. Adapting to the changes, organizations such as the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and International Association for the Study of Lung Cancer (IASLC) have adopted abbreviated virtual formats for their national and international meetings that delivered cutting-edge research in the advancement of oncology care. Recognizing the challenges of the virtual format in terms of reach and impact, we are bringing the Year in Review series that seeks to synthesize the presented treatment advances and disseminate the information to clinicians in a timely and effective manner to support cancer care delivery and research.
This edition of Year in Review is focused on non–small-cell lung cancer (NSCLC), which is characterized by a high degree of molecular and genetic heterogeneity that gives rise to different pathways driving tumor evolution and progression as well as mechanisms of treatment response and resistance. In 2020, the US Food and Drug Administration approved 5 novel targeted agents for NSCLC—capmatinib, selpercatinib, pralsetinib, lurbinectedin, and osimertinib. Below is a quick review of some of the topics discussed in this issue, with a focus on key data supporting recent drug approvals, current therapeutic advances, and potentially practice-changing developments in NSCLC.
Increased understanding of the NSCLC genetic landscape has led to identification of new actionable alterations such as MET exon 14 skipping mutations, MET amplifications, and RET fusions for which therapeutic interventions are being developed and actively investigated, as well as novel approaches to EGFR and ALK mutations. Results of the phase 2 GEOMETRY mono-1 study showed that capmatinib, an oral cMET inhibitor, had clinical benefit in patients with MET exon 14–mutated or MET-amplified NSCLC. In addition, capmatinib in combination with the EGFR tyrosine kinase inhibitor (TKI) nazartinib demonstrated clinically relevant efficacy and was well tolerated in patients with EGFR-mutant NSCLC who progressed on EGFR-TKIs.
In the registrational phase 1/2 trial LIBRETTO-001, selpercatinib, an oral RET inhibitor, demonstrated antitumor activity in patients with RET fusion–positive NSCLC and central nervous system metastases, with durable responses in previously treated patients. Another oral RET inhibitor, pralsetinib, was shown to have marked and durable antitumor activity in patients with RET fusion–positive NSCLC based on the results of the phase 1/2 ARROW study.
Osimertinib, an irreversible oral EGFR-TKI that selectively inhibits EGFR-TKI–sensitizing and EGFR T790M–resistance mutations, has shown promising activity in untreated, EGFR-mutated advanced NSCLC. Results of the phase 3 FLAURA trial showed that osimertinib was associated with significantly longer overall survival versus comparator EGFR-TKIs and had a similar safety profile in this patient population. In the phase 3 ADAURA trial, osimertinib was shown to be effective in the adjuvant setting for patients with stage IB to IIIA EGFR mutation–positive NSCLC.
Other important research efforts have yielded findings that support the use of targeted agents in EGFR-mutated NSCLC (afatinib, gefitinib, patritumab deruxtecan), HER2-mutated NSCLC (trastuzumab deruxtecan, poziotinib), and ALK-positive NSCLC (alectinib, lorlatinib, ensartinib).
We are pleased to present the highlights of these topics and more!
David Spigel, MD
Chief Scientific Officer
Director, Lung Cancer Research Program
Sarah Cannon Research Institute