Advanced Non-Small Cell Lung Cancer
Lung cancer at a glance
Non-small cell lung cancer (NSCLC) is the most common tumor type, accounting for approximately 85% of lung cancers.5 Despite the recent increase in the number of treatment options, lung cancer remains the most common cause of cancer death worldwide.1,2 Although patient outcomes are better if the disease is diagnosed in its early stages, the overall survival (OS) rate at one year for patients with advanced disease ranges from 60-70%, with 2-year OS rates of 46%.3,4
Developments in advanced NSCLC treatment
Targeting driver mutations in NSCLC
One of the most significant advances in the treatment of advanced/metastatic NSCLC has been the identification and targeting of driver mutations.6,7 Molecular drivers have been identified that represent strong predictive biomarkers and serve as therapeutic targets. Guidelines suggest that all patients with advanced adenocarcinoma should be tested for the presence of oncogenic drivers that can be therapeutically targeted. This includes broad molecular profiling of EGFR, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, and HER2 genes. Testing for these biomarkers is now considered mandatory in many countries.6,7
HER2-targeted therapies for NSCLC
Approximately 2-4% of non-squamous NSCLCs are driven by mutations in the HER2 gene.8 While chemotherapy and/or immunotherapy remain the first-line standard of care for patients with HER2-mutated NSCLC, a HER2-ADC is approved post-systemic therapy and HER2-targeted therapies are being studied and have the potential to replace current standard of care.7,9,10
NSCLC lacking targetable driver mutations
For NSCLC without driver mutations, recent advances in various treatment lines have included agents that inhibit angiogenesis, as well as immunotherapies that target the programmed cell death receptor 1 (PD-1) or programmed cell death ligand 1 (PD-L1).7,11 In recent treatment guidelines, anti-PD-1 and anti-PD-L1 have become the preferred first-line therapy for patients with tumors that are PD-L1 positive ≥50% and have no other targetable driver mutations.7,11 Combinations of chemotherapy with anti-PD-1 or anti-PD-L1 are recommended for those with tumors that are PD-L1 positive ≥1% to 49%.7,11
Molecular diagnostics and tailored treatment in NSCLC
Alongside treatments targeted to specific mutations, diagnostic techniques that identify these mutations in patients need to be developed. Ideally, a diagnostic test should be sensitive, non-invasive and fast enough to inform a treatment decision. Liquid biopsy is one such technique: plasma samples, rather than tumor samples, can be analyzed for the presence of mutations based on innovative new techniques like next-generation sequencing and digital droplet polymerase chain reaction (ddPCR).12
A large proportion of patients still exist with either squamous disease or non-squamous tumors that do not bear a driver mutation.6,7 In addition, while immunotherapy has been widely utilized, not all tumors respond to this class of treatment and almost all patients eventually relapse.13 Further research is needed to clearly identify which patient subgroups will benefit most from novel treatments such as immunotherapies, and what the optimal treatment options are when these novel treatments fail.
Bray F, et al. CA Cancer J Clin. 2018;68:394–424.
Ferlay J, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. https://gco.iarc.who.int/today (Accessed: February 2024).
Baraibar I, et al. Crit Rev Oncol Hematol. 2020;148:102906.
Isaacs J, et al. Ann Transl Med. 2020;8:517.
Molina JR, et al. Mayo Clin Proc. 2008;83:584–94.
Hendriks LE, et al. Ann Oncol. 2023;34:339-357.
National Comprehensive Cancer Network. NCCN Guidelines: Non-Small Cell Lung Cancer, Version 2.2024. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed: February 2024).
Riudavets M, et al. ESMO Open. 2021;6:100260.
US Food and Drug Administration. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung (Accessed: February 2024)
Businesswire. Spectrum Pharmaceuticals receives complete response letter from U.S. Food and Drug Administration for poziotinib. https://www.businesswire.com/news/home/20221125005059/en/Spectrum-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-Food-and-Drug-Administration-for-Poziotinib-Reaffirms-Focus-on-the-Commercialization-of-ROLVEDON%E2%84%A2-eflapegrastim-xnst-injection (Accessed: February 2024)
Hendriks LE, et al. Ann Oncol. 2023;34:358-376.
Schvartsman G, et al. Ther Adv Med Oncol. 2016;8:460–73.
Bordi P, et al. Lung Cancer. 2019;131:78–85.
You may also be interested in…
