lung cancer
Lung cancer research has been transformed by precision medicine, with EGFR, ALK, ROS1, KRAS G12C, and MET exon 14 alterations now serving as key targets for approved therapies. Clinical trials focus on identifying new actionable mutations, overcoming acquired resistance mechanisms, and combining targeted therapies with immunotherapy to deepen and prolong responses.
Trials investigate EGFR exon 20 insertion inhibitors, KRAS G12C inhibitors, bispecific antibodies, combination PD-1/CTLA-4 blockade, and consolidation immunotherapy after chemoradiation for locally advanced disease. Early detection studies using liquid biopsy and low-dose CT screening are also expanding.
Most trials require tissue or liquid biopsy for molecular profiling before enrollment to match patients to targeted therapies.
Disease Burden & Epidemiology
Lung cancer is the leading cause of cancer mortality worldwide, responsible for approximately 1.8 million deaths annually — more than colorectal, breast, and prostate cancers combined. Global incidence stands at approximately 2.2 million new cases per year. In the United States, the American Cancer Society estimates roughly 234,000 new cases and 125,000 deaths annually. Non-small cell lung cancer (NSCLC) accounts for about 85% of cases, with adenocarcinoma being the most common histological subtype; squamous cell carcinoma and large cell carcinoma comprise the remainder. Small cell lung cancer (SCLC), accounting for 15% of cases, is highly aggressive and almost exclusively associated with smoking. The five-year survival rate across all stages remains approximately 25%, but has improved substantially in stage IV NSCLC with targetable mutations — patients with EGFR-mutated disease treated with osimertinib achieve five-year survival rates exceeding 30% in trial populations. Tobacco smoking accounts for approximately 80–90% of lung cancer cases, but never-smokers represent a clinically distinct and growing population, particularly among Asian women with EGFR and ALK-rearranged adenocarcinoma.
Key Research Trends & Landmark Studies
The FLAURA trial established osimertinib (third-generation EGFR inhibitor) as standard first-line therapy for EGFR-mutated NSCLC, demonstrating a median overall survival of 38.6 months β€” the longest ever reported in this population. The CROWN trial showed lorlatinib superiority over crizotinib in ALK-rearranged NSCLC, with a three-year progression-free survival rate of 64%. The CodeBreaK 200 trial led to the first approval of sotorasib for KRAS G12C-mutated NSCLC, breaking a four-decade impasse against this oncogene. In immunotherapy, the PACIFIC trial established durvalumab consolidation after concurrent chemoradiation as standard for unresectable stage III NSCLC, and the ADAURA trial demonstrated dramatic improvement in disease-free survival with adjuvant osimertinib in resected EGFR-mutated NSCLC. Currently active trials include amivantamab plus lazertinib combinations for EGFR-mutated disease post-osimertinib, patritumab deruxtecan for HER3-expressing tumors, and multiple KRAS G12D inhibitor first-in-human studies.
Patient Guide: How to Find & Join a Trial
For newly diagnosed lung cancer patients, comprehensive molecular profiling of tumor tissue is essential before enrollment in any targeted therapy trial. Standard reflex testing in the US includes EGFR, ALK, ROS1, KRAS, BRAF, MET, RET, and NTRK, plus PD-L1 expression by IHC and TMB from NGS panels. If tissue is insufficient, liquid biopsy (cell-free DNA) can detect many actionable alterations. Never-smokers and light smokers with adenocarcinoma have the highest rates of targetable mutations and should insist on complete NGS profiling before starting any therapy. For patients with known targetable alterations, phase 1 trials of next-generation inhibitors may offer access to agents specifically designed to overcome resistance to approved drugs. Patients with stage III disease should be evaluated at centers with dedicated multidisciplinary tumor boards experienced in trimodality therapy and consolidation immunotherapy protocols.