Lung cancer is the leading cause of cancer death worldwide, and it increasingly affects people who have never smoked. But no cancer has been transformed more by precision medicine. Most non-small cell lung cancers are now treated according to the specific genetic change driving them, and in 2025 and 2026 several trials set new survival records. This article explains the tests that decide treatment, the newest results, and what patients can do themselves.
Screening Saves Lives: The Dutch-Belgian NELSON Trial
In the NELSON trial in the Netherlands and Belgium, men who were current or former heavy smokers and were screened with low-dose CT scans had 24 percent fewer lung cancer deaths over ten years than men who were not screened, and the benefit in the smaller group of women studied appeared even larger.1 Screening finds lung cancer early, when surgery can cure it.
The Tests Every Patient Needs
For non-small cell lung cancer, especially adenocarcinoma, comprehensive testing for driver mutations is essential before treatment begins: EGFR, ALK, ROS1, BRAF, KRAS G12C, MET, RET, HER2, NTRK and NRG1, plus PD-L1 for immunotherapy. Many of these targets, particularly gene fusions, are best found with RNA sequencing: in lung cancers with no driver found by DNA testing, RNA sequencing found a treatable fusion in about one in seven. See our article on tumor DNA and RNA sequencing. When tissue is limited, a ctDNA blood test can find many of the same mutations.
EGFR-Mutated Lung Cancer: New Survival Records
EGFR mutations are the most common driver in never-smokers. Two strategies set new records in 2025:
Osimertinib plus chemotherapy. In the FLAURA2 trial, whose final results were presented in September 2025 by David Planchard of Gustave Roussy in Paris, adding chemotherapy to the targeted drug osimertinib extended median overall survival to 47.5 months, compared with 37.6 months with osimertinib alone. At three years, 63 percent were alive with the combination, compared with 51 percent.2
Amivantamab plus lazertinib. In the MARIPOSA trial, published in the New England Journal of Medicine in September 2025, this combination of an antibody and a targeted pill improved overall survival compared with osimertinib alone, including in patients with brain metastases.3
ALK-Positive Lung Cancer
ALK-positive lung cancer often affects younger never-smokers. In the CROWN trial, 60 percent of patients treated first with the targeted drug lorlatinib were still free of progression after five years, an unprecedented result for metastatic lung cancer.4
Immunotherapy and a Chinese Breakthrough
For lung cancers without a targetable driver, immunotherapy, alone or with chemotherapy, is the foundation. A new class of drug developed in China, ivonescimab, blocks both the immune brake PD-1 and the blood vessel growth signal VEGF in a single molecule. In the Chinese HARMONi-2 trial, ivonescimab was compared head to head with pembrolizumab, the world’s leading immunotherapy drug, in PD-L1-positive advanced lung cancer, and in September 2026 the trial reported that ivonescimab significantly extended overall survival. In the HARMONi-6 trial in squamous lung cancer, ivonescimab with chemotherapy extended median progression-free survival to 11.1 months, compared with 6.9 months with standard immunotherapy and chemotherapy.5
For earlier-stage disease, immunotherapy given before and after surgery now improves outcomes, and ctDNA testing after surgery can show who still has hidden cancer.
Small Cell Lung Cancer
Small cell lung cancer grows fast and has had few advances for decades. In the DeLLphi-304 trial, led by Giannis Mountzios in Athens and published in 2025, tarlatamab, an antibody that links the patient’s T cells to a protein on small cell cancer cells, extended median overall survival to 13.6 months, compared with 8.3 months with chemotherapy, in patients whose cancer had progressed after first treatment.6
What Patients Can Do
Stop smoking, even after diagnosis. In a review of studies published in the BMJ, people with early-stage lung cancer who quit smoking after diagnosis lived longer than those who continued.7
Be cautious with antibiotics around immunotherapy. Researchers at Gustave Roussy found that patients who took antibiotics shortly before starting immunotherapy had worse outcomes, likely because antibiotics disrupt the gut bacteria that help the immune system respond.8 Antibiotics are sometimes essential, but unnecessary courses are worth avoiding.
Test the home for radon, the leading cause of lung cancer in never-smokers, and stay physically active, which supports strength and tolerance of treatment.
How Cancer Expert MD Helps
Cancer Expert MD specializes in education and consultation for people with Stage IV and metastatic cancer. When a targeted drug stops working, re-testing often reveals the resistance mechanism and the next option. Our guide to what to do when treatment stops working explains the steps, and our book, The New Reality of Cancer, covers testing and treatment across all cancers.
Frequently Asked Questions
What tests are needed for lung cancer?
Comprehensive testing for driver mutations, including EGFR, ALK, ROS1, BRAF, KRAS G12C, MET, RET, HER2, NTRK and NRG1, ideally with both DNA and RNA sequencing, plus PD-L1.
How long can you live with EGFR-mutated lung cancer?
In the FLAURA2 trial, median overall survival with osimertinib plus chemotherapy reached 47.5 months, nearly four years, and many patients live longer.
What is ivonescimab?
A drug developed in China that blocks both PD-1 and VEGF. In the HARMONi-2 trial it extended survival compared with pembrolizumab in PD-L1-positive advanced lung cancer.
Does quitting smoking help after a lung cancer diagnosis?
Yes. People with early-stage lung cancer who quit after diagnosis lived longer than those who kept smoking.
About the author. Dr. Silver, MD, graduated from Temple University School of Medicine, trained as an interventional cardiologist, and has practiced medicine for nearly fifty years. A lymphoma survivor of about twenty-five years, he is co-author, with Dr. Lindmeier, DHSc, of The New Reality of Cancer: The Science of Recovery. Read more about Dr. Silver, MD.
Research by Dr. Lindmeier, DHSc, cancer educator and co-author of The New Reality of Cancer.
More articles on cancer types and all articles.
References
- de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial (NELSON). New England Journal of Medicine. 2020;382(6):503–513.
- FLAURA2: first-line osimertinib plus chemotherapy versus osimertinib monotherapy in EGFR-mutated advanced NSCLC, final overall survival. Presented by Planchard D at the IASLC World Conference on Lung Cancer, September 2025.
- Yang JCH, Lu S, Hayashi H, et al. Overall survival with amivantamab–lazertinib in EGFR-mutated advanced NSCLC (MARIPOSA). New England Journal of Medicine. Published online 7 September 2025.
- Solomon BJ, Liu G, Felip E, et al. Lorlatinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer: 5-year outcomes from the phase III CROWN study. Journal of Clinical Oncology. 2024;42(29):3400–3409.
- HARMONi-2 overall survival interim analysis, IASLC World Conference on Lung Cancer, September 2026; HARMONi-6, ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous NSCLC, 2025.
- Mountzios G, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy (DeLLphi-304). New England Journal of Medicine. 2025.
- Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569.
- Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Annals of Oncology. 2018;29(6):1437–1444.
This article is for education only. It is not medical advice and does not diagnose or treat any condition. Cancer Expert MD has no financial relationship with any laboratory, drug maker, supplement company, clinic or hospital.
Response
[…] Common examples are pembrolizumab (Keytruda) and nivolumab (Opdivo), which block PD-1; ipilimumab (Yervoy), which blocks CTLA-4; and relatlimab, which blocks LAG-3. China has developed its own PD-1 drugs, including toripalimab, sintilimab and tislelizumab, and ivonescimab, which blocks PD-1 and the blood-vessel signal VEGF at the same time and has outperformed pembrolizumab in lung cancer. See our article on lung cancer treatment. […]