Precision Advances Have Transformed Lung Cancer Care, But Key Barriers Persist

Advanced lung cancer management strategies have shifted from empiric, one-size-fits-all chemotherapy regimens to biomarker-driven precision approaches that have measurably improved survival outcomes, yet late diagnoses, uneven access to molecular testing and expertise, and persistent research underfunding continue to limit further progress, according to Christine M. Lovly, MD, PhD, FASCO.¹

In the Bonnie J. Addario Lectureship Award keynote lecture at the 27th Annual International Lung Cancer Congress®, Lovly traced the lung oncology field’s transformation through the story of Bonnie Addario, a late patient advocate who was diagnosed with stage III non–small cell lung cancer (NSCLC) in 2003. Lovly contrasted the “dark days” of that era with the targeted therapies and immune checkpoint inhibitors that define lung cancer care today. She also outlined the research and treatment barriers that remain for providers and patients alike.

Lovly is the division chief of Thoracic Medical Oncology, holder of the Dr. Norman and Melinda Payson Professorship in Medical Oncology, and a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope National Medical Center in Duarte, California.

How far has lung cancer care come since 2003?

In 2003, the year Bonnie was diagnosed, Lovly explained that an estimated 171,900 new lung cancer cases and 157,200 deaths were expected in the United States, and the 5-year relative survival rate from 1992 to 1998 was approximately 15%.^1,2 Lovly noted that this mortality-to-incidence gap was so narrow that most patients diagnosed with lung cancer died of the disease. She added that there were no recommended screening protocols and no approved checkpoint inhibitors or targeted therapies for lung cancer. Although gefitinib had received accelerated FDA approval in May 2003 for the treatment of patients with locally advanced or metastatic NSCLC following progression on platinum-based chemotherapy and docetaxel, this regulatory decision was not granted on the basis of mutational testing.³ For Bonnie’s surgically unresectable stage III disease, the 5-year survival rate was roughly 10% with SOC platinum-based chemotherapy plus radiation, without the immunotherapy or targeted consolidation therapy used today, according to Lovly.¹

The hallmarks of this era were captured by a 2002 ECOG trial comparing 4 platinum doublet regimens in patients with advanced NSCLC with no breakdown by histology and no biomarker stratification.⁴ In this study, the ORR was 19% (n = 1155), and the median overall survival (OS) was approximately 8 months across the different chemotherapy cohorts.

Then, in 2004, several bodies of research began to identify EGFR mutations as the reason a subset of patients experienced dramatic responses to gefitinib and erlotinib, Lovly highlighted. Findings from the phase 3 IPASS trial later confirmed that anti-EGFR therapy benefited patients with EGFR-mutant tumors and not those with EGFR wild-type disease.⁵

Do biomarkers matter in lung cancer management today?

Two paradigms now anchor NSCLC management: targeted therapies against oncogenic driver alterations, and ICIs that reactivate antitumor immunity, Lovly said. She pointed to data from prospective, biomarker-selected trials as evidence that precision therapy has moved the needle. In the phase 3 CROWN trial (NCT03052608), patients with newly diagnosed ALK-positive stage IV NSCLC who received the third-generation ALK inhibitor lorlatinib (Lorbrena; n = 149) had a median PFS that was not reached (95% CI, 64.3 months-not reached) vs 9.1 months (95% CI, 7.4-10.9) with the first-generation inhibitor crizotinib (Xalkori; n = 147).⁶ The HR was 0.19 (95% CI, 0.13-0.27) at a median follow-up of 60.2 months (95% CI, 57.4-61.6), and at 5 years, 60% (95% CI, 51%-68%) vs 8% (95% CI, 3%-14%) of patients, respectively, remained progression-free. Lovly framed these results as a dual lesson: that prospective biomarker testing matters, and that understanding targets has enabled the development of more effective drugs.

Regarding immunotherapy, she cited the KEYNOTE-024 trial (NCT02142738), in which first-line pembrolizumab (Keytruda; n = 154) for patients with metastatic NSCLC with a PD-L1 tumor proportion score of at least 50% produced a median OS of 26.3 months (95% CI, 18.3-40.4) vs 13.4 months (95% CI, 9.4-18.3) with chemotherapy (n = 151; HR, 0.62; 95% CI, 0.48-0.81), with respective 5-year OS rates of 31.9% vs 16.3%.⁷ Collectively, these data marked a shift “from empiricism to precision,” Lovly said, one that a 2020 analysis showed had reduced population-level NSCLC mortality rates as prospective genotyping was adopted.⁸

What barriers still stand in the way of progress in NSCLC management?

Despite the gains that have been made in lung cancer research and management over the past several years, this disease remains the leading cause of cancer death in the US for both men and women in 2026, accounting for approximately 20% of cancer deaths across both males and females.⁹ Additionally, for patients with metastatic lung cancer, the 5-year survival rate is only approximately 10%.

Lovly outlined 3 intertwined barriers:

Late diagnosis, compounded by screening gaps, low disease awareness, and stigma

Unequal access to molecular testing, subspecialty care, and clinical trials

Drug resistance as tumors adapt over time

The lung cancer screening uptake rate among eligible individuals was 17% in 2022, far below the corresponding rates for breast, cervical, and colorectal cancers.¹⁰ Additionally, lung cancer receives a relatively low amount of US federal research funding per death among the top 5 cancer killers, approximately $1,754 for NSCLC vs $69,800 for female breast cancer.¹¹

Progress, Lovly argued, now depends less on discovery than on delivery.

“Innovation is not our barrier,” she emphasized. “Implementation is.”

She positioned patient partnership as central to closing these gaps, alongside growing needs in survivorship research and protection of the cancer research workforce. Patient advocates, she said, increasingly shape clinical trial protocol design, end points, access, and data governance.

“Advocates sit at every table now,” Lovly concluded.

References

1. Lovly CM. #BeLikeBonnie. Honoring the past. celebrating today’s progress in lung cancer. Inspiring tomorrow’s breakthroughs. Presented at: 27th Annual International Lung Cancer Congress; July 24-25, 2026; Huntington Beach, California.
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3. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003;8(4):303-6. doi:10.1634/theoncologist.8-4-303
4. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med. 2002;346(2):92-98. doi:10.1056/NEJMoa011954
5. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-957. doi:10.1056/NEJMoa0810699
6. 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. J Clin Oncol. 2024;42(29):3400-3409. doi:10.1200/JCO.24.00581
7. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non–small-cell lung cancer with PD-L1 tumor proportion score ≥ 50%. J Clin Oncol. 2021;39(21):2339-2349. doi:10.1200/JCO.21.00174
8. Howlader N, Forjaz G, Mooradian MJ, et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383(7):640-649. doi:10.1056/NEJMoa1916623
9. Siegel RL, et al. Cancer statistics, 2026. CA Cancer J Clin. 2026;76(1). doi:10.3322/caac.70043
10. American Association for Cancer Research. AACR Cancer Progress Report 2025. AACR; 2025. Accessed July 29, 2026. https://cancerprogressreport.aacr.org/wp-content/uploads/sites/2/2025/09/AACR_CPR_2025.pdf
11. Mohindroo C, Thomas A. Incidence, mortality, and federal research funding by cancer type in the US. JAMA Netw Open. 2026;9(4):e267837. doi:10.1001/jamanetworkopen.2026.7837