Survival Trends Among Patients With Metastatic NSCLC Before and After the Approval of Immunotherapy in the US

In this interview with the Journal of Clinical Pathways, Yating Wang, MD, Ascension Providence Hospital, breaks down her study titled “Survival trends among patients with metastatic non-small cell lung cancer before and after the approval of immunotherapy in the United States: a surveillance, epidemiology, and end Results database-based study.” The study’s findings were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Please introduce yourself by stating your name, title, organization, and relevant professional experience.

My name is Yating Wang. I'm currently a third-year hematology oncology fellow at Ascension Providence Hospital in Southfield, Michigan, where I also serve as a clinical instructor for Michigan State University. I completed my medical degree at West China School of Medicine, Sichuan University, and my internal medicine residency at Weiss Memorial Hospital in Chicago. My professional experience includes research in oncology, particularly in the areas of immunotherapy for cancer and gene therapy. I've authored and co-authored several peer-reviewed publications, including our recent study on survival trends among patients with metastatic non–small cell lung cancer (NSCLC) before and after the approval of immunotherapy in the US, based on an analysis of the SEER database.

What led you and your colleagues to conduct this study?

Our team was motivated to conduct this study because of the significant impact that immunotherapy has had on the treatment of advanced NSCLC since their introduction. While multiple clinical trials have demonstrated improved outcomes and survival in both first-line and second-line settings for metastatic NSCLC, we noticed a gap in population-based studies evaluating survival trends after the introduction of immunotherapy.

Nivolumab was introduced in 2015 by the US Food and Drug Administration (FDA) as the first immunotherapy for advanced NSCLC and market, which was a pivotal moment in lung cancer treatment. That approval was based on landmark trials such as CheckMate 057 and CheckMate 017 and how the treatment showed significant survival benefits compared to standard second-line chemotherapy. However, while these clinical trials provided crucial evidence, we recognize that their controlled setting and their strict selection criteria might not fully represent the diverse patient population we see in everyday clinical practice. So, we saw an opportunity in the SEER database to conduct a large-scale population-based study that could provide insights into the real-world impact of immunotherapy on NSCLC. Our goal was to evaluate overall survival before and after the introduction of immunotherapy using 2015 as the pivotal year. We believe this study could offer valuable insights into how the advent of immunotherapy has impacted lung cancer treatment and patient survival, and how it possibly will guide future research directions.

What were the study methods?

Our study utilized the SEER database, which covers about 48% of the US population. We focused on data from 17 registries spanning from 2000 to 2020. We identified patients with metastatic NSCLC using ICD-O-3 morphology codes. Our inclusion criteria encompassed cases that were microscopically confirmed, actively followed, had known age, and were included in the research database. We excluded cases diagnosed via death certificate or autopsy, those alive without recorded survival time, small cell lung cancer (SCLC) cases, and those lacking pathological diagnosis or staging information.

To evaluate the impact of immunotherapy, we divided our study population into two cohorts: pre-immunotherapy era (2010 to 2014) and immunotherapy era (2015 to 2020). That division was based on FDA approval of nivolumab in 2015, marking the introduction of immunotherapy for NSCLC. We also conducted a subgroup analysis based on race, sex, age, income, and geographical area. We used the chi-square tests to assess baseline characteristics between two different groups. For survival analysis we conducted one-year, three-year, five-year, and median overall survival using Kaplan-Meier curves, comparing them with log rank tests. We also evaluated cancer-specific survival.

To account for potential confounding factors, we performed multivariate analysis using the Cox proportional hazard model, adjusting for age, sex, race, income, and geographical area. Our primary outcome measures were overall survival and cancer-specific survival comparing the pre-immunotherapy and immunotherapy eras. We considered a P-value of .05 or less as statistically significant, and this methodology allowed us to comprehensively evaluate the population-level impact of immunotherapy on NSCLC.

Can you summarize the main findings?

Overall Survival Improvement

The study found a significant improvement in overall survival in the immunotherapy era. One-year overall survival increased from 33.5% to 40.1%; five-year overall survival increased from 6.8% to 10.7%; and medium overall survival improved from seven to eight months. Cancer-specific survival also improved. One-year survival increased from 36.8% to 44%; five-year survival increased from 9% to 14.3%; and median overall survival improved from eight months to 10 months. Patients with brain metastasis also experienced improved cancer-specific survival. Medium overall survival improved from six months to eight months.

Multivariate Analysis

After adjusting for age, race, sex, income, and geographical area, the survival benefit in the immunotherapy era remained significant with adjusted hazard ratio of 0.83 with confidence interval of 0.8 to 0.84 subgroup. Analysis also revealed that survival benefit was evident across various subgroups, including different age groups, sexes, races, income levels, geographic areas, and brain metastasis status.

Factors Associated With Worse Survival

Older age at diagnosis and male gender were independent predictors of worse survival in both eras. African Americans had slightly worse survival outcomes compared to other races in both cohorts, though they did show improvement since the introduction of immunotherapy. Patients in less populated areas tended to have worse survival outcomes compared to those in more populated metropolitan areas.

What key takeaways from the study would you like to highlight?

The key takeaways of the study are significant population-level impact. Immunotherapy has led to substantial improvements in survival for patients with metastatic NSCLC in real-world settings and broad benefit. Survival improvements were observed across various demographic subgroups and geographic areas. Patients with brain metastasis also showed improved survival in the immunotherapy era.

While significant survival rates were lower than those reported in clinical trials, the study highlights the importance of real-world data. Despite overall improvements, disparities in outcomes persist for certain subgroups, including African Americans and patients in less populated areas.

The survival benefit of immunotherapy remained significant after adjusting for various factors in multivariable analysis. These findings support the continued use and development of immunotherapy strategies for metastatic NSCLC. The study also sets the stage for further research into optimizing immunotherapy benefits across all patient subgroups.

How can your findings potentially impact treatment strategies for NSCLC?

Regarding future direction we need to continue the long term follow up for these patients. While not directly addressing our study, the significant survival benefits observed can help make informed discussion and analysis of the cost effectiveness of immunotherapy in NSCLC treatment. Also, our findings may influence the design of future clinical trials, particularly in terms of patient selection, stratification, and the choice of control arms. Continuous effort to address disparities is also important, as highlighted by our study.