DURHAM, NC—Not that long ago, chemotherapy (CT) using multi-agents was considered the standard of care for advanced non-small cell lung cancer (NSCLC) patients.
More recently, with the publication of clinical trials, immunotherapy (IO) has been shown to have benefits for improving overall survival (OS) and progression-free survival compared to CT.
A recent study led by the Durham, NC, VA Healthcare System and Duke University compared real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC.
The retrospective study published in PLoS One included patients in the VA patients diagnosed with stage IV NSCLC from 2012-2017 and receiving IO or CT in the 2L. Researchers compared patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) between treatment groups.
The study reported that 4,609 veterans received first-line (1L) therapy for stage IV NSCLC, of which 96% received 1L CT alone. As for the 1,630 (35%) receiving 2L systemic therapy, 695 (43%) had IO and 935 (57%) had CT.
The median ages were similar — 67 years in the IO group and 65 years in the CT group. Most patients were male (97%) and white (76-77%).
Results indicated that patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). “2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75-0.94),” the authors advised. “IO was more frequently prescribed during the study period (p < 0.0001). No difference in rate of hospitalizations was observed between the two groups.”
Pointing out that, “overall, the proportion of advanced NSCLC patients receiving 2L systemic therapy is low,” the study recommended that, for patients treated with 1L CT and without IO contraindications, “2L IO should be considered, as this supports potential benefit of IO for advanced NSCLC. The increasing availability and indications for IO will likely increase the administration of 2L therapy to NSCLC patients.”
Background information in the study pointed out that lung cancer is the second most common cancer and the leading cause of cancer-related death among men and women in the United States, with non-small cell lung cancer (NSCLC) being the predominant histologic subtype. NSCLC makes up about 87% of lung cancer cases and usually is diagnosed at an advanced stage. “Before the era of immunotherapy (IO), the 5-year survival rate for patients with advanced NSCLC was only 5%, and even with modest improvements remain less than 10%,” the authors added..
Previous to 2015, according to the study, the standard of care for metastatic NSCLC was platinum-based chemotherapy (CT). “However, in recent years, the therapeutic landscape has changed rapidly with the development of a range of new treatments,” the researchers recounted. “In addition to targeted therapies for patients with actionable gene mutations, a number of immune checkpoint inhibitors have now been approved for use in both first-line (1L) and second-line (2L) treatment settings for patients with metastatic NSCLC regardless of the results of biomarker testing.”
They added that “ IO therapies have been demonstrated to significantly improve progression-free survival (PFS) and overall survival (OS) in comparison to CT. Studies have also shown that IO has an acceptable toxicity profile in comparison to other therapies.”
The study decried the lack of real-world studies of IO therapy effectiveness and safety, however. “Clinical trials are highly selective, and few adult cancer patients are eligible for clinical trials,” the authors explained. “For those who are candidates, they tend to be relatively young and healthy, in contrast to the mostly elderly general population of patients with metastatic NSCLC seen in general oncology practice. For example, approximately 70% of patients with NSCLC would fail to meet the inclusion criteria for the clinical trials used to approve these treatments. Moreover, in comparison to patients in clinical trials, patients with NSCLC treated with programmed cell death protein 1 inhibitors within community cancer care clinics were older when treatment was initiated and had reduced OS. Such findings suggest that the benefits of IO may not be as pronounced in comparison to CT in a real-world setting.”
- Williams CD, Allo MA, Gu L, Vashistha V, Press A, Kelley M. Health outcomes and healthcare resource utilization among Veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy. PLoS One. 2023 Feb 21;18(2):e0282020. doi: 10.1371/journal.pone.0282020. PMID: 36809528; PMCID: PMC9942992.