Targeted Therapy and Immunotherapy May Improve NSCLC Survival Rates

Non–small-cell lung cancer (NSCLC) has an overall poor 5-year survival rate, particularly when the disease is diagnosed at advanced stages.¹ Certain prognostic factors for NSCLC long-term survival have been identified. These include being diagnosed with adenocarcinoma rather than squamous-cell carcinoma, fewer sites of metastasis or few involved lymph nodes, metastasis that is limited to the brain or thorax, being a nonsmoker or a former smoker, and normal lactate dehydrogenase levels at diagnosis.¹

Treatment has also been associated with long-term NSCLC survival. Having a longer response to first-line chemotherapy or a more appropriate first-line chemotherapy, curative surgery, a greater number of chemotherapy agents, the use of maintenance therapy, better performance status, or treatment with immunotherapy or with epidermal growth factor receptor tyrosine kinase inhibitors have all been factors associated with long-term survival, but because of variation in definitions, patient differences, and small sample sizes, interpretation of these factors is restricted.¹

The Surveillance, Epidemiology, and End Results program data have recently indicated that there has been significant mortality improvement in patients with NSCLC in the United States over the past 2 decades.² However, why this improvement has occurred is not clear, because there have been few studies that have directly investigated these improvements. From 2015 to 2019, the hazard of death in non–biomarker-positive patients (after adjustment for baseline characteristics) had a steady decrease each year. In 2015, there was a 14% decrease from 2012 and in 2019 there was a 21% decrease from 2012.²

Recently, the results of a study utilizing the US Flatiron database to identify a cohort of ALK-positive (ALK+) patients and a cohort of non–biomarker-positive metastatic NSCLC (mNSCLC) patients diagnosed between 2012 and 2019 were presented at the 2021 American Society of Clinical Oncology annual meeting. This study attempted to determine if an improvement in mortality was associated with the introduction of targeted therapy and immunotherapy. In the non–biomarker-positive mNSCLC patient cohort, 30,076 patients were identified and in the ALK+ cohort 652 patients were identified.² More than half (54.7%) of the mNSCLC patients were male and 45.4% of the ALK+ cohort patients were male.²

Both cohorts had an improvement in survival over time. After adjustment for use of first- or second-line immunotherapy in the mNSCLC cohort and ALK inhibitors in the ALK+ cohort, the decrease in the hazard of death by calendar year was no longer observed.² These findings indicate the use of targeted therapy and immunotherapy in patients with NSCLC has improved the survival in this patient population over the past decade.

References

1. Davis JS, Prophet E, Peng HL, et al. Potential influence on clinical trials of long-term survivors of stage IV non-small cell lung cancer. JNCI Cancer Spectr. 2019;3:pkz010.
2. Ramagopalan S, Leahy T, Ray J, et al. Association between improvements in survival of metastatic NSCLC patients and targeted- and immuno-therapy. J Clin Oncol. 2021(suppl_15):abstr 9090.