Targeted Therapy and Immunotherapy May Improve NSCLC Survival Rates

2021 Year in Review: Non–Small-Cell Lung Cancer —December 29, 2021


Lung Cancer

The 5-year survival rate for patients with non–small-cell lung cancer (NSCLC) is generally poor, especially when the illness is diagnosed at an advanced stage.1 Long-term survival of patients with NSCLC has been linked to a number of prognostic variables. Being diagnosed with adenocarcinoma rather than squamous-cell carcinoma, having fewer sites of metastasis or few involved lymph nodes, having metastasis limited to the brain or thorax, being a nonsmoker or former smoker, and having normal lactate dehydrogenase levels at diagnosis are just a few of the factors.1

Long-term NSCLC survival has also been linked to treatment. Longer responses to first-line chemotherapy or more appropriate first-line chemotherapy, curative surgery, a greater number of chemotherapy agents, maintenance therapy, better performance status, or treatment with immunotherapy or epidermal growth factor receptor tyrosine kinase inhibitors have all been linked to long-term survival, but interpretation of these variables has been difficult due to differences in definitions, patient differences, and small sample sizes.1

According to statistics from the SEER program, there has been a significant reduction in mortality in individuals with NSCLC in the United States during the past 2 decades.2 However, because there has been little research in these mortality reductions, it has been unclear why these improvements occurred. The risk for death in patients with non–biomarker-positive disease (after adjusting for baseline variables) decreased steadily from 2015 to 2019. There was a 14% decline in 2015 compared with 2012, and a 21% decrease in 2019.2

In a recent study of the US Flatiron database, a cohort of patients with anaplastic lymphoma kinase (ALK)-positive NSCLC and a cohort of patients with non–biomarker-positive metastatic NSCLC diagnosed between 2012 and 2019 were presented at the 2021 American Society of Clinical Oncology Annual Meeting. The goal of this trial was to determine if the introduction of targeted therapy and immunotherapy led to a decrease in mortality. There were 30,076 patients in the non–biomarker-positive metastatic NSCLC cohort and 652 patients in the ALK-positive cohort.2 Both groups showed improved survival rates over time. The decrease in the death rate by calendar year was no longer evident after accounting for the use of first- or second-line immunotherapy in the metastatic NSCLC cohort and ALK inhibitors in the ALK-positive cohort.2

This study showed that the use of targeted therapy and immunotherapy in patients with NSCLC has increased survival in this patient population, and the development of these innovative drugs that target actionable mutations in cancer cells have helped to improve lung cancer mortality over the past decade.3


  1. Davis JS, Prophet E, Peng H-L, 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 TP, Ray J, et al. Association between improvements in survival of metastatic NSCLC patients and targeted- and immuno-therapy. J Clin Oncol. 2021;39(suppl 15):Abstract 9090.
  3. Majeed U, Manochakian R, Zhao Y, Lou Y. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14:108.
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Last modified: December 29, 2021

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