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NSCLC Year in Review Introduction

2021 Year in Review - Non–Small-Cell Lung Cancer - Lung Cancer

Colleagues,

The COVID-19 pandemic continues to impact healthcare across the globe. We are yet to see the full effect of the COVID-19 pandemic on patients with cancer, including patients with non–small-cell lung cancer (NSCLC). With the recent emergence of the COVID-19 Omicron variant, we expect this impact on healthcare and cancer care to continue. The Year in Review series is an important tool to reach audiences and provide timely and relevant information on treatment advances in the oncology setting.

This Year in Review is focused on NSCLC. Lung cancer is the second most frequent cancer in both men and women, and the leading cause of cancer death globally. NSCLC accounts for more than 80% of lung cancers, and most patients have advanced disease with poor prognosis. However, in recent years, advances in molecular modeling and improved understanding of biochemical mechanisms driving NSCLC have led to the development of novel treatments and improved outcomes. In May 2021, sotorasib was granted accelerated approval by the US Food and Drug Administration for the treatment of KRASG12C–mutated locally advanced or metastatic NSCLC after demonstrating unprecedented clinical activity in the CodeBreaK 100 trial. KRAS now joins a growing list of actionable mutations in NSCLC, giving many patients hope with a new treatment option.

In a recent study of the US Flatiron database, a cohort of anaplastic lymphoma kinase–positive and a cohort of non–biomarker-positive metastatic NSCLC patients diagnosed between 2012 and 2019 were presented at the 2021 annual meeting of the American Society of Clinical Oncology. The goal of this study was to determine the impact of targeted therapy and immunotherapy on lung cancer mortality. It was found that both targeted therapy and immunotherapy in patients with NSCLC have increased survival rates in recent years, further supporting the development of novel treatments that target actionable driver mutations or activate the antitumor immune response.

A study was performed in China between 2017 and 2020 to investigate the mechanism of immune checkpoint inhibitor (ICI) efficacy in Chinese patients with NSCLC with KRAS mutations. KRAS is the most common oncogenic driver mutation in NSCLC and frequently co-occurs with STK11 mutations, which have recently been identified as an important subtype of NSCLC that is resistant to ICIs. The study showed that differences in tumor immune microenvironment, which includes immune cell infiltrates and PD-L1 expression, was significantly associated with the divergent response to ICI in patients with KRAS mutations, STK11 mutations, and KRAS/STK11 co-mutations. Therefore, in addition to the type of KRAS variant (ie, G12C, G12V, G12D, etc), the existence of co-mutations clearly has an impact on the biology of KRAS-driven illnesses and the response to treatment.

ICI therapy has significantly improved survival rates in patients with NSCLC but can often lead to immune-related adverse effects that may necessitate dose delays, reductions, or treatment discontinuation. This Year in Review discusses ICI-induced pneumonitis, a relatively uncommon but particularly serious immune-related adverse effect. Early recognition of ICI-induced pneumonitis and prompt administration of steroids often improves symptoms. However, some patients develop chronic pneumonitis despite long-term steroid use. Here, additional immunomodulators showed a reduction in pneumonitis in more than one-third of patients. In the future, better knowledge of the underlying biology of immune-related pneumonitis will be essential for developing more precise and effective treatment techniques.

Cancer-related fatigue is common over the course of the disease and is the most commonly reported symptom in patients with lung cancer. Cancer treatments can also cause patient fatigue but exercise has tremendous benefits for the cancer patient, including better disease outcomes. Finding the optimal balance is discussed in the Year in Review.

Next-generation sequencing (NGS) is becoming more important in cancer diagnostics for NSCLC, given the implications for therapeutic decisions. There are still several obstacles to NGS adoption, and we look at a study to uncover physician-identified barriers in this Year in Review. NGS testing will play an important role in the future of cancer treatment and breaking the barriers to testing is an important step in improving patient outcomes.

A number of other important and interesting results were observed across the studies discussed in this Year in Review. These results will benefit patients with NSCLC and improve their outcomes in years to come.

We are pleased to present these key topics in NSCLC in this Year in Review.

Rajwanth Veluswamy, MD, MSCR
Assistant Professor of Medicine
Thoracic Oncology, Tisch Cancer Institute
Institute for Translational Epidemiology
Icahn School of Medicine at Mount Sinai

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