Author: Daniel A. Saez, MSc, Manager, LungMATCH Navigation Program
For many years, the treatment options given to patients diagnosed with early stage non-small cell lung cancer (NSCLC) was limited to surgery with or without chemotherapy to improve outcomes. However, like with metastatic NSCLC, the treatment landscape for patients with early-stage NSCLC has shifted much more towards a precision medicine approach. In this article we will give an overview of the new direction in treatment options before surgery (neoadjuvant), after surgery (adjuvant). In addition, other advances in surgery, recurrence and outcome prediction, as well as how screening may change in the coming future is discussed.
Neoadjuvant Treatment Advances
Treatment given before surgery (called neoadjuvant treatment) can be differentiated into neoadjuvant treatment based on immunotherapy and neoadjuvant treatment based on targeted therapies. Immunotherapy based neoadjuvant treatment is available to all patients, while targeted therapy based neoadjuvant treatment is only available to patients with select biomarkers matched to individual therapy options.
Use of Immunotherapies
In the current treatment landscape, there is only one existing approval for neoadjuvant immunotherapy-based treatment. However, at the world conference on lung cancer (WCLC) and the European Society for Medical Oncology (ESMO) Congress, researchers presented emerging data on two new modalities for neoadjuvant treatment: multiple immunotherapy combination neoadjuvant treatment and immunotherapy combined with radiation neoadjuvant treatment. In addition to these new modalities, data further validating the combination of a singular immunotherapy with chemotherapy as neoadjuvant treatment was presented.
Emerging Trials for Targeted Therapies
Researchers at WCLC and ESMO also gave updates on emerging trials for neoadjuvant targeted therapy options. As is the case with targeted therapy for patients with metastatic disease, neoadjuvant targeted therapies must be biomarker matched. This means that only patients with specific genetic changes, or mutations, in the cancer can receive the select neoadjuvant targeted therapies in trials. To date, there are clinical trials for patients with mutations in ALK, BRAF, EGFR, NTRK, RET, and ROS1 which were talked about at WCLC and ESMO.
Adjuvant Treatment Advances
Treatment given after surgery (called adjuvant treatment) can be differentiated into adjuvant treatment based on immunotherapy and adjuvant treatment based on targeted therapies. Immunotherapy-based adjuvant treatment is available to all patients, while targeted therapy-based adjuvant treatment is only available to patients with select biomarkers matched to the individual therapy options.
Use of immunotherapies
Clinical trial results were presented at WCLC and ESMO which further validated the use of immunotherapy as adjuvant care. There is already FDA approval to use adjuvant immunotherapy. However, continued research into this treatment option may be able to help scientists and doctors better understand which patients could benefit from adjuvant immunotherapy.
Emerging Trials for Targeted Therapies
The current treatment landscape for adjuvant targeted therapies only has approval for the use of targeted therapies for patients with early-stage NSCLC with a mutation in EGFR. However, trials are ongoing to determine if patients with mutations in ALK, BRAF, NTRK, RET, and ROS1 would benefit from adjuvant targeted therapies.
Advances in Surgery and Screening
While advances in neoadjuvant and adjuvant care are extremely exciting, surgery remains the main curative treatment for patients with early-stage NSCLC. Emerging research suggests that sublobar resection may be an option for older patients with smaller peripheral tumors who may not otherwise be good candidates for surgery. Additionally, for patients with a history of tobacco consumption or use, cessation periods greater than two months before surgery have contributed to a more positive patient experience. Lastly, for patients who are not surgery candidates, there is ongoing research exploring if radiation with or without immunotherapy can have curative outcomes.
Recurrence is one of the main concerns many patients have expressed with surgery. While neoadjuvant and adjuvant therapy can help ease this concern and have been shown to provide positive benefit in the outcomes of patients, doctors and scientists are beginning to better understand who might be more at risk for recurrence than others. Using circulating tumor DNA (ctDNA) and minimal residual disease (MRD), doctors can see how much if any of the tumor might be left that could not otherwise be detected by traditional scans. A lot of work is needed in this area, but associations with higher ctDNA and MRD have been made with recurrence. Doctors are hoping to use these measures to determine who needs adjuvant therapy and be more prepared to offer more effective treatments to patients at higher risk.
Arguably, the most important part of treatment for early-stage NSCLC is detection itself. The new treatment options are only effective ifthe cancer is discovered before it spreads. And more importantly, the option for curative surgery or radiation is commonly not an option. Traditionally, early detection is accomplished by low dose CT (LDCT) screening. While LDCT has been proven to be highly effective for NSCLC, the current guidelines on who qualifies for screening may restrict some people from having access to LDCT (learn more about these guidelines here). GO2 is optimistic that more people will have access to LDCT in the future.
Paving the way for new guidelines is a discovery that some people may be susceptible to developing lung cancer from air pollution was also presented at ESMO. People must have specific genetic predispositions, but scientists were able to identify and validate the phenomenon at a molecular level. This groundbreaking discovery has not prompted any changes yet, but the long-term effects could lead to innumerable people having unprecedented access to lifesaving screening.
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