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Early-Stage NSCLC Expert Insights
New Developments in Systemic Therapy for Early-Stage NSCLC Management: Expert Answers to Your Questions

Released: November 08, 2024

Expiration: November 07, 2025

Beth Sandy
Beth Sandy, MSN, CRNP, FAPO
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Key Takeaways
  • Immunotherapy can be used in eligible patients with early-stage non-small-cell lung cancer.
  • Key clinical trials have shown that the addition of perioperative immunotherapy can greatly improve patient outcomes.

Treatment with immunotherapy has become a standard of care for early-stage non-small-cell lung cancer (NSCLC). In this commentary, I discuss the value of adding immunotherapy to the treatment regimen for these patients, including how biomarker testing can impact this treatment decisions. Improved patient outcomes following the addition of perioperative immunotherapy observed in key clinical trials are also highlighted.

What biomarker tests should be performed for patients with early-stage NSCLC to potentially guide treatment?

Beth Sandy, MSN, CRNP, FAPO: We now have 2 targeted therapies approved for patients with early-stage NSCLC who have actionable molecular alterations:

  • Osimertinib is approved as adjuvant therapy after tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. ​
  • Alectinib is approved as adjuvant treatment in patients following tumor resection of ALK-positive NSCLC (tumors ≥4 cm or node positive)​.

Therefore, at a minimum, EGFR and ALK mutational status should be assessed to determine treatment eligibility for patients with early-stage NSCLC.

Although elevated levels of PD-L1 expression are generally not required for immune checkpoint inhibitor therapy to be beneficial for patients with biomarker-negative NSCLC, I also like to see PD-L1 testing be performed, as the results may help with treatment decisions. For example, if I am unable to determine whether a patient can tolerate neoadjuvant chemoimmunotherapy and their PD-L1 test is negative, that may weigh in the decision of whether or not to use it.

A next-generation sequencing (NGS) panel can also provide information about the patient's disease, but their neoadjuvant treatment should not be delayed or withheld if these data are not available.

How does perioperative immune checkpoint inhibitor therapy fit into the treatment landscape for patients with early-stage NSCLC without EGFR or ALK driver mutations?

Beth Sandy, MSN, CRNP, FAPO: Although adjuvant postoperative chemotherapy was widely used in the past, there has recently been a shift to perioperative immunotherapy plus chemotherapy for patients with early-stage NSCLC starting in the neoadjuvant setting. Although immunotherapy is offered in the adjuvant setting, considerable benefit has been observed in clinical trials when immunotherapy plus chemotherapy is given in the preoperative setting, followed by adjuvant immunotherapy. Historically, when neoadjuvant chemotherapy was given alone, patients did not greatly benefit.  

Three key randomized clinical trials in which immunotherapy was added in the perioperative setting demonstrated improved outcomes: KEYNOTE-671, which examined platinum-based chemotherapy plus pembrolizumab, AEGEAN, which looked at platinum-based chemotherapy plus durvalumab, and CheckMate 77T, which examined platinum-based chemotherapy plus nivolumab. In KEYNOTE-671, 18.1% of patients achieved a pathologic complete response (pCR), meaning no viable tumor remained. The pCR rate in AEGEAN was 17.2%, and 25.3% in CheckMate 77T. In the chemotherapy alone arm of these trials, the pCR rate was similar across trials, only around 4%. These results show that adding immunotherapy to preoperative chemotherapy considerably improves response, and this is why oncology clinicians are now utilizing immunotherapy in the perioperative setting. Moreover, these trials demonstrated improved median event-free survival (mEFS), with values of around 29 to 34 months. KEYNOTE-671 also provided the 36-month overall survival (OS) rates, which were 71.3% in the pembrolizumab arm and 64% in the placebo arm, a statistically significant improvement. The key takeaway here is that perioperative immunotherapy has become a standard of care for curative-intent early-stage NSCLC.

What’s the current thinking on the need for continuing adjuvant immunotherapy as part of the perioperative therapy regimen?

Beth Sandy, MSN, CRNP, FAPO: Usually, more than 4 cycles of immunotherapy (which was what is provided as part of preoperative regimens in the trials listed above) are needed to provide long-lasting effects, though some patients achieve a complete response after 1 or 2. The problem is, there is no way of knowing which patients these are, so HCPs feel it is necessary to use adjuvant immunotherapy to maximize benefit.

What do you offer patients who experience metastatic recurrence after receiving perioperative chemoimmunotherapy?

Beth Sandy, MSN, CRNP, FAPO: If patients are on a single-agent adjuvant immune checkpoint inhibitor and metastasis occurs, I try to add platinum-based chemotherapy to the immunotherapy plan. However, insurance companies often want to deny this treatment claiming progression on immunotherapy. Appeals can be won by describing how patients progressed on single-agent immunotherapy and are now considered newly metastatic,, warranting a new setting where chemotherapy and immunotherapy can be implemented as standard of care, first-line therapy.

Your Thoughts?
What is your experience with perioperative immunotherapy or adjuvant targeted therapy when treating patients with early-stage NSCLC? Get involved in the discussion by answering the polling question and posting a comment.

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How often do you ensure that your patients with early-stage NSCLC have been tested for the actionable biomarkers EGFR del19/L858R and ALK fusions?

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