Treatment for early-stage, resectable non-small cell lung cancer (NSCLC) has evolved rapidly in recent years with the introduction of targeted therapies and immunotherapy. While these advances have improved outcomes for many patients, important questions remain about when these treatments should be used
At this year’s ASCO Annual Meeting, Raymond U. Osarogiagbon, MBBS, FACP, FASCO, discussed the growing role of systemic therapy in resectable NSCLC and the ongoing debate surrounding neoadjuvant, adjuvant, and perioperative treatment approaches.
Although several therapies are now approved in early-stage disease, Dr. Osarogiagbon emphasized that many questions about treatment timing remain unanswered. “The current guidelines for the preferential use of chemoimmunotherapy are not currently evidence-based,” he said.
Surgical resection remains the cornerstone of treatment for patients with resectable NSCLC. However, recurrence rates remain substantial, ranging from approximately 25 to 70 percent depending on disease stage.
Because many recurrences occur at distant sites, systemic therapies are increasingly used before or after surgery to reduce recurrence risk and improve long-term outcomes.
The challenge, according to Dr. Osarogiagbon, is determining which patients benefit most from treatment before, after, or during the perioperative period.
Targeted therapies have become an important component of treatment for patients whose tumors harbor specific genetic alterations.
Dr. Osarogiagbon highlighted the growing body of evidence supporting adjuvant targeted therapy for patients with EGFR- and ALK-positive NSCLC. Adjuvant osimertinib is approved for eligible patients with EGFR-mutated disease, while adjuvant alectinib has demonstrated benefit for patients with ALK-positive tumors.
Additional targeted therapies are also being investigated for patients with RET, ROS1, KRAS G12C, and other actionable mutations.
As treatment options expand, comprehensive biomarker testing is becoming increasingly important in early-stage disease to help guide treatment decisions.
While targeted therapies have become more clearly defined for certain patient populations, the optimal use of immunotherapy remains less certain.
Multiple FDA-approved options now exist for patients with resectable NSCLC, including neoadjuvant, adjuvant, and perioperative chemoimmunotherapy approaches. However, direct comparisons between these strategies are lacking.
Dr. Osarogiagbon reviewed several potential advantages and disadvantages of each approach. Neoadjuvant therapy may help treat microscopic disease earlier and provide information about treatment response, but it can also delay surgery and potentially expose some patients to unnecessary treatment. Adjuvant therapy ensures patients undergo surgery first, but it may result in some patients never receiving planned systemic therapy.
Ultimately, he argued that the oncology community still lacks definitive evidence regarding which strategy is best.
Several ongoing studies are attempting to address these unanswered questions.
Dr. Osarogiagbon highlighted trials such as PROSPECT-Lung and INSIGHT, which are evaluating different approaches to treatment sequencing and duration in patients with resectable NSCLC.
He encouraged clinicians to support clinical trial enrollment whenever possible to help generate the evidence needed to guide future treatment decisions.
“We need to generate the evidence,” he said.
Targeted therapies and immunotherapy are continuing to reshape treatment for patients with early-stage, resectable NSCLC. While therapies such as osimertinib and alectinib have established roles for patients with specific mutations, significant questions remain about the optimal timing of systemic treatment for many patients.
Dr. Osarogiagbon’s presentation underscored the importance of biomarker testing, individualized treatment planning, and ongoing participation in clinical trials as researchers work to determine which patients benefit most from neoadjuvant, adjuvant, or perioperative approaches.
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