Meta-Analysis Challenges the Role of Adjuvant Immunotherapy in Early-Stage Non-Small Cell Lung Cancer: 'Less is More,' Says Researchers

A new meta-analysis published today in JAMA Network Open suggests that adding adjuvant immunotherapy may not improve outcomes for patients with early-stage non-small cell lung cancer (NSCLC) who receive neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy and undergo surgery.

Up to 30% of patients with NSCLC initially have resectable disease, meaning the tumor can be mostly removed via surgery. Unfortunately, 30% to 55% of these patients experience recurrence and eventual death from the disease, even after surgical removal.

In attempt to improve outcomes, the use of newer drugs including immune checkpoint inhibitors and targeted therapies has become more common as adjuvant and neoadjuvant systemic therapy for NSCLC.

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Adjuvant therapy refers to treatment given after surgery to remove the tumor in order to treat any remaining cancer cells. In contrast, the term neoadjuvant refers to treatment given before the surgery. However, given the new landscape of treatment options, debates exist surrounding the best approach to treating resectable NSCLC.

PD-1/PD-L1 inhibitors are a subclass of immune checkpoint inhibitors. Examples include Opdivo (nivolumab), Tecentriq (atezolizumab), Keytruda (pembrolizumab), and Tagrisso (osimertinib).

“In our study, we demonstrated that adding immune checkpoint inhibitors (ICIs) after surgery in patients with resectable NSCLC, who had previously received preoperative ICIs plus chemotherapy, did not improve survival outcomes,” Shaodong Hong, M.D., corresponding author, writes in an email to MHE. “Instead, it led to more side effects and increased costs,” she explains.

According to Hong, “Our data suggests that the current state of perioperative immunotherapy for NSCLC should be ‘less is more.’”

The new analysis was co-led by Hong and Li Zhang, M.D., both professors at the department of medical oncology at Sun Yat-sen University Cancer Center in Guangzhou, China. Their meta-analysis pooled data from 2,385 participants from pivotal neoadjuvant immunotherapy trials for resectable NSCLC including CheckMate816, IMpower010, PEARLS/KEYNOTE-091, and ADAURA. The goal of the meta-analysis was to compare the benefits and side effects of neoadjuvant-adjuvant anti-PD-1/PD-L1 therapy with neoadjuvant-only treatment.

Their findings revealed that adding PD-1/PD-L1 inhibitors in the adjuvant phase, along with neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy, did not show a significant improvement in event-free survival or overall survival for resectable NSCLC. Thus, these results suggest that adding adjuvant immunotherapy may not improve clinical outcomes.

However, due to the limitations of meta-analyses, the authors wrote in the conclusion of their paper that “future validation of these findings is warranted through head-to-head randomized clinical trials.”

Hong states: “Our findings suggest that future research should focus on personalized immunotherapy trials guided by specific biomarkers."