Immune checkpoint inhibitor (ICI) therapy has revolutionized the cancer treatment landscape providing treatment options to patients with advanced cancers. Non-small cell lung cancer (NSCLC) represents one of the hard-to-treat malignancies for which ICIs have presented new treatment options in recent years.
In 2018, clinical trial data highlighted neoadjuvant programmed-cell death protein-1 (PD-1) blockade as a safe and feasible treatment for NSCLC. PD-1 blockade, nivolumab, when administered before surgery, induced responses in almost half of the tumors and conferred no significant side effects. While this study showed great promise for patients with NSCLC, as a pilot study (NCT02259621), oncologists could not fully access the efficacy of PD-1 blockade or the long-term impacts of the drug.
Fast forward to February 2023, the same team of researchers published updated results in Clinical Cancer Research, providing valuable clinical outcomes from the trial originally reported on five years earlier. The authors note that their new study delivers the longest follow-up data for neoadjuvant PD-1 blockade to date.
The study included 21 patients with Stage I–IIIA NSCLC. The cohort consisted of eleven women and ten men at an average age of 67. Most (86%) of the participants reported a history of smoking. The trial eligibility guidelines allowed some patients (26%) to receive adjuvant chemotherapy in addition to nivolumab. At the time of analysis, participants had been monitored for an average of 63 months.
The study revealed that 80% of the participants remained alive. This high survival rate is notable, as the survival of patients with NSCLC receiving surgery alone ranges from 36 – 68%. Further, 60% of the participants achieved five-year recurrence-free survival. This means that 60% of the patients had not experienced tumor regression survival five years after surgery.
The study also evaluated major pathological response (MPR) in the resected lung tissue following surgery. In patients achieving MPR, less than 10% of the resected tissue contains residual tumor, indicating that the neoadjuvant nivolumab administered before surgery effectively killed tumor cells. The researchers reported nine patients with MPR, and eight of these patients remained alive and disease-free five years post-treatment. One patient with MPR died from a non-cancer-related cause. Seven of the eleven patients without MPR still achieved five-year survival; however, recurrence occurred more often in these patients.
Similar to the observation in the original study, no severe side effects resulted from the therapeutic regimen, and no patients in the study had to delay surgery due to side effects.
The authors acknowledge a limitation of the study as the small number of patients. However, despite this caveat, the study demonstrates the potential long-lasting benefits of PD-1 blockade administered before surgery.
Sources: NEJM, Clin Cancer Res, J Thorac Oncol, Lancet Oncol
