medwireNews: Neoadjuvant treatment with the PD-1 inhibitor nivolumab shows promising activity in patients with untreated surgically resectable early non-small-cell lung cancer (NSCLC), with few side effects, US researchers report.
Furthermore, Drew Pardoll (Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland) and colleagues observed increases in tumor-specific T-cell clones in peripheral blood following treatment, indicating that neoadjuvant PD-1 blockade “could enhance the systemic priming of antitumor T cells, thereby potentially eliminating micrometastatic cancer that otherwise might cause postsurgical relapse.”
The pilot study included 21 adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC (62% adenocarcinoma) who received two preoperative doses of intravenous nivolumab (3 mg/kg every 2 weeks), and underwent surgery approximately 4 weeks after the first dose.
The researchers report in The New England Journal of Medicine that the treatment had “an acceptable side-effect profile,” with no new toxic effects reported and only one adverse event of grade 3 or higher (pneumonia).
There were no surgical delays due to adverse events, and 20 of the 21 tumors were completely resected.
Recurrence-free survival was 80% at a median of 12 months and 73% at 18 months, with the median duration not yet reached.
Just under half (45%) of the 20 patients with completely resected tumors had a major pathologic response, defined as no more than 10% viable cells on hematoxylin and eosin staining following resection. By contrast, only two patients had a partial radiographic response.
The team found that patients who had a major pathologic response had a significantly higher pretreatment tumor mutational burden than those without a major response, but responses occurred in both PD-L1–positive and PD-L1–negative tumors.
An analysis of paired pre- and post-treatment blood samples from nine patients showed that the frequency of tumor-specific T-cell clones increased in eight of these patients following treatment. Moreover, a number of the clones detected were not present in the peripheral blood prior to treatment.
Pardoll et al conclude that their findings “represent pathological evidence supporting the possibility that some patients may derive clinical benefit from immunotherapy without initial radiographic tumor shrinkage and that this process occurs because of immune-cell infiltration into the tumor, rather than true tumor growth.”
They add: “Larger studies are needed to determine the most effective duration of neoadjuvant therapy and the best predictive biomarkers of response and to correlate the pathological response resulting from neoadjuvant immunotherapy with overall survival.”
The study findings were also presented at the American Association for Cancer Research Annual Meeting 2018, held in Chicago, Illinois, USA.
By Laura Cowen
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