AACR 2018: Pilot Study of Neoadjuvant Nivolumab in Resectable NSCLC


Key Points

  • Major pathologic response was observed in 45% of resected tumors.
  • Response was associated with higher tumor mutational burden.

In a pilot study reported at the 2018 American Association for Cancer Research (AACR) Annual Meeting (Abstract CT079) and in The New England Journal of Medicine by Forde et al, neoadjuvant nivolumab therapy was found to be feasible and active in patients with resectable non–small cell lung cancer (NSCLC).

Study Details and Results

In the study—performed at Johns Hopkins University and Memorial Sloan Kettering Cancer Center—21 eligible patients with untreated resectable stage I, II, or IIIA NSCLC received nivolumab at 3 mg/kg every 2 weeks with surgery planned approximately 4 weeks after the first dose.

In total, 20 of 21 patients received 2 doses of nivolumab. The median interval between the second dose of nivolumab and surgery was 18 days (range = 11–29 days). Treatment-related adverse events of any grade occurred in 5 patients (23%), with only 1 event being grade ≥ 3.

Of 21 tumors removed, 20 were completely resected. Major pathologic response occurred in 9 (45%) of 20 resected tumors; complete pathologic response was found in the primary tumor in 3 patients, with 1 of them having residual tumor in hilar lymph nodes. Responses were observed in both programmed cell death ligand 1 (PD-L1)-positive and PD-L1–negative tumors. At a median of 12 months of postoperative follow-up (range = 0.8–19.7 months), 16 (80%) of 20 patients who had undergone resection were alive and recurrence-free.

Genomic and Immune Response Findings

Among 11 patients with complete resection and tumor samples that had undergone whole-exome sequencing, mean tumor mutational burden was significantly higher in those with vs without major pathologic response (311 vs 74, P = .01). The number of sequence alterations was inversely associated with the percentage of residual tumor. No significant correlation was found between mutational burden and PD-L1 expression.

The number of T-cell clones found in both tumor and peripheral blood increased after nivolumab treatment in 8 of 9 evaluated patients. Mutation-associated neoantigen-specific T-cell clones from a tumor in a patient with pathologic complete response exhibited rapid expansion in peripheral blood at 2 to 4 weeks after treatment, with some of these clones not being detected prior to nivolumab administration.

The investigators concluded, “Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood.”

The study was funded by the Cancer Research Institute–Stand Up 2 Cancer, Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Bristol-Myers Squibb, International Immuno-Oncology Network, and others. 

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