Neoadjuvant immunotherapy in non-small cell lung cancer: the sooner the better?

Abstract

Recently, Forde et al. reported in the New England Journal of Medicine a pilot study in which two neoadjuvant doses of the PD-1 inhibitor nivolumab were administered in a preoperative fashion to 21 patients with untreated, surgically resectable early (stage I–IIIA) non-small cell lung cancer (NSCLC) (1). Surgery was performed 4 weeks after the first dose of nivolumab. In addition to an acceptable toxicity profile, which did not cause delays in surgery, nivolumab induced a major pathological response in 9 of 20 resected tumors (45%). Pathological responses were observed in patients presenting PD-L1 positive and negative tumors and, interestingly, they correlated with pretreatment tumor mutational burden. The authors found that the number of T-cell clones observed in the tumor and peripheral blood increased following nivolumab in eight of nine patients. Remarkably, the authors described one patient presenting a complete response in which neoantigen-specific T-cell clones from the primary tumor rapidly expanded in peripheral blood following treatment. Moreover, some of these clones were not detected before treatment with nivolumab, thus suggesting that PD-1 blockade induced their expansion.