Neoadjuvant nivolumab in early NSCLC: Flexing its therapeutic muscles beyond advanced cancer treatment

  • Date: 08 Oct 2016

Programmed death-1 (PD-1) is a checkpoint cell-surface protein receptor that protects against lymphocyte-mediated autoimmunity and inflammation in the normal state, but can facilitate immune evasion by tumour cells. Nivolumab is an anti-PD-1 monoclonal antibody approved in 2015 for the treatment of metastatic non-small-cell lung cancer (NSCLC) that has progressed after platinum-based therapy. Nivolumab is also indicated for the treatment of advanced melanoma, advanced renal cell carcinoma and relapsed/progressed classical Hodgkin lymphoma, highlighting its broad clinical utility.

Yesterday, Dr Patrick Forde of Johns Hopkins University, Baltimore, Maryland, USA reported potentially ground-breaking results from a study of neoadjuvant nivolumab in patients with early NSCLC (resectable stage I–IIIA) the first instance of its use outside advanced cancer treatment (Abstract LBA41_PR). Two doses of nivolumab were administered to 18 patients prior to lung surgery: seven patients demonstrated a major pathologic response (<10% residual tumour evident), one patient had complete pathologic response and 13 patients had stable disease. Importantly, nivolumab treatment was well tolerated with no significant safety concerns. Grade 3–4 treatment-emergent adverse events were reported in one patient and led to nivolumab discontinuation. There was no delay in surgery in any patient, indicating that the benefits of this neoadjuvant therapy outweighed the potential risks. This proof-of-concept study is a breakthrough, hinting at the very real possibility of substantially improved outcomes in early NSCLC; however, whether tumour shrinkage will ultimately translate into better survival is still to be proven.

Dr Forde added that, “Following these initial results we are expanding the study. One cohort will receive a third dose of nivolumab pre operatively and the other will receive the combination of nivolumab and ipilimumab pre-operatively.”

This article appeared in the Saturday edition of the Daily Reporter