Nivolumab found to be a safe and feasible option in early stage NSCLC
- This was the first trial investigating programmed death (PD)-1 inhibitor nivolumab in early stage lung cancer
- Nivolumab was tested as a neoadjuvant to surgery in patients with non-small cell lung cancer (NSCLC)
- The study found nivolumab to be both safe and feasible for early stage NSCLC
Results presented at this year’s European Society for Medical Oncology Congress explored, for the first time, the use of nivolumab for stage I-IIIA NSCLC. The data, presented by Dr Patrick Forde, Assistant Professor of Oncology, Johns Hopkins, Baltimore, US, confirmed that its use in this setting was found to be both safe and feasible.
Stage I-III NSCLC currently carries a poor prognosis, and patients tend to see only a modest benefit from using adjuvant chemotherapy. Drugs blocking the PD-1 ligand signalling pathway, however, have shown significant improvements in overall survival for some patients with advanced NSCLC. These factors formed the rationale for Dr Forde and his team’s investigation into using nivolumab, first line, preoperatively for NSCLC.
The primary objectives were the safety and feasibility of nivolumab, which was administered twice, once at day 14 and 28. Treatment was deemed feasible if surgery was not delayed as a result.
The study met its primary objective, Dr Forde explains; “this early stage study shows that neoadjuvant therapy with two doses of nivolumab is safe and feasible in lung cancer”. All of the 18 patients included in the trial attended surgery on time. No significant safety signals were identified.
The opportunity to carry out correlative analyses on [resected] specimens is huge, and will drive other studies in the future.”
Dr Patrick Forde, Johns Hopkins, Baltimore, US
The use of an immunotherapeutic neoadjuvant to surgery provides a number of valuable exploratory advantages. The method enables investigators to carry out correlative analyses, to assess pathological response, and has the potential for enhancing systemic immunity against occult metastases.
Exploratory endpoints of the study included correlatives in the blood and tumour, pathological response, recurrence-free survival and overall survival.
At the time of resection, 39% (n=7) of patients exhibited a pathological down-staging, compared to their stage prior to therapy with nivolumab. One patient had a complete pathological response (<10% remaining viable tumour cells). 22% (n=4) of patients had a radiographic response to the treatment, based on RECIST criteria (version 1.1).
A number of analyses are still ongoing, studying the genomics, immunohistochemistry, T-cell receptor clonality and tumour infiltrating leukocytes.
When asked if this research could be applied to other cancer types, Dr Forde commented “It potentially does; the neoadjuvant model is a great opportunity to study immunotherapy in particular, in that you can isolate the immune cells and lymphocytes from the specimen.”
Other studies are currently investigating the use of nivolumab for early stage kidney cancer, prostate cancer and melanoma – this could extend to other cancer types in the near future.
The study has provided a foundation for future work in the area; Dr Forde elaborated, “the plan is to expand to give three doses [of nivolumab], and also to look at combining nivolumab with other immune checkpoint antibodies prior to surgery in early stage disease”.
verall, carrying out these exploratory analyses could have an impact on prospective work. Dr Forde believes that “the opportunity to carry out correlative analyses on these specimens is huge, and will drive other studies in the future”. Larger follow-up studies are on the horizon.
Based on Forde P, Smith K et al. Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small cell lung cancer (LBA41_PR). Presented on Friday 7 October 2016.
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