Highlights from

ESMO 2020

European Society for Medical Oncology Congress 2020

Virtual 19 - 21 September 2020

Preoperative immunotherapy in early stage NSCLC safe and feasible

Both the phase 2 IONESCO and the phase 2 PRINCEPS trial evaluated adjuvant immunotherapy in patients with early-stage resectable non-small cell lung cancer (NSCLC).Both trials concluded that neoadjuvant immunotherapy in patients with early-stage NSCLC is feasible and safe, and does not delay or compromises surgery.

Theoretically, neoadjuvant immunotherapy has several advantages over adjuvant immunotherapy. Higher antigen load and neoantigen release from untreated tumours could better prime the immune system. Before surgery the host immune system is fit. The tumour is less heterogeneous as it has not got the change to undergo clonal evolution. And, neoadjuvant therapy provides de opportunity to evaluate the response of the tumour to the immunotherapy.

In the IONESCO trial, 50 patients with early-stage NSCLC were included (IB ≥4 cm – IIIA, non N2). The patients were treated with 3 courses of de PD-L1 inhibitor durvalumab (750 mg, day 1, 15, 29). Surgery was scheduled between day 2 and 14 after the last infusion [1]. In the PRINCEPS trial, 30 patients were included (I > 2cm - IIIA, non N2). Patients received just one injection of the PD-L1 inhibitor atezolizumab (1,200 mg). Surgery was scheduled in week 4 after the atezolizumab treatment [2].

In IONESCO, 46 patients received neoadjuvant treatment of whom 43 went into surgery without any delay (1 patient had progression, 1 pleural invasion, 1 oesophageal invasion). In PRINCEPS all patients had their surgery as scheduled. Overall, 41/46 patients in IONESCO (89.1%) had a complete surgical resection (R0); 4 (8.7%) showed a partial radiological response (RECIST 1.1), and 36 (78.3%) showed stable disease; 8 patients (18.6%) had a major pathological response (<10% residual viable tumour cells). In PRINCEPS, 29/30 (97%) patients had a complete surgical resection; 2 (7%) patients showed a partial radiological response (RECIST 1.1), and 27 (93%) had stable disease (1 additional stable disease pending central review); 4 (14%) patients had a major pathological response (<10% residual viable tumour cells) and 12 patients (41%) had a pathological response (<50% viable tumour cells). There was no correlation between radiological and pathological response. However, there was a correlation between pathological response and PD-L1 expression at baseline.

After one year, 89.1% of the patients in IONESCO were still alive and 78.2% had not relapsed. However, because of an excess in 90-day postoperative mortality (4 (9%) deaths), inclusion was stopped. These deaths were not related to treatment with durvalumab but resulted from post-operative complications most likely due to comorbidities. Adjuvant durvalumab was well tolerated.

  1. Wislez M, et al. Neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC): Preliminary results from a multicenter study (IFCT-1601 IONESCO). ESMO 2020 Virtual Meeting, abstract 1214O.
  2. Besse B, et al. Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): results from the phase II PRINCEPS trial. ESMO 2020 Virtual Meeting, abstract 1215O.

Top image: @ iStockPhoto: luismmolina

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.