Multimodality treatment in synchronous oligometastatic NSCLC: Analysis of the ETOP CHESS trial

Objective: To evaluate the addition of immunotherapy and metastasis-directed stereotactic body radiotherapy (SBRT) to induction chemotherapy followed by definitive local therapy of the locoregional primary tumour in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC). Methods: CHESS is a prospective, international, multicentre, single-arm, phase II trial evaluating the efficacy and safety of combined chemotherapy (carboplatin plus paclitaxel), immune checkpoint inhibition (durvalumab) and metastasis-directed SBRT, followed by definitive radiotherapy or surgery of the primary tumour (if no disease progression at the 3-month restaging) and maintenance durvalumab for maximum one year in patients with synchronous oligometastatic NSCLC. The primary endpoint was one-year progression-free survival, aiming to an improvement from 25% to 50%. Results: A total of 49 patients were enrolled from 11/2019 to 07/2022. Up to 05/2023, the median follow-up was 22 months. Of 47 patients starting treatment, 10 progressed and 2 died before restaging, while 35 proceeded to definitive therapy of the locoregional primary (11 surgery, 24 radiotherapy). Among the first 42 evaluable patients, 14 (33%; ≥17 required) reached one year without progression, and the null hypothesis could not be rejected. The one-year overall survival rate for all patients was 74.9% (95% CI: 60.0%–84.9%). Treatment-related grade ≥ 3 adverse events were reported in 34% of patients, with no grade 5 event. Conclusion: The CHESS trial did not meet its primary endpoint. However, the favourable safety profile and promising overall survival provided the basis for further intensification of induction systemic therapy (addition of tremelimumab in a subsequent study cohort; CHESS–Cohort 2).