Session Item

The addition of adjuvant durvalumab to chemoradiotherapy (CRT) in  locally advanced NSCLC resulted in a significant improvement of OS and PFS. Several single centre studies reported on an increase in adverse events, in particular in radiation pneumonitis (RP). However, large cohort studies presenting real-world data are lacking. The aim of this study was to investigate the incidence of RP after CRT with adjuvant durvalumab immunotherapy in patients with locally advanced NSCLC.

The study population was composed of all patients with NSCLC that completed CRT with curative intent between February 2013 and October 2020. From 2018 on, adjuvant durvalumab immunotherapy was administered in patients with locally advanced stage (II-III) disease, a WHO performance of 0-1 and without disease progression after completion of CRT. Patient and tumour characteristics, dosimetric RT data, chemotherapy and immunotherapy data together with RP data (CTCAE v4.0, scored up to 9 months after CRT), were prospectively collected as part of our standard follow up program. 

A total of 318 patients were enrolled, of which 97 (30.5%) received adjuvant durvalumab. Baseline patient and tumour characteristics did not differ between the two groups. Patients in the durvalumab group received proton therapy more often. A significant increase in the incidence of grade ≥2 RP in patients receiving durvalumab compared to CRT only was observed (17.5% vs. 8.6%; HR: 2.27, 95%CI: 1.17-4.41, p=0.016). In the first six months after ending CRT, both groups had equal cumulative RP incidences. Interestingly, after these six months, patients receiving adjuvant durvalumab developed RP more frequently compared to patients treated with only CRT (Figure 1). In multivariable logistic regression analysis, adjuvant treatment with durvalumab was significantly associated with a higher incidence of grade ≥2 RP (HR 2.57, 95%CI: 1.24-5.33, p=0.011). Also, the risk of RP increased with higher MLD (HR 1.16, 95%CI: 1.04-1.29, p=0.009). Treatment with adjuvant durvalumab results in an additional probability on developing grade ≥2 RP, especially when the MLD is high (Figure 2). The 2-years OS in the durvalumab group was 80.8% compared to 57.5% after CRT only (p=0.027). Patients treated with durvalumab had a decreased hazard on death in the first 2 years after completing CRT (HR 0.42, 95%CI: 0.18–0.95, p=0.038).

Treatment with adjuvant durvalumab significantly increased the incidence of grade ≥2 RP in this cohort of real-world NSCLC patients. Furthermore, the time patients are prone to develop grade ≥2 RP after ending CRT was longer in patients receiving adjuvant durvalumab compared to patients treated with CRT only.