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. 2025 Feb 13:64:267-275.
doi: 10.2340/1651-226X.2025.42384.

Rising incidence of radiation pneumonitis after adjuvant durvalumab in NSCLC patients treated with concurrent chemoradiotherapy

Rutger H Stoffers  1 , Anne G H Niezink  2 , Olga Chouvalova  2 , Jan F Ubbels  2 , Marleen Woltman-van Iersel  2 , T Jeroen N Hiltermann  3 , Lucie B M Hijmering-Kappelle  3 , Gea Douma  4 , Sander M De Hosson  5 , John W G Van Putten  6 , Friso T Zandberg  7 , Lisanne V Van Dijk  2 , Johannes A Langendijk  2 , Robin Wijsman  2
Affiliations

Rising incidence of radiation pneumonitis after adjuvant durvalumab in NSCLC patients treated with concurrent chemoradiotherapy

Rutger H Stoffers et al. Acta Oncol. .

Abstract

Background and purpose: Adding adjuvant durvalumab to chemoradiotherapy (CRT) improves overall survival (OS) rates in locally advanced Non-Small-Cell Lung Cancer (NSCLC). However, recent data suggests that this new modality increases the incidence of radiation pneumonitis (RP). The aim of this study was to test the hypothesis that the incidence of RP after CRT and adjuvant durvalumab was higher than after CRT alone among patients with locally advanced NSCLC.

Materials and methods: The study population comprised all patients with NSCLC who completed CRT with curative intent between February 2013 and October 2020. From 2018 on, adjuvant durvalumab was administered in selected patients after completion of CRT. Patient and treatment data together with RP data (CTCAEv4.0, scored up to 9 months after CRT), were prospectively collected as part of our standard follow-up program.

Results: A total of 284 patients were included, of which 90 (30.5%) received adjuvant durvalumab. Incidence of grade ≥2 RP increased in patients receiving durvalumab compared to CRT only (17.8% vs. 8.8%; p < 0.05), especially between 6 to 9 months after completing CRT. Adjuvant durvalumab and mean lung dose (MLD) were associated with a higher incidence of grade ≥2 RP (odds ratio [OR]: 2.43 and 1.14, respectively; p < 0.05). Current smoking was found to be a protective factor (OR: 0.38; p < 0.05).

Interpretation: Adjuvant durvalumab significantly increased the incidence of grade ≥2 RP in this real-world cohort of NSCLC patients. Patients receiving adjuvant durvalumab remain prone to develop grade ≥2 RP longer after completing CRT compared to patients treated with CRT only.

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Conflict of interest statement

The department of Radiation Oncology of the UMCG has research collaborations with IBA, Philips, Mirada, RaySearch, Siemens, Elekta and Leoni.

T Jeroen N Hiltermann has collaborations with Roche, BMS, Astra Zeneca, MSD, Pfizer, GSK, Novartis, Merck Serono and Amgen.

Figures

Figure 1
Figure 1
Inclusion tree for our cohort. *Patients were excluded in the listed order. **6 thymoma/12 metastasis other pathology/5 other pathology not considered NSCLC or SCLC. ***13 post-operative RT, 8 trimodality treatment and 13 recurrent disease.
Figure 2
Figure 2
Plot for the incidence of grade ≥ 2 radiation pneumonitis 9 months after ending CRT. The total incidence of grade ≥ 2 radiation pneumonitis was 17.8% in the durvalumab group and 8.8% in the CRT only group. *p < 0.05.
Figure 3
Figure 3
Hazard ratio curves for risk of developing grade ≥2 pneumonitis per week after CRT for adjuvant treatment with durvalumab compared with CRT only. The crossed marks represent the censored data. Analysis was performed at a maximum for 9 months after ending CRT.
Figure 4
Figure 4
Normal Tissue Complication Probability (NTCP) curves of the probability of developing grade > 2 RP for patients treated with adjuvant durvalumab and smoking status with increasing MLD. [NTCP = 1 / (1 + e- (−4.168 + 0.121*MLD + 0.888*durvalumab treatment + 0.978*smoking status))]. These NTCP values are a representation of our cohort and must be interpreted as such.
Figure 5
Figure 5
Kaplan–Meier curves of overall survival for adjuvant treatment with durvalumab compared with CRT only. The crossed marks represent the censored data.
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References

    1. Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. . Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181–90. 10.1200/jco.2009.26.2543 - DOI - PubMed
    1. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. . Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342–50. 10.1056/NEJMoa1809697 - DOI - PubMed
    1. Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. . Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301–11. 10.1200/jco.21.01308 - DOI - PMC - PubMed
    1. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. . Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29. 10.1056/NEJMoa1709937 - DOI - PubMed
    1. Vansteenkiste JF, Naidoo J, Faivre-Finn C, Özgüroğlu M, Villegas A, Daniel D, et al. . Symptomatic pneumonitis with durvalumab after concurrent chemoradiotherapy in unresectable stage III NSCLC. JTO Clin Res Rep. 2024;5(3):100638. 10.1016/j.jtocrr.2024.100638 - DOI - PMC - PubMed

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