ANN ARBOR, MI – While adjuvant durvalumab after definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) is well-tolerated in clinical trials, that is not always the case in the real-world, according to a new VA study.
University of Michigan and Ann Arbor, MI, VA Healthcare System researchers and colleagues suggested that pneumonitis rates outside of clinical trials remain poorly defined with CRT followed by durvalumab.
The study team, which also included the VA Los Angeles Healthcare System, sought to describe the influence of durvalumab on pneumonitis rates among a large cohort of patients with stage III NSCLC. Results were published in the International Journal of Radiation Oncology, Biology & Physics.1
To do that, researchers studied patients with stage III NSCLC treated within the VHA from 2015 to 2021 who received concurrent CRT alone or with adjuvant durvalumab. For purposes of the study, pneumonitis was defined as worsening respiratory symptoms with radiographic changes within two years of CRT and graded events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Results indicated that, among 1,994 patients (989 CRT alone, 1005 CRT followed by adjuvant durvalumab), the 2-year incidence of grade 2 or higher pneumonitis was 13.9% for CRT alone vs 22.1% for CRT plus durvalumab (unadjusted P < .001).
“On multivariable analysis, durvalumab was associated with higher risk of grade 2 pneumonitis (hazard ratio, 1.45; 95% CI, 1.09-1.93; P = .012) but not grade 3 to 5 pneumonitis (P = .2). Grade 3 pneumonitis conferred worse overall survival (hazard ratio, 2.51; 95% CI, 2.06-3.05; P < .001) but grade 2 pneumonitis did not (P = .4),” the authors wrote.
The researchers concluded that adjuvant durvalumab use was associated with an increased risk of low-grade but not higher-grade pneumonitis. “Reassuringly, low-grade pneumonitis did not increase mortality risk,” they advised. “We observed increased rates of high-grade pneumonitis relative to clinical trials; the reasons for this require further study.”
A recent study in the Journal of Thoracic Oncology pointed out that durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. Yale University School of Medicine researchers and international colleagues suggested, however, that the optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remained unknown.2
The multi-institutional international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. The focus was on estimating real-world progression-free survival (rwPFS, primary endpoint) and overall survival (OS, secondary endpoint).
Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 received observation alone. Baseline characteristics were similar across the three cohorts.
With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (Inter-quartile range [IQR]: NR-NR) and was 5.5 (IQR:2.4-10.8) months with durvalumab.
“After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those in the durvalumab or observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p<0.001 for both comparisons),” according to the researchers. “There was no difference in rwPFS between durvalumab and the observation cohort. No significant difference in OS across the 3 cohorts was detected, possibly due to the limited follow-up.”
The study team reported that any grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors (TKIs). Of these, 14 (38%) patients developed trAEs including 5 pneumonitis (14%; 2 [5.4%] grade ≥3) and 5 diarrhea (14%; 1 [2.7%] grade ≥3).
“This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with significantly longer rwPFS than durvalumab or observation,” the authors concluded. “No unanticipated safety signals were observed with consolidation osimertinib.”
- Edwards DM, Sankar K, Alseri A, Jiang R, et. Al. Pneumonitis After Chemoradiotherapy and Adjuvant Durvalumab in Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2023 Oct 2:S0360-3016(23)07971-3. doi: 10.1016/j.ijrobp.2023.09.050. Epub ahead of print. PMID: 37793573.
- Nassar AH, Kim SY, Aredo JV, Feng J, et. Al. Consolidation Osimertinib versus Durvalumab versus Observation following Concurrent Chemoradiation in Unresectable EGFR-Mutant Non-Small-Cell Lung Cancer: A Multicenter Retrospective Cohort Study. J Thorac Oncol. 2024 Jan 24:S1556-0864(24)00032-7. doi: 10.1016/j.jtho.2024.01.012. Epub ahead of print. PMID: 38278303.
