HK data: Durvalumab consolidation post-CRT improves PFS in stage III unresectable NSCLC

Durvalumab consolidation therapy following concurrent chemoradiotherapy (CRT) extends median progression-free survival (mPFS) in Hong Kong patients with unresectable stage III non-small-cell lung cancer (NSCLC), and also demonstrates a manageable safety profile, according to a real-world study at the Department of Oncology, Princess Margaret Hospital (PMH) conducted by Associate Consultant Dr Sheona Leung, Consultant Dr Fiona Lim, and Associate Consultant Dr Tracy Lau.

PACIFIC: From trial to real-world population
In the pivotal, global, phase III PACIFIC trial, 1 year of durvalumab consolidation therapy after CRT significantly improved both mPFS and median overall survival (mOS) in unresectable stage III NSCLC. (Table) [N Engl J Med 2017;377:1919- 1929; J Clin Oncol 2022;40:1301-1311]

The international, retrospective PACIFIC-R study reported 5-year survival outcomes of durvalumab consolidation in a large, diverse, real-world population. (Table) [J Thorac Oncol 2023;18:181-193; Girard N, et al, ELCC 2025, abstract 190P]

PMH’s real-world study: Superior mPFS with durvalumab
To examine the effectiveness andsafety of durvalumab in unresectablestage III NSCLC in a real-world tertiarycare setting in Hong Kong, the researchersconducted a retrospective studythat included 113 patients with stage IIINSCLC treated with CRT from December2017 to June 2023 in PMH. [Hong KongJ Radiol 2025;28:e91-e100]

A total of 51 patients received durvalumab plus CRT (median, age, 65 years; male, 76 percent), while 62 received CRT alone (median, age, 66.5 years; male, 84 percent). The median follow-up duration was 25.6 and 31.0 months, respectively. Baseline characteristics were similar between the two groups, except for a higher proportion of patients with no PD-L1 expression in the CRT alone vs durvalumab plus CRT cohort (48 vs 8 percent).

mPFS was 34.9 months with durvalumab plus CRT vs 10.5 months with CRT alone, demonstrating a statistically significant and clinically meaningful improvement with durvalumab plus CRT (log rank p=0.01). (Figure & Table)

mOS was numerically longer with durvalumab plus CRT (50.8 vs 41.5 months; p=0.32) vs CRT alone. (Table)

Notably, in PMH’s study, mPFS for both the durvalumab plus CRT and CRT alone cohorts were nearly double of those reported in the global PACIFIC trial. (Table) [J Clin Oncol 2022;40:1301-1311; Hong Kong J Radiol 2025;28:e91-e100]

“While variability in real-world follow-up may lead to underestimation of early progression, the prognostic advantages in our cohort study likely contributed [to the differences between our real-world data and clinical trial results],” explained the PMH researchers. “These included a higher proportion of patients with Eastern Cooperative Oncology Group performance status of 0 [88 percent vs 50 percent in PACIFIC] and more never-smokers [25 percent vs 9 percent in PACIFIC].” [Hong Kong J Radiol 2025;28:e91-e100; N Engl J Med 2017;377:1919-1929]

Favourable mPFS in EGFRm patients
In the small EGFR-mutated (EGFRm) subgroup of the PMH study, mPFS was longer with durvalumab plus CRT vs CRT alone (not reached vs 7.8 months), suggesting a potential benefit in these patients, none of whom had high PD-L1 expression. [Hong Kong J Radiol 2025;28:e91-e100]

“In the near future, both PD-L1 and EGFR statuses are expected to be critical in guiding treatment selection,” noted the researchers. “The recently published LAURA trial demonstrated highly encouraging mPFS benefits with adjuvant osimertinib vs placebo [39.1 vs 5.6 months] in EGFRm patients.” [Hong Kong J Radiol 2025;28:e91-e100; N Engl J Med 2024;391:585-597]

Manageable safety profile
In the PMH study, a higher incidence of any-grade pneumonitis was observed with durvalumab plus CRT vs CRT alone (31 vs 8 percent; p=0.002). “Overall, only 12 percent of patients discontinued durvalumab due to pneumonitis, similar to the reported 9.5 percent in the real-world PACIFIC-R study,” noted the researchers. [Hong Kong J Radiol 2025;28:e91-e100; J Thorac Oncol 2023;18:181-193]

Symptomatic pneumonitis tended to manifest in the first 3 months of therapy and was generally manageable.

Practical recommendations
Close monitoring during the first 3 months of treatment is recommended to facilitate early detection of and timely intervention for pneumonitis, as most patients (87.5 percent) experienced their first episode within the initial six biweekly cycles. [Hong Kong J Radiol 2025;28:e91-e100]

Most pneumonitis cases (approximately 80 percent) were grade 1 or 2 and responded to appropriate management strategies, such as corticosteroids, except for one case of grade 4 pneumonitis.

Receiver operating characteristic (ROC) analysis identified an optimal lung V_20Gy threshold of <22.76 percent for predicting pneumonitis, with a sensitivity of 0.92 and a specificity of 0.46.

“Practically, applying more stringent lung dose constraints while maintaining target coverage in radiotherapy planning for stage III NSCLC — which often involves bulky tumours — is challenging,” commented the researchers. “Lung V_20Gy should be kept as low as possible after balancing a reasonable target coverage, but its low specificity suggests it should be used alongside other clinical factors for individual risk assessment and planning.”

Key takeaways
Durvalumab following CRT is the standard of care in unresectable stage III NSCLC, with real-world survival outcomes in the PMH study (mPFS, 34.9 months; mOS, 50.8 months) exceeding those reported in the global phase III PACIFIC trial. [Hong Kong J Radiol 2025;28:e91-e100; J Clin Oncol 2022;40:1301-1311]

Evidence-based monitoring and keeping lung V_20Gy as low as possible are essential for optimizing treatment outcomes while minimizing toxicity to preserve patients’ quality of life.