Research Summary
Up to 35 percent of patients with completely resected non-small cell lung cancer (NSCLC) experience locoregional recurrence (LR), and many of these patients cannot undergo further surgery. Other treatment methods are thus necessary for this patient population. Patients with LR following complete resection are often treated with chemoradiotherapy, despite a lack of clinical recommendations. Durvalumab, a programmed death ligand 1 (PD‐L1)-targeting monoclonal antibody, has demonstrated efficacy in the treatment of unresectable Stage III NSCLC after concurrent CRT. Combination of durvalumab and CRT could improve survival outcomes among patients with LR following complete resection of NSCLC. Furuta et al1 thus compared the efficacy and safety of concurrent CRT followed by durvalumab (CRT-D) and CRT alone in this patient population. Their findings are summarized below.
Inclusion criteria were LR (recurrence only at local site or in regional lymph nodes) following complete resection with ND2a‐1 or higher level of lymph node dissection and CRT initiation between January 1, 2016, to December 31, 2020. Patients who received CRT alone following the approval of durvalumab were not included in the CRT alone group. The CRT regimen consisted of a minimum of two cycles of platinum-based chemotherapy and a total radiation dose of 54 to 66Gy. Patients in the CRT-D group received intravenous durvalumab 10mg/kg once every two weeks. Patients with small cell lung cancer (SCLC), combined SCLC and large cell neuroendocrine carcinoma, or failure to meet durvalumab eligibility criteria were excluded from this study.
A total of 196 patients were included for analysis, 121 in the CRT-D group and 75 in the CRT alone group. Inverse probability treatment weighting (IPWT) was used to adjust for confounders; following IWPT adjustment, there were 119 patients in the CRT-D group and 111 patients in the CRT alone group. Mean age was 66.7 years in the IWPT-adjusted CRT-D group and 65.4 years in the IWPT-adjusted CRT alone group. Adenocarcinoma was the most common histology in both groups after IWPT adjustment (CRT-D: 69.7%, CRT alone: 73.4%). In the IWPT-adjusted CRT-D group, epidermal growth factor receptor (EGFR) positivity was reported in 21.9 percent of patients, and EGFR negativity was reported in 68.1 percent. In the CRT alone group, 25.7 and 57.5 percent of patients had EGFR positivity and negativity, respectively. Pre-IWPT adjustment, PD-L1 status was known in 80.2 and 48 percent of patients in the CRT-D and CRT alone groups, respectively. Post-IWPT adjustment, PD-L1 expression was comparable between the CRT-D and CRT alone groups (≥50%: 26.1% and 26.5%; 1–49%: 31.9% and 34.3%; <1%: 22.7% and 18.2%).
The rate of disease progression was notably lower in the CRT-D group, compared to the CRT alone group, at the data cutoff date of June 30, 2023 (49.6% vs. 70.7%). Median follow-up was 27.3 and 31.6 months in the CRT-D and CRT alone groups, respectively.
The CRT-D group demonstrated significantly superior IWPT-adjusted progression-free survival (PFS) to the CRT alone group, with a median PFS 25.4 months versus 11.5 months, respectively. The 24- and 36-month PFS rates were 51 and 47 percent, respectively, in the CRT-D group. For those treated with CRT alone, the 24- and 36-month PFS rates were 21 and 16 percent, respectively. Additionally, median IWPT-adjusted time to first subsequent treatment was not reached in patients who received CRT-D, compared to 13.4 months for those who received CRT alone. Compared to the CRT alone group, the CRT-D group had significantly longer IWPT-adjusted overall survival (OS) as well. The 36-month OS rate was 80 percent in the CRT-D group versus 65 percent in the CRT alone group.
Subgroup analysis showed similar results, with a notable PFS benefit in the CRT-D group across all PD-L1 expression subgroups. In terms of OS, patients with PD-L1 expression of 50 percent or greater experienced significant benefits with the addition of durvalumab treatment, compared to CRT alone. OS also appeared to be significantly improved with durvalumab treatment in patients without EGFR mutations.
The overall rate of adverse events (AEs) was lower following initiation of durvalumab maintenance in the CRT-D group, compared to during CRT in the CRT-D group and during and after CRT in the CRT alone group; this difference was more pronounced in terms of Grade 3 or higher AEs, which were reported in only 10.7 percent of patients after durvalumab initiation in the CRT-D group, compared to 48.8 percent of patients during CRT in the CRT-D group and 53.7 percent of patients during and after CRT in the CRT alone group. Hyper- and hypothyroidism were more frequently reported in the CRT-D group, though there were no Grade 3 or higher cases. Febrile neutropenia was more frequent in the CRT alone group, with eight of nine cases being Grade 3 or higher.
Limitations included potential selection and informational biases. Differences in the analytical periods and differences in the year of treatment initiation were also potential limitations. The small number of patients included in subgroup analyses was another limitation.
This study demonstrated that the addition of durvalumab following CRT improved PFS and OS outcomes in patients with completely resected NSCLC who developed LR, compared to CRT alone, and had an acceptable safety profile.
Reference:
- Furuta M, Horinouchi H, Yokota I, et al. Durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small-cell lung cancer (NEJ056). Cancer Sci. 2024;115(11):3705–3717.