High-Dose CCRT Plus Durvalumab May Be Safe, Efficacious in Stage III NSCLC

The median time to tumor progression in was approximately 8 months (range, 5.7-14.7) in the 70 Gy and less than 70 Gy groups, with no significant difference in progression-free survival time found between the 2 groups.

High-dose concurrent chemoradiotherapy (CCRT) followed by durvalumab (Imfinzi) showed a favorable safety profile and may provide clinical benefits vs lower-dose CCRT in patients with stage III non–small cell lung cancer (NSCLC) with a PD-L1 expression of 1% or less, according to results from retrospective study published in Strahlentherapie und Onkologie.1

Data from the trial revealed that among all patients treated with CCRT and durvalumab (n = 39), tumor progression occurred in 35.9%. Among patients treated with 70 Gy of CCRT (n = 29), tumor progression occurred in 27.6%. Tumor progression occurred in 60% of those who received less than 70 Gy of CCRT (n = 10). Additionally, the median time to tumor progression in both groups was approximately 8 months (range, 5.7-14.7), with no significant difference in progression-free survival (PFS) time found between the 2 groups.

A total of 57.1% of tumor progression instances occurred following discontinuation or completion of durvalumab, including 75% of patients in the 70 Gy group and 33.3% among those who received less than 70 Gy. Seven patients died during the analysis, including 4 (40.0%) of those who received less than 70 Gy and 3 (10.3%) in the 70 Gy group. Furthermore, a favorable trend towards the 70 Gy arm in the incidence of death occurred, but it did not reach significance (P = .057).

“As long as clinicians adhere to established safety limits—especially in regard to low-dose lung volumes—we don’t expect to see an increased rate of pneumonitis [with a higher dose of radiation],” Felix Schragel, MD, specialist of pulmonology at University Hospital Krems of Karl Landsteiner University of Health Sciences in Krems, Austria, said in a news release on the study findings.2 “These results clearly show that administering a higher radiation dose to the tumor does not necessarily mean a higher risk of inflammatory [adverse] effects [AEs]—provided the treatment is well planned.”

The median overall survival (OS) in the 70 Gy and lower-dose arms was not reached and 31 months, respectively, reaching statistical significance (P = .028). The 6-, 12-, 24-, and 48-month OS rates in the 70 Gy group were 96.6%, 93.1%, 89.7%, and 89.7%. The respective OS rates in the lower-dose group were 90%, 80%, 70%, and 60%, respectively. Additionally, a univariate analysis for OS showed no difference among subgroups based on age, gender, histology, performance status, discontinuation of therapy, or pneumonitis incidence.

Patients with histologically or cytologically confirmed Union of International Cancer Control stage III NSCLC in the retrospective analysis received CCRT plus durvalumab across numerous hospitals within lower Austria between 2017 and 2023. Patients received 60 to 70 Gy of CCRT for at least 2 cycles, followed by 10 mg/kg of intravenous durvalumab biweekly for up to a year, after a mean of 14 days (range, 6-20) following CCRT. Those who did not experience any AEs following 6 cycles of durvalumab were administered a double dose every 4 weeks thereafter, with treatment occurring until disease progression, presence of an AE, or withdrawal of consent.

Among patients evaluated in the 70 Gy and less than 70 Gy groups, the median age was 64 years (IQR, 59.5-67.5) vs 62.5 years (IQR, 56.7-67.2), respectively. In each group, 62.1% vs 50% of patients were male, 96.6% vs 90% were former or current smokers, and 65.5% vs 50% had UICC stage IIIA disease. Respectively, 55.2% of the 70 Gy group vs 70% of the less than 70 Gy group had adenocarcinoma histology, 44.8% vs 80% had an ECOG performance status of 1, and 55.2% vs 50% had tumors located in the upper lobe.

The study end points included pneumonitis-free time, defined from the end of CCRT until the onset of pneumonitis of any cause; PFS, defined from the initiation of CCRT until disease progression; and OS, calculated following the day after CCRT using Kaplan-Meier estimation.

Pneumonitis developed in 15 (38.5%) patients, of whom 10 (34.5%) were from the 70 Gy dose group and 5 (50%) were from the less than 70 Gy group. The response with pneumonitis was 1.9 times as large in the less than 70 Gy group vs the 70 Gy group, and no significant difference in incidence or type of pneumonitis was observed between each group.

Of the 15 instances of pneumonitis, 14 were CTCAE grade 2, and 1 was CTCAE grade 3. Additionally, 1 instance of pneumonitis occurred following treatment discontinuation due to liver toxicity.

References

1. Schragel F, Matousek M, Resl C, et al. High radiation dose in chemoradiotherapy followed by immunotherapy with durvalumab in patients with stage III non-small cell lung cancer does not increase risk for pneumonitis. Strahlenther Onkol. Published online February 13, 2025. doi:10.1007/s00066-025-02369-0
2. High-dose radiotherapy: safe and promising for lung cancer. News release. Karl Landsteiner University of Health Sciences. May 13, 2025. Accessed May 27, 2025. https://tinyurl.com/3mjtzaye