Durvalumab plus sequential or concurrent chemoradiotherapy (CRT) is effective and well tolerated in unresectable, stage III non-small cell lung cancer (NSCLC), according to real-world results published in the Journal of Thoracic Oncology.

Researchers found that real-world progression-free survival (rwPFS) outcomes were better among patients who received concurrent CRT rather than sequential CRT. Similarly, rwPFS outcomes were better among patients with higher PD-L1 expression. 

This trial, PACIFIC-R (ClinicalTrials.gov Identifier: NCT03798535), included 1399 patients with unresectable, advanced NSCLC. They had a median age of 66.0 (range, 26-88) years, 67.5% were men, and 92.1% were current or former smokers. About half of patients (51.3%) had stage IIIB/C disease at initial diagnosis, 64.0% had nonsquamous subtype at stage III diagnosis, and 18.0% had PD-L1 expression below 1%.


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Patients had started durvalumab treatment via an early-access program between September 2017 and December 2018. They could receive either concurrent CRT or sequential CRT, and they could continue durvalumab (10 mg/kg every 2 weeks) until disease progression. 

Overall, 47.1% of patients completed more than 12 months of durvalumab treatment. The median time to treatment discontinuation was 11.9 months. The most common reasons for discontinuation were disease progression (26.9%) and adverse events (AEs; 16.7%).

The study’s primary endpoints were rwPFS and overall survival. The median rwPFS was 21.7 months. The 12-month rwPFS rate was 62.2%, and the 24-month rwPFS rate was 48.2%.

The median rwPFS was 22.4 months for patients with PD-L1 expression of 1% or higher and 15.6 months for those with PD-L1 expression below 1%. The median rwPFS was 23.7 months for patients with stage IIIA disease and 19.2 months for those with stage IIIB/C disease. 

The median rwPFS was 25.3 months for patients with nonsquamous disease and 14.6 months for those with squamous disease. The median rwPFS was 23.7 months with concurrent CRT and 19.3 months with sequential CRT.

The median overall survival was not reached. At the data cutoff, 30.7% of patients had died. An estimated 71.2% of patients were alive at 24 months.

AEs leading to treatment interruption occurred in 11.2% of patients. AEs leading to discontinuation occurred in 16.5%. The most common AEs were pneumonitis or interstitial lung disease (5.2% leading to interruption and 9.5% leading to discontinuation); endocrinopathies (1.3% and 0.7%, respectively); hepatitis or transaminase increase (0.7% and 1.2%, respectively); and diarrhea, colitis, and/or intestinal perforation (1.1% for both).

“The findings from PACIFIC-R demonstrate that consolidation therapy with durvalumab following definitive CRT is well tolerated and effective in this curative-intent setting,” the researchers wrote. “Outcomes were broadly consistent with the PACIFIC trial, although the median rwPFS reported for PACIFIC-R was longer than the median PFS reported with durvalumab in PACIFIC; limitations associated with assessing disease progression in the real-world setting likely caused an overestimation of rwPFS.” 

Disclosures: PACIFIC-R was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Girard N, Bar J, Garrido P, et al. Treatment characteristics and real-world progression-free survival in patients with unresectable stage III NSCLC who received durvalumab after chemoradiotherapy: Findings from the PACIFIC-R study. J Thorac Oncol. Published online October 25, 2022. doi:10.1016/j.jtho.2022.10.003