Real-World Data Confirm Safety, Efficacy of Durvalumab After CRT in NSCLC

Consolidation therapy with durvalumab after chemoradiotherapy (CRT) was effective and well-tolerated in a preplanned analysis of the real-world PACIFIC-R study (NCT03798535) of patients with unresectable stage III non–small-cell lung cancer (NSCLC). Results from the retrospective analysis were published in the Journal of Thoracic Oncology.

Historically, platinum-based chemotherapy with concurrent radiotherapy (cCRT) was the standard-of-care for unresectable, stage III NSCLC. Post-treatment, active surveillance was the norm until the phase 3 PACIFIC trial (NCT02125461) found that consolidation therapy with durvalumab, a programmed cell death-ligand 1 (PD-L1) inhibitor, improved overall survival (OS) and progression-free survival (PFS) versus a placebo.

Based on PACIFIC trial data, durvalumab was the first drug to be approved for consolidation therapy in unresectable, stage III NSCLC with no disease progression after CRT. The observational PACIFIC-R study of patients who started durvalumab as part of an early access program (EAP) is ongoing, but the results of a pre-specified analysis provide real-world data on the regimen’s safety and efficacy at approximately 2 years of follow-up.

As of November 30, 2022, the analysis included 1399 patients across 290 hospitals in 11 predominantly European countries. The median follow-up time was 23.5 months, with 3 patients lost to follow-up. Most patients (94.7%) had stage III NSCLC at the time of diagnosis, and the rest had relapsed to stage III from earlier disease stages. The median patient age at EAP entry in the full analysis was 66 years, the majority were male (67.6%), and most were current or former smokers (92.1%).

Among the 1399 patients in the overall patient population, 737 (52.7%) had either experienced disease progression or had died without documentation of progression at the time of the database cutoff for the pre-planned analysis. The median real-world PFS (rwPFS) was 21.7 months in the overall cohort. At 12 months and 24 months of follow-up, 62.2% and 48.2% of patients, respectively, were estimated to be alive and without disease progression. Median overall survival (OS) was not reached, but 71.2% of patients were estimated to be alive at 24 months.

Of patients in the overall cohort considered to have completed treatment (47.1%), the median time to discontinuation was 11.9 months. The most common reasons for treatment discontinuation before completion were disease progression and adverse events (AEs) in 26.9% and 16.7% of patients, respectively.

The most common prior CRT treatment was cCRT (76.6%), while 14.4% of patients received sequential CRT (sCRT). Patients who received cCRT had numerically longer rwPFS than patients who received sCRT, and receiving cisplatin during CRT led to longer rwPFS than carboplatin in this cohort. In the United States, the approved label excludes use of durvalumab after sCRT, while the European Medicines Agency allows either cCRT or sCRT. Those who initiated durvalumab more than 42 days after radiotherapy cessation had lower rwPFS than patients who started durvalumab earlier.

Among patients with PD-L1 expression of at least 1%, rwPFS was numerically longer compared with those with PD-L1 expression less than 1%. Patients with EGFR mutations had numerically shorter rwPFS compared with the overall cohort, while patients with known KRAS mutations had numerically longer rwPFS than the overall cohort.

Taken together, the data from the PACIFIC-R trial thus far confirm the effectiveness of the PACIFIC regimen of durvalumab after CRT, and these findings align other real-world studies of durvalumab as post-CRT consolidation therapy in unresectable, stage III NSCLC. These findings support use of durvalumab as the standard of care for this patient population in real-world clinical settings.

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 Onc. Published online October 25, 2022. doi:10.1016/j.jtho.2022.10.003