Durvalumab improves overall survival in stage III NSCLC

The use of durvalumab after concurrent chemoradiation (cCRT) therapy reduces the risk of all-cause mortality by 32 percent in patients with unresectable stage III non-small-cell lung cancer (NSCLC), the PACIFIC trial has shown.

“The study results support cCRT followed by durvalumab as the new standard of care [SoC] in unresectable stage III NSCLC,” said principal investigator Dr Scott Antonia of Moffitt Cancer Center in Tampa, Florida, US. “Platinum-based cCRT has been the SoC in this setting. However, treatment outcomes have been poor, with only around 15 to 30 percent of patients being alive at 5 years.”

PACIFIC is a phase III study evaluating the use of durvalumab after platinum-based cCRT in patients with unresectable stage III NSCLC regardless of PD-L1 status whose disease had not progressed following cCRT. A total of 713 patients were randomized to receive durvalumab 10 mg/kg Q2W or placebo for up to 12 months. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

“The first interim analysis, performed in 2017, showed an improvement in median PFS of 11.2 months with durvalumab vs placebo,” said Antonia. [N Engl J Med 2017;377:1919-1929]

The present analysis, conducted after a median follow-up of 25.2 months, showed a significant OS improvement with durvalumab vs placebo (median, not reached vs 28.7 months; hazard ratio [HR], 0.68; 99.73 percent confidence interval [CI], 0.47 to 0.997; p=0.0025). The 12-month OS rate was 83.1 percent vs 75.3 percent, while the 24-month OS rate was 66.3 percent vs 55.6 percent. [N Engl J Med 2018, doi: 10.1056/NEJMoa1809697]

The updated PFS by blinded independent central review (BICR) remained favourable to durvalumab vs placebo (median, 17.2 months vs 5.6 months; HR, 0.51; 95 percent CI, 0.41 to 0.63)

“The PFS and OS benefits with durvalumab were observed across all prespecified subgroups,” reported Antonia. “However, our post-hoc analysis showed that the OS benefit with durvalumab was not demonstrated in patients with PD-L1 expression <1 percent.”

The median time to death or distant metastasis by BICR was longer with durvalumab vs placebo (28.3 months vs 16.2 months; HR, 0.53; 95 percent CI, 0.41 to 0.68). Compared with placebo, patients receiving durvalumab had fewer new lesions (22.5 percent vs 33.8 percent), with a lower incidence of new lung lesions (12.6 percent vs 18.6 percent), lymph node metastases (6.5 percent vs 11.4 percent) and brain metastases (6.3 percent vs 11.8 percent).

“The safety profile of durvalumab was consistent with that reported at the first interim analysis,” reported Antonia. “Serious adverse events were noted in 29.1 percent of patients receiving durvalumab and 23.1 percent of patients receiving placebo. Any-grade pneumonitis/radiation pneumonitis was reported in 33.9 percent and 24.8 percent of the patients, respectively, while the rate of grade 3/4 pneumonitis/radiation pneumonitis was similar between both groups [3.6 percent with durvalumab vs 3.0 percent with placebo].”

“PACIFIC is the first study to demonstrate a survival advantage after cCRT in patients with unresectable stage III NSCLC, supporting the PACIFIC regimen as the SoC in this setting,” concluded Antonia.