PACIFIC: Practice-Changing Trial in Stage III Unresectable NSCLC

December 2018 Vol 9, No 12

The PD-L1 inhibitor durvalumab showed an overall survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in the phase 3 PACIFIC trial.

Durvalumab improved survival by 32% versus placebo in patients who had not progressed on concurrent chemoradiotherapy. This is the first time a study has demonstrated a survival advantage, and results suggest that durvalumab will be a new standard of care in this setting.

Results from the trial were greeted with enthusiasm at the IASLC 19th World Conference on Lung Cancer and were published simultaneously in The New England Journal of Medicine.

The survival analysis showed a statistically significant and clinically meaningful difference in overall survival for durvalumab versus placebo in patients with unresectable stage III NSCLC.

“We saw improvements in progression-free survival, time to distant metastases, and emergence of new lesions with durvalumab, and the drug was well tolerated. This is the first study in many years to support a survival advantage for unresectable stage III NSCLC with no progression following chemoradiotherapy,” said lead author Scott J. Antonia, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

PACIFIC is a positive trial with a 32% improvement in survival, and is a new standard of care, according to Everett Vokes, MD, chair of the Department of Medicine at University of Chicago, IL, who was formal discussant of the trial.

About 15% to 30% of patients with locally advanced unresectable stage III NSCLC are cured with conventional chemotherapy and radiotherapy with curative intent.

“We’ve been stuck with those numbers for decades. Last year, we saw an 11.2-month improvement in progression-free survival with durvalumab in the PACIFIC trial. Today we see improved overall survival,” Dr Antonia stated.

The randomized, placebo-controlled, phase 3 PACIFIC trial was conducted at 235 investigative sites in 26 countries and enrolled 713 patients who did not progress after chemoradiotherapy for unresectable stage III NSCLC. Patients were randomized 2:1 to durvalumab or placebo 1 to 42 days after radiation and treated every 2 weeks for up to 12 months or disease progression.

“We took all comers regardless of PD-L1 expression,” Dr Antonia told the audience.

Baseline characteristics were well balanced between the 2 treatment arms. The 12-month overall survival rate was 83.1% for durvalumab versus 75.3% for placebo. The 24-month overall survival rate was 66.3% versus 55.6%, respectively. Median overall survival was not reached in the durvalumab group and was 28.7 months for placebo, representing a 32% improvement in survival for the PD-L1 inhibitor (P = .0025).

Updated analysis showed median progression-free survival of 16.8 months with durvalumab versus 5.6 months with placebo (P <.001), an 11.2-month improvement.

PD-L1 testing was obtained prior to chemoradiotherapy. More than one-third of patients in PACIFIC had unknown PD-L1 status. Patients with the lowest level of PD-L1 expression (<1%) did not benefit from durvalumab.

The time to death or distant metastasis was longer in the durvalumab group: median of 28.3 months versus 16.2 months for placebo.

No new safety signals emerged during the trial. Grade 3/4 adverse events of any cause occurred in 30.5% of the durvalumab group and 26.1% of the placebo group. Discontinuations due to adverse events were reported in 15.4% and 9.8%, respectively. The most frequent events leading to discontinuation were pneumonitis (4.8% of the durvalumab group and 2.6% of placebo patients).

Serious adverse events were reported in 29.1% of the durvalumab group and 23.1% of the placebo group. Death due to adverse events occurred in 4.4% and 6.4%, respectively.

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