Durvalumab Results Spark Hope for Progress in Advanced NSCLC

Christin L. Melton, ELS
Published: Tuesday, Apr 16, 2019
Mark A. Socinski, MD
Mark A. Socinski, MD
After a signiciant drought in progress in treating stage III non–small cell lung cancer (NSCLC), the thoracic oncology community is decidedly excited by the recently published results of the phase III PACIFIC trial (NCT02125461).1 The PACIFIC investigators found that administering the immune checkpoint inhibitor (ICI) durvalumab (Imfinzi) to patients with stage III unresectable NSCLC after concurrent chemoradiotherapy (CCRT) significantly enhanced overall survival (OS) with an acceptable increase in toxicity.1

For more than a decade, CCRT has been the standard of care for fit patients with unresectable locally advanced (LA) NSCLC,2-4 and currently, between 30% and 50% of newly diagnosed cases of LA-NSCLC are unresectable.5 Although multiple clinical trials have associated CCRT with greater clinical benefit than radiotherapy alone or sequential radiotherapy and chemotherapy, prognosis after CCRT has remained dismal.2,3,6 Approximately 10% of patients die within 6 months of treatment,4 OS ranges from 18 to 28 months, and the estimated 5-year OS rate is 15% to 25%.6,7

Efforts to improve outcomes by increasing the radiotherapy dose, administering a targeted agent with CCRT or as consolidation therapy, or replacing second-generation chemotherapy agents with newer ones all failed to improve survival.1,6,8 Surgical resection for stage III disease was also unsuccessful at prolonging survival.2 Further, some attempted approaches significantly increased the risk of morbidity or mortality compared with standard CCRT.2,5,8

During an OncLive Peer Exchange® discussion, moderator Mark A. Socinski, MD, and other lung cancer experts from across the United States discussed what, in this context, the PACIFIC trial results mean for practicing oncologists and their patients. The results “have really changed the standard of care in stage III disease,” Socinski said.

The PACIFIC Trial

In recent years, the FDA has approved several ICIs that target PD-1 or PD-L1 for stage IV NSCLC based on clinical trial results that have shown strong efficacy in some patients.6 The activity of PD-1/PD-L1 inhibitors in metastatic NSCLC, coupled with preclinical studies that suggested CCRT amplifies PD-L1 expression in tumors, generated interest in evaluating these ICIs for unresectable LA disease.1 Preliminary data from the phase III investigation of durvalumab in patients with unresectable stage III NSCLC whose disease had not progressed after CCRT led the FDA to approve the anti–PD-L1 monoclonal antibody for this patient population in early 2018.9

Trial Design and Efficacy

“The [PACIFIC] trial was actually a placebocontrolled trial of durvalumab delivered every 2 weeks in a group of patients who had inoperable stage III disease and had completed standard CCRT,” said Mohammad Jahanzeb, MD, describing the study’s design. Adults (median age, 64 years) were recruited at 235 sites in 26 countries spanning every continent except Antarctica.1 Jahanzeb said two-thirds of the approximately 700 patients were randomly assigned to durvalumab (n = 473) and the rest to placebo (n = 236) within 42 days of their last radiation dose.1 Durvalumab was administered intravenously at a dose of 10 mg/kg until disease progression or study withdrawal for up to 12 months.1 He said PACIFIC used a blinded panel to assess OS and progression-free survival (PFS), which were the trial’s primary endpoints.1

Jahanzeb noted that median PFS was almost 3 times longer in the durvalumab arm than in the placebo arm (17.2 vs 5.6 months, respectively; HR for disease progression or death, 0.51; 95% CI, 0.41-0.63).1 He explained that although median PFS of 5.6 months for the control arm appears short, efficacy endpoints were calculated from the time of randomization.1 “When you take that into account, the control arm is not as bad as we think, and it’s believable,” he said.


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Online CME Activities
TitleExpiration DateCME Credits
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
Community Practice Connections™: Working Group for Changing Standards in EGFR-Mutated Lung Cancers: Real-World Applications of the Evidence for NursesJun 29, 20191.5
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