Everett Vokes, MD
Approximately 30% to 40% of patients with non–small cell lung cancer (NSCLC) have stage III locally advanced disease at diagnosis.1,2
Stage III NSCLC is a highly heterogeneous disease that encompasses locally advanced primary tumors that have infiltrated mediastinal organs, involve mediastinal lymph nodes, or are larger than 7 cm.2,3
Patients are categorized as stage IIIA, IIIB, or IIIC, depending on tumor size and localization.3
No consensus exists on the best treatment approach for stage III NSCLC, but a combination of chemotherapy and radiotherapy is typically used.1
Currently, the 5-year survival rates for stage III NSCLC range from approximately 36% for stage IIIA to 26% for stage IIIB to 13% for stage IIIC.3
Although the past 2 decades saw an abundance of targeted agents and immunotherapies emerge for metastatic NSCLC, progress in locally advanced disease remained stagnant until recently.
In September 2017, at the annual European Society for Medical Oncology (ESMO) Congress, researchers presented positive data from a phase III trial of durvalumab (Imfinzi) in patients with stage III NSCLC.4,5
Durvalumab is an inhibitor of programmed cell death ligand-1 (PD-L1) approved in the United States for urothelial carcinoma. In an OncLive Peer Exchange®
, Everett E. Vokes, MD, moderated a panel of some of the world’s foremost experts on immunotherapy in lung cancer to discuss durvalumab and other emerging approaches for stage III NSCLC.
The Promise of Immunotherapy for Locally Advanced NSCLC
Immunotherapy has changed the paradigm for managing metastatic NSCLC. In took just a few years from the approval of checkpoint inhibitors as a second-line option to their integration into first-line management.
Naiyer A. Rizvi, MD, recalled the first patient with lung cancer he treated with the anti– PD-1 antibody nivolumab (Opdivo) in 2009; the patient had an adrenal mass that was so painful, he went to the emergency department for pain medication right after his first nivolumab infusion. “It’s 8 years later, and he still has no evidence of disease. That’s why I think we’re so excited about incorporating immunotherapy into our treatment,” Rizvi said.
The hope is that the success of immunotherapy in the metastatic setting will be repeated in the locally advanced setting. Although the approach for stage III locally advanced NSCLC has shifted from palliative to curative, Vokes said only one-quarter to one-third of patients survive 3 years. Rizvi said none of the approaches tried after chemoradiation—including consolidation chemotherapy or adjuvant vaccine therapy—has “moved the bar” for stage III patients.
Roy S. Herbst, MD, PhD, suggested that immunotherapy is poised to make a real difference for this population. Rizvi agreed, saying that many patients would be affected.
The PACIFIC Trial
For PACIFIC, an ongoing phase III trial, investigators have enrolled approximately 700 patients with untreated, unresectable stage III NSCLC.4
Participants underwent standard chemoradiotherapy before being randomly assigned to durvalumab or placebo at a 2:1 ratio.4
Interim data presented at the ESMO 2017 Congress and simultaneously published in the New England Journal of Medicine
showed an approximately 11-month difference in median progression-free survival (PFS) that favored the durvalumab arm (16.8 vs 5.6 months; stratified HR for disease progression or death, 0.52; 95% CI, 0.42-0.65; P
Compared with placebo, durvalumab was also associated with a higher rate of 1-year PFS (55.9% vs 35.3%, respectively), 18-month PFS (44.2% vs 27.0%), and overall response (28.4% vs 16.0%; P
Among patients who responded, significantly more in the durvalumab arm than in the placebo arm were still responding at 18 months (72.8% vs 46.8%). At the time of the interim analysis, data on overall survival (OS) were not yet mature.4
“[As far] as PFS goes, this is really a novel and impressive finding,” Vokes said. He added that the PFS data were unmatched by anything published for stage III NSCLC during at least the past 15 years.